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Enrico CLINI

Professore Ordinario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2024 - Efficacy of respiratory muscle training in the immediate postoperative period of cardiac surgery: A systematic review and meta-analysis. [Articolo su rivista]
Nema de Aquino, Tarcísio; Paulo Prado, João; Crisafulli, Ernesto; Clini, Enrico; Galdino, Giovane
abstract

Introduction: This study aimed to evaluate the efficacy of respiratory muscle training during the immediate postoperative period of cardiac surgery on respiratory muscle strength, pulmonary function, functional capacity, and length of hospital stay. Methods: This is a systematic review and meta-analysis. A comprehensive search on PubMed, Excerpta Medica Database (or Embase), Cumulative Index of Nursing and Allied Health Literature (or CINAHL), Latin American and Caribbean Health Sciences Literature (or LILACS), Scientific Electronic Library Online (or SciELO), Physiotherapy Evidence Database (or PEDro), and Cochrane Central Register of Controlled Trials databases was performed. A combination of free-text words and indexed terms referring to cardiac surgery, coronary artery bypass grafting, respiratory muscle training, and clinical trials was used. A total of 792 studies were identified; after careful selection, six studies were evaluated. Results: The studies found significant improvement after inspiratory muscle training (IMT) (n = 165, 95% confidence interval [CI] 9.68, 21.99) and expiratory muscle training (EMT) (n = 135, 95% CI 8.59, 27.07) of maximal inspiratory pressure and maximal expiratory pressure, respectively. Also, IMT increased significantly (95% CI 19.59, 349.82, n = 85) the tidal volume. However, no differences were found in the peak expiratory flow, functional capacity, and length of hospital stay after EMT and IMT. Conclusion: IMT and EMT demonstrated efficacy in improving respiratory muscle strength during the immediate postoperative period of cardiac surgery. There was no evidence indicating the efficacy of IMT for pulmonary function and length of hospital stay and the efficacy of EMT for functional capacity.

2024 - Home non-invasive ventilation in severe COPD: in whom does it work and how? [Articolo su rivista]
Raveling, Tim; Vonk, Judith; Hill, Nicholas; Gay, Peter; Casanova, Ciro; Clini, Enrico; Köhnlein, Thomas; Márquez-Martin, Eduardo; Schneeberger, Tessa; Murphy, Patrick; Struik, Fransien; Kerstjens, Huib; Duiverman, Marieke; Wijkstra, Peter
abstract

Background: Not all hypercapnic COPD patients benefit from home NIV, and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify ‘responders’ to NIV, denoted by a beneficial effect of NIV on PaCO2, health-related quality of life (HRQL) and survival, and investigated whether NIV achieves its beneficial effect through an improved PaCO2. Methods: We used individual patient data from previous published trials collated for a systematic review. Linear mixed effect models were conducted to compare the effect of NIV on PaCO2, HRQL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in PaCO2. Findings: Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (PS <14 vs ≥14cmH2O) and with lower adherence (<5 vs ≥5h) had less improvement in PaCO2 (mean difference (MD) -0.30kPa, p<0.001 and -0.29kPa, p<0.001 respectively) and HRQL (standardised MD 0.10, p=0.002 and 0.11, p=0.02 respectively), but this effect did not persist to survival. PaCO2 improved more in patients with severe dyspnoea (MD -0.30, p=0.02), and HRQL improved only in participants with <3 exacerbations (SMD 0.52, p=0.03). The mediation analysis showed that the effect on HRQL is mediated partially (23%) by change in PaCO2. Interpretation: Higher PS and daily usage of NIV result in greater improvements in PaCO2 and HRQL. Importantly, we demonstrated that the beneficial effect of home NIV on HRQL is partially mediated through reduced PaCO2.

2024 - Impact of frailty on symptom burden in Chronic Obstructive Pulmonary Disease [Articolo su rivista]
Verduri, Alessia; Clini, Enrico; Carter, Ben; Hewitt, Jonathan
abstract

Chronic Obstructive Pulmonary Disease (COPD), the sixth leading cause of death in the United States in 2022 and the third leading cause of death in England and Wales in 2022, is associated with high symptom burden, particularly dyspnea. Frailty is a complex clinical syndrome associ-ated with an increased vulnerability to adverse health outcomes. The aim of this review was to explore the current evidence of the influence of frailty on symptoms in patients with a confirmed diagnosis of COPD according to GOLD guidelines. Fourteen studies report a positive association between frailty and symptoms, including dyspnea, assessed with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) scale. Data were analysed in a pooled a ran-dom-effects meta-analysis Mean Difference (MD). There was an association between COPD pa-tients living with frailty and increased score of CAT versus COPD patients without frailty [pooled SMD, 1.79 (95% CI 0.72-2.87); I2 =99%]. Lower association was found between frailty and dyspnea measured by mMRC scale versus COPD patients without frailty [pooled SMD, 1.91 (95% CI 1.15-2.66); I2 =98%]. The prevalence of frailty ranged from 8.8% to 82%, pre-frailty from 30.4% to 73.7% in people living with COPD. The available evidence supports the role of frailty in worsen-ing symptom burden in COPD patients living with frailty. The review shows that frailty is com-mon in patients with COPD. Future research is needed to have further details related to the data from CAT to improve our knowledge of the frailty impact in this population.

2024 - Proteomics Analysis of Formalin-Fixed Paraffine-Embedded Tissue Reveals Key Proteins Related to Lung Dysfunction in Idiopathic Pulmonary Fibrosis. [Articolo su rivista]
Samarelli, ANNA VALERIA; Tonelli, Roberto; Raineri, Giulia; Bruzzi, Giulia; Andrisani, Dario; Gozzi, Filippo; Marchioni, Alessandro; Costantini, Matteo; Fabbiani, Luca; Genovese, Filippo; Pinetti, Diego; Manicardi, Linda; Castaniere, Ivana; Masciale, Valentina; Aramini, Beatrice; Tabbi', Luca; Rizzato, Simone; Bettelli, Stefania; Manfredini, Samantha; Dominici, Massimo; Clini, Enrico; Cerri, Stefania
abstract

Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. We further determined the protein expression according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. After the pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor β (TGF‐β) signaling pathways strongly associated with IPF onset and progression. Five proteins were significantly over-expressed in the lung of IPF patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLco<55) compared to controls; these were lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan (OGN) that might play a key role in the fibrogenic processes. Our work showed that the analysis of FFPE samples was able to identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or involved in the immune landscape of lung cancer, thus making possible common mechanisms between lung carcinogenesis and fibrosis progression, two pathological conditions at risk for each other in the real life.

2024 - Pulmonary fibrosis and lung carcinogenesis: do myofibroblasts and cancer-associated fibroblasts share a common identity? [Articolo su rivista]
Totero Daniela, De; Barisione, Emanuela; Clini, Enrico
abstract

Not available

2024 - When sarcoidosis hits down: a case of prostatic sarcoidosis. [Articolo su rivista]
Moretti, Antonio; Bruzzi, Giulia; Andrisani, Dario; Gozzi, Filippo; Costantini, Matteo; Tonelli, Roberto; Clini, Enrico; Cerri, Stefania
abstract

A 69-year-old North African male with established diagnosis of sarcoidosis underwent a stereotactic prostate biopsy with fusion technique. At the histological analysis, non-necrotizing microgranulomas were highlighted in 2 samples, while the immunohistochemical staining resulted negative for CK903/p63/racemase. To the best of our knowledge, only 16 cases of prostatic sarcoidosis have been reported in literature. With this case report we describe an incidental diagnosis of prostatic involvement of sarcoidotic disease and briefly review and discuss the available literature on the topic.

2023 - Accuracy of nasal pressure swing to predict failure of high flow nasal oxygen in patients with acute hypoxemic respiratory failure [Articolo su rivista]
Tonelli, Roberto; Cortegiani, Andrea; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Bruzzi, Giulia; Busani, Stefano; Ball, Lorenzo; Clini, Enrico; Marchioni, Alessandro
abstract

Not available

2023 - Association Between Pulmonary Aspergillosis And Cytomegalovirus Reactivation In Critically Ill Covid-19 Patients: A Prospective Observational Cohort Study. [Articolo su rivista]
Caciagli, Valeria; Coloretti, Irene; Talamonti, Marta; Farinelli, Carlotta; Gatto, Ilenia; Biagioni, Emanuela; Sarti, Mario; Franceschini, Erica; Meschiari, Marianna; Mussini, Cristina; Tonelli, Roberto; Clini, Enrico; Girardis, Massimo; Busani, Stefano
abstract

COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to ex-plore the association between CAPA development and the incidence and prognosis of cytomegalo-virus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive criti-cally ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from February 25, 2020, to May 8, 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associ-ated with CAPA and CMV reactivation and the association between CMV recurrence and mor-tality were estimated using adjusted Cox proportional hazard regression models. CAPA oc-curred in 96 patients (16,6%) of the 579 patients analyzed. Among the CAPA population, 40 (41,7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p=0.166). The CAPA+CMV group had a longer ICU stay, few-er ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p=0.011). In critically ill COVID-19 pa-tients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immuno-suppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.

2023 - Bronchiectasis as long-term complication of acute fire smoke inhalation? [Articolo su rivista]
Rizzato, Simone; Tacconi, Matteo; Andrisani, Dario; Luppi, Fabrizio; Clini, Enrico; Cerri, Stefania
abstract

In this letter to editor, we discuss the occurrence of radiological and clinical evidence of bronchiectasis syndrome three years after acute exposure to fire smoke in a Caucasian non-smoker asthmatic patient.

2023 - COPD: Providing the Right Treatment for the Right Patient at the Right Time. [Articolo su rivista]
Agusti, Alvar; Ambrosino, Nicolino; Blackstock, Felicity; Bourbeau, Jean; Casaburi, Richard; Celli, Bartolome; Crouch, Rebecca; Dal Negro, Roberto; Dreher, Michael; Garvey, Christine; Gerardi, Daniel; Goldstein, Roger; Hanania, Nicola; Holland, Anne E.; Kaur, Antarpreet; Lareau, Suzanne; Lindenauer, Peter; Mannino, David; Make, Barry; Maltais, François; Marciniuk, Jeffrey; Meek, Paula; Morgan, Mike; Pepin, Jean-Louis; Reardon, Jane; Rochester, Carolyn; Singh, Sally; Spruit, Martijn; Steiner, Michael; Troosters, Thierry; Vitacca, Michele; Clini, Enrico; Jardim, Jose; Nici, Linda; Raskin, Jonathan; Zuwallack., Richard
abstract

COPD is a chronic respiratory disease with prominent systemic consequences and comorbidities. While historically it has been characterized by airflow limitation, we now understand it as a multi-component disease with many clinical phenotypes, systemic manifestations, and associated co-morbidities. With this new and broader concept in mind, standard treatment of the respiratory disease with bronchodilators, antiinflammatory medications, and exacerbation management interventions may fall short in optimizing outcomes. This narrative review emphasizes the holistic treatment of the COPD patient, based on newly developed concepts of its pathogenesis, nature, and necessary comprehensive approaches to its therapy. The material in its four sections: 1) New Concepts of COPD; 2) Enhancing Outcomes in COPD; 3) Non-Pharmacologic Management of COPD; and 4) Optimizing Delivery of Care for COPD is not mean to be provide an exhaustive review of all aspects of COPD; rather, it presents what experts in the field consider novel and important in providing the right treatment for the right patient at the right time.

2023 - Chronic Airways Assessment Test: psychometric properties in patients with asthma and/or COPD [Articolo su rivista]
Tomaszewski, E. L.; Atkinson, M. J.; Janson, C.; Karlsson, N.; Make, B.; Price, D.; Reddel, H. K.; Vogelmeier, C. F.; Mullerova, H.; Jones, P. W.; del Olmo, R.; Anderson, G.; Rabahi, M.; Mcivor, A.; Sadatsafavi, M.; Weinreich, U.; Burgel, P. -R.; Devouassoux, G.; Papi, A.; Inoue, H.; Rendon, A.; van den Berge, M.; Beasley, R.; Garcia-Navarro, A. A.; Faner, R.; Rivera, J. O.; Janson, C.; Bilinska-Izydorczyk, M.; Fageras, M.; Fihn-Wikander, T.; Franzen, S.; Keen, C.; Ostridge, K.; Chalmers, J.; Harrison, T.; Pavord, I.; Price, D.; Azim, A.; Belton, L.; Ble, F. -X.; Erhard, C.; Gairy, K.; Hughes, R.; Lassi, G.; Mullerova, H.; Rapsomaniki, E.; Scott, I. C.; Chipps, B.; Make, B.; Christenson, S.; Tomaszewski, E.; del Olmo, R.; Benhabib, G.; Ruiz, X. B.; Lisanti, R. E.; Marino, G.; Mattarucco, W.; Nogueira, J.; Parody, M.; Pascale, P.; Rodriguez, P.; Silva, D.; Svetliza, G.; Victorio, C. F.; Rolon, R. W.; Yanez, A.; Baines, S.; Bowler, S.; Bremner, P.; Bull, S.; Carroll, P.; Chaalan, M.; Farah, C.; Hammerschlag, G.; Hancock, K.; Harrington, Z.; Katsoulotos, G.; Kim, J.; Langton, D.; Lee, D.; Peters, M.; Prassad, L.; Sajkov, D.; Santiago, F.; Simpson, F. G.; Tai, S.; Thomas, P.; Wark, P.; Rabahi, M.; Cancado, J. E. D.; Cunha, T.; Lima, M.; Cardoso, A. P.; Fitzgerald, J. M.; Mcivor, A.; Anees, S.; Bertley, J.; Bell, A.; Cheema, A.; Chouinard, G.; Csanadi, M.; Dhar, A.; Dhillon, R.; Kanawaty, D.; Kelly, A.; Killorn, W.; Landry, D.; Luton, R.; Mandhane, P.; Pek, B.; Petrella, R.; Stollery, D.; Wang, C.; Chen, M.; Chen, Y.; Gu, W.; Hui, K. M. C.; Li, M.; Li, S.; Lijun, M.; Qin, G.; Song, W.; Tan, W.; Tang, Y.; Wang, T.; Wen, F.; Wu, F.; Xiang, P. C.; Xiao, Z.; Xiong, S.; Yang, J.; Yang, J.; Zhang, C.; Zhang, M.; Zhang, P.; Zhang, W.; Zheng, X.; Zhu, D.; Bueno, C. M.; Grimaldos, F. B.; Arboleda, A. C.; de Salazar, D. M.; Weinreich, U.; Bendstrup, E.; Hilberg, O.; Kjellerup, C.; Burgel, P. -R.; Devouassoux, G.; Raherison, C.; Bonniaud, P.; Brun, O.; Chouaid, C.; Couturaud, F.; de Blic, J.; Debieuvre, D.; Delsart, D.; Demaegdt, A.; Demoly, P.; Deschildre, A.; Egron, C.; Falchero, L.; Goupil, F.; Kessler, R.; Le Roux, P.; Mabire, P.; Mahay, G.; Martinez, S.; Melloni, B.; Moreau, L.; Riviere, E.; Roux-Claude, P.; Soulier, M.; Vignal, G.; Yaici, A.; Bals, R.; Aries, S. P.; Beck, E.; Deimling, A.; Feimer, J.; Grimm-Sachs, V.; Growth, G.; Herth, F.; Hoheisel, G.; Kanniess, F.; Lienert, T.; Mronga, S.; Reinhardt, J.; Schlenska, C.; Stolpe, C.; Teber, I.; Timmermann, H.; Ulrich, T.; Velling, P.; Wehgartner-Winkler, S.; Welling, J.; Winkelmann, E. -J.; Papi, A.; Barbetta, C.; Braido, F.; Cardaci, V.; Clini, E. M.; Costantino, M. T.; Cuttitta, G.; di Gioacchino, M.; Fois, A.; Foschino-Barbaro, M. P.; Gammeri, E.; Inchingolo, R.; Lavorini, F.; Molino, A.; Nucera, E.; Patella, V.; Pesci, A.; Ricciardolo, F.; Rogliani, P.; Sarzani, R.; Vancheri, C.; Vincenti, R.; Inoue, H.; Endo, T.; Fujita, M.; Hara, Y.; Horiguchi, T.; Hosoi, K.; Ide, Y.; Inomata, M.; Inoue, K.; Inoue, S.; Kato, M.; Kawasaki, M.; Kawayama, T.; Kita, T.; Kobayashi, K.; Koto, H.; Nishi, K.; Saito, J.; Shimizu, Y.; Shirai, T.; Sugihara, N.; Takahashi, K. -I.; Tashimo, H.; Tomii, K.; Yamada, T.; Yanai, M.; Rendon, A.; Javier, R. C.; Peregrina, A. D.; Corzo, M. F.; Gonzalez, E. M.; Ramirez-Venegas, A.; van den Berge, M.; Boersma, W.; Djamin, R. S.; Eijsvogel, M.; Franssen, F.; Goosens, M.; Graat-Verboom, L.; in't Veen, J.; Janssen, R.; Kuppens, K.; van de Ven, M.; Bakke, P.; Brunstad, O. P.; Einvik, G.; Hoines, K. J.; Khusrawi, A.; Oien, T.; Yoon, H. J.; Chang, Y. -S.; Cho, Y. J.; Hwang, Y. I.; Kim, W. J.; Koh, Y. -I.; Lee, B. -J.; Lee, K. -H.; Lee, S. -P.; Lee, Y. C.; Lim, S. Y.; Min, K. H.; Oh, Y. -M.; Park, C. -S.; Park, H. -S.; Park, H. -W.; Rhee, C. K.; Yoon, H. -K.; Garcia-Navarro, A. A.; Rivera, J. O.; Andujar, R.; Anoro, L.; Garcia, M. B.; Mozo, P. C.; Campos, S.; Maldonado, F. C.; Martinez, M. C.; Serrano, C. C.; Casanova, L. C.; Corbacho, D.; Del Campo Matias, F.; Echave-Sustaeta
abstract

Background: No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). Methods: The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. Results: CAAT items were internally consistent (Cronbach’s alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson’s correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4–0.7) to strongly (> 0.7) with other PRO measures and weakly (< 0.4) with spirometry measures. Conclusions: CAAT scores appear to reflect the same health impairment across asthma and COPD, making the CAAT an appropriate PRO instrument for patients with asthma and/or COPD. Its brevity makes it suitable for use in clinical studies and routine clinical practice. Trial registration: NCT02760329.

2023 - Covid-19, a new possible mimicker of interstitial lung disease related to primary Sjögren’s syndrome: a case report. [Articolo su rivista]
Laneri, Alessia; Cerri, Stefania; DELLA CASA, Giovanni; Moretti, Antonio; Manfredi, Andreina; Sebastiani, Marco; Clini, Enrico; Salvarani, Carlo
abstract

Introduction: Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases (CTD). Case report: In 2018, a 52-year-old woman, was diagnosed with pSS. The patient complained of no respiratory symptoms and a chest x-Ray was normal. During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest HRCT showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFT) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist didn’t allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A wait and see approach was decided, monitoring clinical conditions, PFTs and chest HRCT over time. Only 2 years after the hospitalization, a slight improvement of clinical symptoms was reported; PFT also improved; a follow-up HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations. Discussion: In the above-reported case report, 3 differential diagnoses were possible: a COVID-19 related ILD, a pre-existing pSS-ILD or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations rapidly disappeared after about 2 years.

2023 - Critical COVID-19 Patients Through First, Second And Third Wave: Retrospective Observational Study Comparing Outcomes In ICU. [Articolo su rivista]
Coloretti, Irene; Farinelli, Carlotta; Biagioni, Emanuela; Gatto, Ilenia; Munari, Elena; Dall'Ara, Lorenzo; Busani, Stefano; Meschiari, Marianna; Tonelli, Roberto; Mussini, Cristina; Guaraldi, Giovanni; Cossarizza, Andrea; Clini, Enrico; Girardis, Massimo
abstract

Introduction- The time-course of the COVID-19 pandemic was characterized by subsequent waves identified by peaks of Intensive Care Unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods- Outcomes were evaluated in consecutive adult COVID19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation. Results- Overall, 428 patients were included in the analysis: 102, 169 and 157 patients in the first, second and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other 2 waves (p>0.05). A higher number of ICU and hospital free days at day 90 was found in the third wave when compared to the other 2 waves (p=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (p=0.002). The adjusted Cox model showed no difference in the Hazard Ratio for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (p=0.044). Conclusions - With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves.

2023 - Do all critically ill patients with COVID-19 disease benefit from adding tocilizumab to glucocorticoids? A retrospective cohort study. [Articolo su rivista]
Mussini, Cristina; Cozzi-Lepri, Alessandro; Meschiari, Marianna; Franceschini, Erica; Jole Burastero, Giulia; Faltoni, Matteo; Franceschi, Giacomo; Iadisernia, Vittorio; Volpi, Sara; Dessilani, Andrea; Gozzi, Licia; Conti, Jacopo; DEL MONTE, Martina; Milic, Jovana; Borghi, Vanni; Tonelli, Roberto; Brugioni, Lucio; Romagnoli, Elisa; Pietrangelo, Antonello; Corradini, Elena; Girardis, Massimo; Busani, Stefano; Cossarizza, Andrea; Clini, Enrico; Guaraldi, Giovanni
abstract

2023 - Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate order. [Articolo su rivista]
Tonelli, Roberto; Fantini, Riccardo; Bruzzi, Giulia; Tabbì, Luca; Cortegiani, Andrea; Crimi, Claudia; Pisani, Lara; Moretti, Antonio; Guidotti, Federico; Rizzato, Simone; Puggioni, Daniele; Tacconi, Matteo; Bellesia, Gianluca; Ragnoli, Beatrice; Castaniere, Ivana; Marchioni, Alessandro; Clini, Enrico
abstract

Background- High flow nasal oxygen (HFNO) is recommended as a first line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF. Methods- Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔPes), clinical variables before and after 2 hours of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔPes values and the relative change in breathing effort and clinical variables after 2 hours of HFNO was explored. Results- Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔPes (12 vs 16 cmH2O, p<0.0001), respiratory rate (RR) (22 VS 28 bpm, p<0.0001), PaO2/FiO2 (133 VS 126 mmHg, p<0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p<0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p<0.0001) and BORG (1 VS 4, p<000.1). Patients with baseline ΔPes below 20 cmH2O where those who improved all the explored variables, while patients with baseline ΔPes above 30 cmH2O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔPes values and after 2 hours of HFNO (R2= 0.9, p<0.0001). ΔPes change 2 hours after HFNO significantly correlated with change in BORG (p<0.0001), ROX index (p<0.0001), HACOR score (p<0.001) and RR (p<0.001). Conclusions- In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

2023 - Endoscopic closure with double stenting and autologous fascia lata graft of large tracheo-esophageal fistula [Articolo su rivista]
Mattioli, Francesco; Serafini, Edoardo; Andreani, Alessandro; Cappiello, Gaia Francesca; Marchioni, Daniele; Pinelli, Massimo; Tonelli, Roberto; Clini, Enrico; Marchioni, Alessandro
abstract

Introduction: Radiotherapy and esophageal stenting are usually employed to manage esophageal localization of distant cancer. However, they are also related to the occurrence of an increased risk of tracheoesophageal fistula. Tracheoesophageal fistula management in these patients involves dealing with poor general conditions and short-term prognosis.This paper presents the first case in literature of bronchoscopic fistula closure through an autologous fascia lata graft placement between two stents. Case report and aim: A 67-years-old male patient was diagnosed with pulmonary squamous cell carcinoma in the inferior lobe of the left lung with mediastinal lymph node metastasis. After a multidisciplinary discussion, bronchoscopic repair of tracheoesophageal fistula with autologous fascia lata was decided without the removal of the esophageal stent due to the high risk on the esophagus possibly related to such a procedure. Oral feeding was progressively introduced without the development of aspiration symptoms. Videofluoroscopy and esophagogastroduodenoscopy were performed at seven months showing no signs of tracheoesophageal fistula patency. Conclusion: This technique might represent a low risks viable option for patients unsuitable for open surgical approaches.

2023 - Frailty and its influence on mortality and morbidity in COPD: A systematic review and Meta-Analysis. [Articolo su rivista]
Verduri, Alessia; Carter, Ben; Laraman, James; Rice, Ceara; Clini, Enrico; Maskell, Nick; Hewitt., Jonathan
abstract

Background: Frailty increases vulnerability to adverse outcomes. Long-term conditions increase the risk of frailty. Methods: We searched PubMed, Web of Science, The Cochrane Library, EMBASE from inception to March 2022. Quality assessment was conducted using the NOS. Data was analysed in a pooled a random-effects meta-analysis. Our primary outcome was the impact of frailty on mortality in adults with Chronic Obstructive Pulmonary Disease (COPD) diagnosis according to the guidelines. Secondary outcomes were: frailty and association with readmissions, hospitalisations, exacerbation rates, and prevalence of frailty in COPD. Results: We identified 25 studies, with 5882 participants. The median prevalence of frailty was 47 (IQR, 39.3-66.3, range 6.4-72%). There was an association between COPD patients living with frailty and increased risk of mortality versus COPD patients without frailty (pooled OR,4.21 (95% CI 2.99-5.93, I2 55%). A descriptive analysis of relationship between frailty and hospital readmission and all cause hospitalization showed positive associations. The relationship between frailty and the risk of exacerbation showed a pooled OR, 1.45 (95% CI 0.37-5.70, I2 80%). Conclusion: Frailty is significantly associated with higher mortality risk in COPD. Frailty is common in patients with COPD and its measurement should be considered in clinical practice to better characterise COPD.

2023 - Frailty prevalence and association with clinical outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease. [Articolo su rivista]
Verduri, Alessia; Carter, Ben; Rice, Ceara; Laraman, Ames; Barton, Eleanor; Clini, Enrico; Maskell, Nick; Hewitt, Jonathan
abstract

Background: Frailty is a syndrome characterised by increase vulnerability to negative outcomes. Interstitial Lung Disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. Methods: We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, Systemic sclerosis-associated ILD, Connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough data allowed a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. Results: We identified 6 relevant studies incorporating 1471 ILD patients (age 68.3±SD2.38; 50% male), which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR=1.97(1.32-3.06) within 6 months in frail ILD patients. We identified 3 studies on frailty in asthma and no studies in pleural disease. The median prevalence in asthma was 9.5% (IQR7.8-11.3). Conclusions: Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population. The review found three studies relating to frailty in asthma, which did not examine its impact on outcomes. No studies relating to pleural disease and frailty were identified.

2023 - Molecular biology and therapeutic targets of primitive tracheal tumors: focus on tumors derived by salivary glands and squamous cell carcinoma. [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Samarelli, ANNA VALERIA; Cappiello, Gaia; Andreani, Alessandro; Tabbì, Luca; Livrieri, Francesco; Bosi, Annamaria; Nori, Ottavia; Mattioli, Francesco; Bruzzi, Giulia; Marchioni, Daniele; Clini, Enrico
abstract

2023 - One-year clinical experience on the use of Nintedanib in Systemic Sclerosis [Articolo su rivista]
Magnani, Luca; Spinella, Amelia; Testoni, Sofia; Lumetti, Federica; Scelfo, Chiara; Dardani, Lucia; Bajocchi, Gianluigi; Clini, Enrico; Salvarani, Carlo; Giuggioli, Dilia
abstract

AIM- Systemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is one of the most common causes of death. In 2019 Nintedanib was approved for SSc-related ILD, due to randomized clinical trials (RCTs) demonstrating a reduction in the annual rate of decline in Forced Vital Capacity (FVC). METHODS We reviewed eleven patients with SSc-related ILD from January 2020 to January 2021 and who started Nintedanib 150 mg twice a day. RESULTS- Non-Specific Interstitial Pneumonia (NSIP) was the most frequent HRCT pattern, followed by Usual Interstitial Pneumonia (UIP) and UIP/NSIP pattern. The mean of Modified Rodnan Skin Score (mRSS) at baseline was 9.23 (±10SD) points without any significant improvement during the follow-up. Patients continued their ongoing therapy for lung involvement. Mean FVC was 2233.6 ml [+/- 1066 ml] (61.3% predicted) at beginning and remained stable during the follow-up period. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 at baseline to 2.5 at the end of follow up and the mean of the Borg scale of dyspnea ameliorated from 7.27 at baseline to 6 at twelve months. Both the differences were not significant. Two patients stop therapy: one for partial intestinal obstruction and one for incoercible diarrhea. CONCLUSION- Nintedanib was generally well tolerated and we did not record any serious adverse event

2023 - Physiological effects of lung protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study. [Articolo su rivista]
Tonelli, Roberto; Grasso, Salvatore; Cortegiani, Andrea; Ball, Lorenzo; Castaniere, Ivana; Tabbì, Luca; Fantini, Riccardo; Andrisani, Dario; Gozzi, Filippo; Moretti, Antonio; Bruzzi, Giulia; Manicardi, Linda; Cerri, Stefania; Samarelli, ANNA VALERIA; Raineri, Giulia; Murgolo, Francesco; Carzoli, Andrea; Di Mussi, Rossella; Busani, Stefano; Rizzoni, Raffaella; Grasselli, Giacomo; Clini, Enrico; Marchioni, Alessandro
abstract

Background- Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. Methods- Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero=ZEEP, 4-8 cmH2O=PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure-PL,EE=PEEPTITRATED) were used for measurements. Results- Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [-7.6 – -2.3] cmH2O and lung elastance (EL) 44 [40 – 51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p=0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3 – 1.5] cmH2O and EL to 49 [43 – 59] (p=0.004 and p<0.001 compared to ZEEP and PEEPLOW, respectively). PL decreased at PEEPLOW (p=0.018) and increased at PEEPTITRATED (p=0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and PL. Conclusions- In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

2023 - Prevalence of asthma and COPD in a cohort of patients at the follow up after COVID-19 pneumonia. [Articolo su rivista]
Verduri, Alessia; Hewitt, Jonathan; Carter, Ben; Tonelli, Roberto; Clini, Enrico; Beghè, Bianca
abstract

Not available

2023 - Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes. [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Barbieri, Sara; Marchio', Tommaso; Caselgrandi, Agnese; Motta, Federico; Beghe', Bianca; Verduri, Alessia; Belli, Michela; Gozzi, Licia; Iadisernia, Vittorio; Faltoni, Matteo; Burastero, Giulia; Dessilani, Andrea; DEL MONTE, Martina; Dolci, Giovanni; Bacca, Erica; Franceschi, Giacomo; Yaacoub, Dina; Volpi, Sara; Mazzochi, Alice; Clini, Enrico; Mussini, Cristina
abstract

Background- The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods- This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: “fit/resilient”, “fit/non-resilient”, “frail/resilient” and “frail/non-resilient”. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results- 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score <61.60 were the phenotypes “frail/non-resilient” (OR=4.69, CI:2.08-10.55), “fit/non-resilient” (OR=2.79, CI:1.00-7.73). Predictors for EQ-5D-5L <89.7% were the phenotypes “frail/non-resilient” (OR=5.93, CI: 2.64-13.33) and “frail/resilient” (OR=5.66, CI:1.93-16.54). Predictors of impaired IC (below the mean score value) were “frail/non-resilient” (OR=7.39, CI:3.20-17.07), and “fit/non-resilient” (OR=4.34, CI:2.16-8.71) phenotypes. Conclusions- Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS.

2023 - Role of selective digestive decontamination in the prevention of VAP in COVID-19 patients: a pre-post observational study. [Articolo su rivista]
Biagioni, Emanuela; Ferrari, Elena; Gatto, Ilenia; Serio, Lucia; Farinelli, Carlotta; Coloretti, Irene; Talamonti, Marta; Tosi, Martina; Meschiari, Marianna; Tonelli, Roberto; Venturelli, Claudia; Mussini, Cristina; Clini, Enrico; Sarti, Mario; Cossarizza, Andrea; Busani, Stefano; Girardis, Massimo.
abstract

The aim of our study was to evaluate whether the introduction of SDD in a structured protocol for VAP prevention was effective in reducing the occurrence of ventilator associated pneumonia (VAP) in COVID19 patients without changes in the microbiological pattern of antibiotic resistances. This observational pre-post study including adult patients requiring invasive mechanical ventilation (IMV) for severe respiratory failure related to SARS-CoV-2 admitted in three COVID19 intensive care units (ICUs) in an Italian hospital from February 22, 2020, to March 8, 2022. Selective digestive decontamination (SDD) was introduced from the end of April 2021 in the structured protocol for VAP prevention. The SDD consisted of a tobramycin sulphate, colistin sulphate and amphotericin B suspension applied in the patient oropharynx and the stomach via nasogastric tube. Three-hundred forty-eight patients were included in the study. In the 86 patients (32,9%) who received SDD the occurrence of VAP decreased by 7,7% (p = 0,192) compared to patients who did not receive SDD. Onset time of VAP, the occurrence of multidrug-resistant microorganisms AP, the length of invasive mechanical ventilation and hospital mortality were similar in patients who received and who did not receive SDD. The multivariate analysis adjusted for confounders showed that the use of SDD reduces the occurrence of VAP (HR 0,536, CI 0,338-0,851; p = 0,017) Our pre-post observational study indicates that the use of SDD in a structured protocol for VAP prevention seems to reduce the occurrence of VAP without changes in the incidence of multidrug-resistant bacteria in COVID19 patients.

2023 - The association of procalcitonin and C- reactive protein with bacterial infections acquired during ICU stay in COVID-19 critically ill patients. [Articolo su rivista]
Campani, Simone; Talamonti, Marta; Dall’Ara, Lorenzo; Coloretti, Irene; Gatto, Ilenia; Biagioni, Emanuela; Tosi, Martina; Meschiari, Marianna; Tonelli, Roberto; Clini, Enrico; Cossarizza, Andrea; Guaraldi, Giovanni; Mussini, Cristina; Sarti, Mario; Trenti, Tommaso; Girardis, Massimo
abstract

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identify-ing bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19. This observa-tional study included adult patients admitted to three COVID-19 intensive care units (ICU) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay≥ 11 days. The values of PCT and CRP collected on the day of infection diagnosis were com-pared to those collected on day 11 after ICU admission, the median time for infection occurrence, in patients without secondary infection. The receiver operating characteristic curve (ROC) and multivariate logistic model were used to assess PCT and CRP association with secondary infec-tions. Two hundred and seventy-nine patients were included, of whom 169 (60,6%) developed secondary infection after ICU admission. The PCT and CRP values observed on the day of the in-fection diagnosis were larger (p< 0,001) than those observed on day 11 after ICU admission in pa-tients without secondary infections. The ROC analysis calculated an AUC of 0,744 (95%CI 0,685-0,803) and 0,754 (95%CI 0,695-0,812) for PCT and CRP, respectively. Multivariate logistic models showed that PCT ≥ 0,16 ng/ml and CRP≥ 1,35 mg/dl were associated (p<0,001) with infections acquired during ICU stay. Our results indicated that PCT and CRP values were associated with developing secondary infections in COVID-19 patients with an ICU stay > 11 days with an ac-ceptable level of diagnostic accuracy using cut-off values lower than those commonly used in no-COVID-19 patients.

2022 - Association between respiratory distress time and invasive mechanical ventilation in COVID-19 patients: a multicentre regional cohort study. [Articolo su rivista]
Busani, Stefano; Coloretti, Irene; Baciarello, Marco; Bellini, Valentina; Sarti, Marco; Biagioni, Emanuela; Tonelli, Roberto; Marchioni, Alessandro; Clini, Enrico; Guaraldi, Giovanni; Mussini, Cristina; Meschiari, Marianna; Tonetti, Tommaso; Pisani, Lara; Nava, Stefano; Bignami, Elena; Ranieri, Marco; Girardis, Massimo
abstract

Aim: to determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. Materials and methods: an observational multicentre cohort study of patients hospitalised in five COVID-19–designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO₂/FiO₂ ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. Measurements and main results: we analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p<0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48–12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89–39.41], p <0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. Discussion: albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients’ need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

2022 - Biological effects of COVID-19 on lung cancer: can we drive our decisions? [Articolo su rivista]
Aramini, Beatrice; Masciale, Valentina; Samarelli, Anna V.; Tonelli, Roberto; Cerri, Stefania; Clini, Enrico; Stella, Franco; Dominici, Massimo
abstract

COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of pro-inflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19.

2022 - Broncopneumopatia cronica ostruttiva (BPCO) - cap.3 [Articolo su rivista]
Cirio, Serena; Clini, Enrico M.; Gaudiello, Giuseppe; Gigliotti, Francesco; Vitacca., Michele
abstract

La broncopneumopatia cronica ostruttiva (BPCO) La BPCO è una patologia respiratoria croni- ca progressiva e un problema sanitario di rilevanza pubblica ed economica in tutto il mondo. I programmi di riabilitazione polmonare (RP) sono interventi sicuri, in grado di migliorare la capacità d’esercizio, i sintomi e la qualità di vita. La RP gode di un ottimo rapporto costo- ef cacia, è indicata in tutti gli stadi di malattia ed è in grado di limitare l’evoluzione della fragilità, ridurre il numero di accessi ospedalieri e determinare un aumento della sopravvi- venza. I programmi di RP devono quindi essere necessariamente inclusi nei pacchetti di cure integrate dei pazienti con BPCO.

2022 - Comparison between first and second wave of COVID-19 outbreak in older people: the COPE multicentre European observational cohort study [Articolo su rivista]
Verduri, A.; Short, R.; Carter, B.; Braude, P.; Vilches-Moraga, A.; Quinn, T. J.; Collins, J.; Lumsden, J.; Mccarthy, K.; Evans, L.; Myint, P. K.; Hewitt, J.; Clini, E.; Rickard, F.; Hesford, J.; Mitchell, E.; Hartrop, K.; Murphy, C.; Aggrey, K.; Bilan, J.; Quinn, T.; Kelly, J.; Murphy, C.; Moug, S.; Barlow-Pay, F. -.; Khan, A.; Espinoza, M. F. R.; Kneen, T.; Allafi, H.; Dafnis, A.; Vidal, M. N.; Price, A.; Pearce, L.; Einarsson, A.; Mccrorie, E. B.
abstract

Background: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise healthcare systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and Wave 2 (W2). Methods: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from 13 hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. Results: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median (interquartile range), W2 = 79 (73-84); W1 = 80 (74-86); had a greater proportion of men (59.4% vs. 53.0%); had lower 28-day mortality (29.1% vs. 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality adjusted hazard ratio (aHR) = 0.78 [95% confidence interval (CI) 0.65-0.93], 28-day mortality adjusted odds ratio = 0.80 (95% CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95% CI 0.59-0.81). Patients in W2 were less frail, CFS [adjusted mean difference (aMD) = -0.50, 95% CI -0.81, -0.18], as well as presented with lower C-reactive protein (aMD = -22.52, 95% CI -32.00, -13.04). Conclusions: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline.

2022 - Correction: Endobronchial valve positioning for alveolar-pleural fistula following ICU management complicating COVID-19 pneumonia (BMC Pulmonary Medicine, (2021), 21, 1, (307), 10.1186/s12890-021-01653-w) [Articolo su rivista]
Donatelli, P.; Trentacosti, F.; Pellegrino, M. R.; Tonelli, R.; Bruzzi, G.; Andreani, A.; Cappiello, G. F.; Andrisani, D.; Gozzi, F.; Mussini, C.; Busani, S.; Cavaliere, G. V.; Girardis, M.; Bertellini, E.; Clini, E.; Marchioni, A.
abstract

2022 - Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality. [Articolo su rivista]
Gatto, Ilenia; Biagioni, Emanuela; Coloretti, Irene; Farinelli, Carlotta; Avoni, Camilla; Caciagli, Valeria; Busani, Stefano; Sarti, Mario; Pecorari, Monica; Gennari, William; Guaraldi, Giovanni; Franceschini, Erica; Meschiari, Marianna; Mussini, Cristina; Tonelli, Roberto; Clini, Enrico; Cossarizza, Andrea; Girardis, Massimo; Gibellini, Lara
abstract

Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of COVID-19 patients admitted to the intensive care unit (ICU). Methods: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. Results: CMV blood reactivation was observed in 88 patients (20,4%) of the 431 patients studied. SAPS II score (HR 1,031, 95% CI 1,010-1,053, p=0,006), platelet count (HR 0,0996, 95% CI 0,993-0,999, p=0,004), invasive mechanical ventilation (HR 2,611, 95% CI 1,223-5,571, p=0,013) and secondary bacterial infection (HR 5,041; 95% CI 2,852-8,911, p<0,0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67,0%) than in patients without (24,5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1,141, 95% CI 0,757-1,721, p=0,528). Conclusion: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

2022 - Delirium and risk factors in patients undergoing non-invasive ventilation for de novo acute respiratory failure: an observational multicenter trial. [Articolo su rivista]
Tabbì, Luca; Tonelli, Roberto; Comellini, Vittoria; Dongilli, Roberto; Sorgentone, Sara; Spacone, Antonella; Cristina Paonessa, Maria; Sacchi, Marianna; Falsini, Laura; Boni, Elisa; Ribuffo, Viviana; Bruzzi, Giulia; Castaniere, Ivana; Fantini, Riccardo; Marchioni, Alessandro; Pisani, Lara; Nava, Stefano; Clini, Enrico
abstract

Background- Noninvasive ventilation (NIV) still has high failure rate when used for de novo acute respiratory failure (ARF). Delirium may impact the outcome, however data regarding its incidence, timing of occurrence and clinical predictors in this subset of patients are scarce. Methods- Consecutive patients with de novo ARF subjected to NIV were recruited in 10 Italian Respiratory Intensive Care Units (RICUs) and Intensive Care Units (ICUs). Demographics and clinical features, including tolerance to interface and NIV setting were recorded on admission and during stay, whereas delirium onset and type was assessed by the (Confusion Assessment Method for ICU (CAM-ICU)-7 scale and Richmond Agitation Sedation Scale (RASS) twice/per day up to a week. The association between clinical variables and the occurrence of delirium and its influence on NIV failure and other clinical outcomes were analyzed. Results- Thirty-two out of 90 enrolled patients (36%) developed delirium over 7 days upon admission; median time to onset was 48 hours (24–60). Older age (OR=2.7 [1.9–9], p=0.01), the presence of cancer OR=3.7 [2–5.4], p=0.002), sepsis (OR=1.7 [1.1–3.4], p=0.01), SOFA score (OR=1.8 [1.1–3.1], p=0.01), low tolerance to interface (OR=3.2 [2.1–5], p=0.002), use of helmet (OR=1.9 [1.2–4.3] p=0.04), and higher pre-DELIRIC (OR=3.5 [1.3–15], p=0.03) and BORG (OR=1.7 [1.1–4.6], p=0.02] scores were significantly associated with delirium. Delirium had high risk for NIV failure (HR = 3.5 95%CI [1.4–8.6], p=0.0002) and it significantly associated with longer RICU/ICU stay and higher mortality. Conclusion- Delirium onset in acute hypoxic patients undergoing NIV is frequent and negatively affects the outcome. Multiple related clinical factors should be addressed early on admission to prevent the delirium-related risk of NIV failure in these patients.

2022 - Different Methods to Improve the Monitoring of Noninvasive Respiratory Support of Patients with Severe Pneumonia / ARDS Due to COVID-19: An Update. [Articolo su rivista]
Pelosi, Paolo; Tonelli, Roberto; Torregiani, Chiara; Baratella, Elisa; Confalonieri, Marco; Battaglini, Denise; Marchioni, Alessandro; Confalonieri, Paola; Clini, Enrico; Salton, Francesco; Ruaro, Barbara
abstract

The last guidelines for the hospital care of patients affected by coronavirus disease-2019 (COVID-19)-related acute respiratory failure have moved towards a widely accepted use of noninvasive respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinicalradiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruit ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (Ppl) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, despite further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for a clinical-physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

2022 - Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: A retrospective multicenter cohort study [Articolo su rivista]
Tonelli, R; Pisani, L; Tabbì, L; Comellini, V; Prediletto, I; Fantini, R; Marchioni, A; Andrisani, D; Gozzi, F; Bruzzi, G; Manicardi, L; Busani, S; Mussini, C; Castaniere, I; Bassi, I; Carpano, M; Tagariello, F; Corsi, G; D' amico, R; Girardis, M; Nava, S; Clini, E.
abstract

Introduction- In non-intubated patients with COVID-19 pneumonia, awake prone position associated with non-invasive respiratory support (NRS) demonstrated only physiological benefits. Nonetheless, it might be arguable that at least a selected subset of these patients is going to obtain significant clinical gains. Methods- This retrospective cohort study was conducted in two teaching hospitals comparing effects of awake prone position in addition to usual care (PP) with standard care alone (SC)in severe and critical COVID-19 patients undergoing NRS. Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated with ETI were also investigated in PP group. Results- A cohort of 114 patients (38 and 76 in PP and SC group, respectively) was analyzed. Greater ETI risk reduction rate was observed in PP as compared with SC both at unadjusted estimates (HR=0.45 95%CI [0.2-0.9], p=0.02), and even after adjustment for confounders (HR=0.59 95%CI[0.3-0.94], p=0.03). Compared with SC, PP group also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay, but not in mortality or tracheostomy rate. Conclusion- Early awake proning in spontaneously breathing Covid-19 patients is associated with a risk reduction of intubation rate.Findings prompt further randomized controlled trials to answer the pending questions on the real efficacy of PP in this setting.

2022 - Endoscopic Bronchopleural Fistula Repair Using Autologous Fat Graft [Articolo su rivista]
Marchioni, Alessandro; Mattioli, Francesco; Tonelli, Roberto; Andreani, Alessandro; Cappiello, Gaia Francesca; Serafini, Edoardo; Stefani, Alessandro; Marchioni, Daniele; Clini, Enrico
abstract

Bronchopleural fistula (BPF) represents a not rare catastrophic complication of pulmonary resection with high mortality rates. While surgical treatments of BPF are often technically difficult and can only be tolerated by a limited number of patients, less invasive endoscopic approaches showed variable success rates, mainly related to the size of the fistula. With this report, we describe for the first time the successful treatment of large BPF by means of endoscopic autologous fat implantation and we discuss the surgical technical details of the procedure.

2022 - Extensive tracheal injuries: a reasoned multi-step approach to guarantee mechanical ventilatory support developed during COVID-19 pandemic. [Articolo su rivista]
Mattioli, F; Martone, A; Andreani, A; Cappiello, G; Tonelli, R; Clini, E; Marchioni, A.
abstract

COVID-19 pandemic has notably increased the need for prolonged mechanical ventilation (MV) in patients with respiratory failure. This has increased the risk of extensive tracheal injuries (ETI) associated with life-threatening complications in very complex patients. Furthermore, tracheal injury treatment in COVID-19 patients has not been described yet. Three COVID-19 patients with ETI who required MV treated between April and November 2020 were included. A multi-step approach was performed in order to restore tracheal integrity with a custom remodeled stent and tracheostomy tube placement to allow ventilatory support. Efficient MV with no residual air leaks was obtained in all cases. One patient died six weeks after the procedure due to COVID-19 lung damage. Two patients have completely been weaned from MV. This multi-step procedure could be used in order to maintain ventilatory support in case of ETI, working as a bridge to subsequent surgery when clinical conditions improve.

2022 - First and second wave among hospitalized COVID-19 patients with severe pneumonia: a comparison of 28-day mortality over 1-year pandemic in a tertiary university hospital in Italy. [Articolo su rivista]
Meschiari, M; Cozzi-Lepri, A; Tonelli, R; Bacca, E; Menozzi, M; Franceschini, E; Cuomo, G; Bedini, A; Volpi, S; Milic, J; Brugioni, L; Romagnoli, E; Pietrangelo, A; Corradini, E; Coloretti, I; Biagioni, E; Busani, S; Girardis, M; Cossarizza, A; Clini, E; Guaraldi, G; Mussini, C.
abstract

Objectives: The first COVID-19-19 epidemic wave was over the period February-May 2020. Since October 1st, 2020 Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. Design: Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of hazard ratios (HRs) with 95% confidence intervals (CI). A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. Setting: University Hospital of Modena, Italy. Patients admitted to hospital for severe COVID-19 pneumonia during the first (February 22nd – May 31st, 2020) and second wave (October 1st- December 31st, 2020) were included. Results: During the two study periods, a total of 1,472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1,023 during the second. Median age was 70 years (IQR:56-80), 37% females, 49% with PaO /FiO < 250 mmHg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI:16.3-23.7) during the first wave vs. 14.2% (95% CI:12.0-16.3) in the second (log-rank test p-value= 0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the 2nd wave (aHR=0.64, 95% CI: 0.45, 0.90, p- value=0.01). Conclusions: In our hospitalized COVID-19 patients with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared to the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.

2022 - High flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxemia: a randomized controlled trial. [Articolo su rivista]
Crimi, Claudia; Noto, Alberto; Madotto, Fabiana; Ippolito, Mariachiara; Nolasco, Santi; Campisi, Raffaele; De Vuono, Stefano; Fiorentino, Giuseppe; Pantazopoulos, Ioannis; Chalkias, Athanasios; Libra, Alessandro; Mattei, Alessio; Scala, Raffaele; Clini, Enrico; Ergan, Begum; Lujan, Manel; Carlos Winck, João; Giarratano, Antonino; Carlucci, Annalisa; Gregoretti, Cesare; Groff, Paolo; Cortegiani., Andrea
abstract

Rationale- In COVID-19 patients with mild hypoxemia, the clinical benefit of high flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population. Methods- In this multicentre, randomised, parallel-group, open-label trial, COVID-19 patients with peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (i.e., continuous positive airway pressure, noninvasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with FiO2 ≤30% or PaO2/FiO2 ratio >300 mmHg). Results- Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference -8.2% [95%CI -18 +1.4]; RR 0.79 [95%CI, 0.59-1.05]; p= 0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2 [95%CI -1.5% to +18.0%], RR 1.14 [95%CI 0.98 to 1.32]), ICU admission (7.7% vs 11.0%, mean difference -0.2 days [95%CI -1.2 to +0.7], absolute risk difference -3.3% [95%CI -9.3% to +2.6]), in hospital length of stay (11 [IQR 8-17] vs 11 [IQR 7-20] days, absolute risk difference -1.0% [95%CI -3.0% to +1.0]). Conclusions- Among patients with COVID-19 pneumonia and mild hypoxemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support.

2022 - Inspiratory effort and respiratory mechanics in spontaneously breathing patients with acute exacerbation of idiopathic pulmonary fibrosis: a retrospective matched control study. [Articolo su rivista]
Tonelli, Roberto; Castaniere, Ivana; Cortegiani, Andrea; Tabbì, Luca; Fantini, Riccardo; Andrisani, Dario; Gozzi, Filippo; Moretti, Antonio; Bruzzi, Giulia; Manicardi, Linda; Cerbone, Caterina; Nani, Chiara; Biagioni, Emanuela; Cerri, Stefania; Samarelli, Valeria; Busani, Stefano; Girardis, Massimo; Marchioni, Alessandro; Clini, Enrico
abstract

Background- Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. Methods- Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive noninvasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔP es ) and respiratory mechanics before and 2 hours after NIV start were collected as primary outcome. Correlation between positive end-expiratory pressure (PEEP) levels and changes of dynamic compliance (dynC RS ) and PaO 2 /FiO 2 ratio was assessed. Further, an exploratory comparison with a historic cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO 2 /FiO 2 level was performed. Results- At baseline, AE-IPF presented high respiratory drive activation with ΔPes = 27 (21–34) cmH2O, respiratory rate (RR) = 34 (30–39) bpm and minute ventilation (VE) = 21 (20–26) L/min. Two hours after NIV application, ΔPes, RR and VE showed a significant reduction (16 [14–24] cmH2O, p<0.0001, 27 [25–30] bpm, p=0.001, and 18 [17–20] L/min, p=0.003, respectively) while no significant change was found for dynamic transpulmonary pressure (27 [21–34] VS 27 [25–36] cmH2O, p=0.2) expiratory tidal volume (Vte) (9.1 [8.7–10.1] VS 9.3 [8.7 – 9.9] mL/kg of predicted boy weight, p=0.2), dynCRS (28 [19–31] VS 26 [18–28] mL/cmH2O, p=0.1) and dynamic mechanical power (71 [49–94] VS 60 [51–74] J/min, p=0.1). PEEP levels negatively correlated with PaO 2 /FiO 2 ratio and dynC RS (r=–0.67, p=0.03 and r=–0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔP es , RR, VE and dynamic mechanical power. At difference with AE-IPF, Vte and dynC RS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO 2 /FiO 2 ratio and dynC RS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). Conclusions- In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS of similar severity.

2022 - La riabilitazione respiratoria e la prevenzione delle cadute nel paziente BPCO. [Articolo su rivista]
Mocellin, Anna; Campanini, Isabella; Merlo, Andrea; Clini, Enrico; Lusuardi., Mirco
abstract

L’alterazione dell’equilibrio, la disfunzione della muscolatura distale, la modificazione del controllo del moto e dei tempi di reazione sono solo alcune delle problematiche correlate alla broncopneumopatia cronica ostruttiva (BPCO) che aumentano il rischio di cadute nei pazienti affetti da tale patologia. L’importanza di questa sfera delle comorbilità e comorbilità del paziente respiratorio ha ricadute non solo personali e socioassistenziali, ma anche economiche a causa della portata della diffusione di tali patologie a livello mondiale e delle conseguenze sui sistemi sanitari nazionali che da esse scaturiscono. Oltre alle strategie farmacologiche la riabilitazione respiratoria risulta essere un intervento multidisciplinare in grado di offrire un programma di miglioramento fisico e psicologico dei pazienti BPCO e in quelli affetti da patologie respiratorie croniche in generale. Rimangono, tuttavia, alcuni punti aperti, sia per quanto riguarda le nuove proposte e le differenti tipologie di programmi disponibili, sia in merito allo studio e alla quantificazione dell’impatto che la riabilitazione respiratoria ha su aspetti come la mortalità, l’equilibrio e il rischio di caduta nei pazienti affetti da BPCO.

2022 - Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome. [Articolo su rivista]
Milic, J; Barbieri, S; Gozzi, L; Brigo, A; Beghe', B; Verduri, A; Bacca, E; Iadisernia, V; Cuomo, G; Dolci, G; Yaacoub, D; Aprile, E; Belli, M; Venuta, M; Meschiari, M; Sebastiani, G; Clini, E; Mussini, C; Lonardo, A; Guaraldi, G; Raggi, P.
abstract

Background: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

2022 - Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Andreani, Alessandro; Cappiello, Gaia Francesca; Fermi, Matteo; Trentacosti, Fabiana; Castaniere, Ivana; Fantini, Riccardo; Tabbì, Luca; Andrisani, Dario; Gozzi, Filippo; Bruzzi, Giulia; Manicardi, Linda; Moretti, Antonio; Baroncini, Serena; Samarelli, ANNA VALERIA; Marchioni, Daniele; Pinelli, Massimo; DE SANTIS, Giorgio; Stefani, Alessandro; Mattioli, Francesco; Clini, Enrico
abstract

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different etiology. Although iatrogenic etiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent etiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.

2022 - Nasal pressure swings as the measure of inspiratory effort in spontaneously breathing patients with de novo acute respiratory failure [Articolo su rivista]
Tonelli, Roberto; Cortegiani, Andrea; Marchioni, Alessandro; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Biagioni, Emanuela; Busani, Stefano; Nani, Chiara; Cerbone, Caterina; Vermi, Morgana; Gozzi, Filippo; Bruzzi, Giulia; Manicardi, Linda; Rosaria Pellegrino, Maria; Beghe', Bianca; Girardis, Massimo; Pelosi, Paolo; Gregoretti, Cesare; Ball, Lorenzo; Clini, Enrico
abstract

Background- Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔP es ) and nasal (ΔP nos ) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. Methods- From January 1 st , 2021 to September 1 st , 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of noninvasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 hours after starting NRS. Correlation between ΔP es and ΔP nos served as primary outcome. The effect of ΔP nos measurements on respiratory rate and ΔP es was also assessed. Results- ΔP es and ΔP nos were strongly correlated at admission (R 2 =0.88, p<0.001) and 24 hours apart (R 2 =0.94, p<0.001). The nasal plug insertion and the mouth closure required for ΔP nos measurement did not result in significant change of respiratory rate and ΔP es . The correlation between measures at 24 hours remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R 2 =0.79, p<0.001] or non-invasive ventilation [R 2 =0.95, p<0.001]). Conclusions- In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔP nos might warrant further investigation as a measure of inspiratory effort in patients with ARF.

2022 - Persistent asthma hospitalisations and deaths require a national asthma prevention plan [Articolo su rivista]
Beghè, Bianca; Fabbri, Leonardo; Clini, Enrico.
abstract

Not available

2022 - Prognostic value of estimated glomerular filtration rate in hospitalised older patients (over 65) with COVID-19: a multicentre, European, observational cohort study. [Articolo su rivista]
Carter, B; Ramsay, Ea; Short, R; Goodison, S; Lumsden, J; Khan, A; Braude, P; Vilches-Moraga, A; Quinn, Tj; Mccarthy, K; Hewitt, J; Myint, Pk; Verduri, A; Clini, E; Cope, Study
abstract

Background: The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. Methods: Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February-June 2020 and October 2020-March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. Results: One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73-86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45-59 [Stage 3a] aHR = 1.26 (95%CI 1.02-1.55); eGFR 30-44 [Stage 3b] aHR = 1.41 (95%CI 1.14-1.73); eGFR 1-29 [Stage 4&5] aHR = 1.42 (95%CI 1.13-1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88-1.58), Stage 3b aOR = 1.40 (95%CI 1.03-1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16-2.35). Conclusion: eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality.

2022 - Rehabilitation of Difficult-to-Wean, Tracheostomized Patients Admitted to specialized unit: Retrospective Analyses Over 10-years. [Articolo su rivista]
Costi, Stefania; Brogneri, Antonio; Bagni, Chiara; Pennacchi, Giulia; Beneventi, Claudio; Tabbì, Luca; Dell'Orso, Daniela; Fantini, Riccardo; Tonelli, Roberto; Maria Beghi, Gianfranco; Clini, Enrico
abstract

Introduction: Rehabilitation outcomes of difficult-to-wean tracheostomized patients have been reported in relatively small case studies and described for a limited time span. This study de-scribes the characteristics and clinical outcomes of a large cohort of tracheostomized patients admitted to a specialized weaning unit over 10 years. Methods: We retrospectively analyzed da-ta collected from January 2010 to December 2019 on difficult-to-wean tracheostomized patients who underwent comprehensive rehabilitation. Clinical characteristics collected at admission were the level of comorbidity (by the Cumulative Illness Rating Scale – CIRS) and the clinical se-verity (by the Simplified Acute Physiology Score – SAPS II). The proportions of patients weaned, decannulated, and able to walk, the change in autonomy level according to the Bristol Activities of Daily Living (BADL) Scale, and the setting of hospital discharge was assessed and compared in a consecutive 5-year time periods (2010-2014 and 2015-2019) subgroup analysis. Results: A to-tal of 180 patients were included in the analysis. Patients’ anthropometry and preadmission clin-ical management in acute care hospital were similar across years, but the categories of underlying diagnosis changed (p<0.001) (e.g. chronic obstructive pulmonary disease – COPD – decreased), while the level of comorbidities increased (p=0.003). Decannulation rate was 45.6%. CIRS and SAPS II at admission were both significant predictors of clinical outcomes. The proportion of pa-tients whose gain in BADL score increased ≥2 points decreased over time. Conclusions: This study confirms the importance of rehabilitation in the weaning units for the severely disabled subset of tracheostomized patients. Comorbidities and severity at admission are significantly as-sociated with rehabilitation outcomes at discharge.

2022 - Risk factors for pulmonary air leak and clinical prognosis in patients with COVID-19 related acute respiratory failure: a retrospective matched control study. [Articolo su rivista]
Tonelli, Roberto; Bruzzi, Giulia; Manicardi, Linda; Tabbì, Luca; Fantini, Riccardo; Castaniere, Ivana; Andrisani, Dario; Gozzi, Filippo; Rosaria Pellegrino, Maria; Trentacosti, Fabiana; Dall'Ara, Lorenzo; Busani, Stefano; Franceschini, Erica; Baroncini, Serena; Manco, Gianrocco; Meschiari, Marianna; Mussini, Cristina; Girardis, Massimo; Beghe', Bianca; Marchioni, Alessandro; Clini, Enrico
abstract

Background- The role of excessive inspiratory effort in promoting alveolar and pleural rupture resulting in air leak (AL) in patients with SARS-CoV-2 induced acute respiratory failure (ARF) while on spontaneous breathing is undetermined. Methods- Among all patients with COVID-19 related ARF admitted to a respiratory intensive care unit (RICU) and receiving non-invasive respiratory support, those developing an AL were and matched 1:1 (by means of PaO2/FiO2 ratio, age, body mass index-BMI and subsequent organ failure assessment [SOFA]) with a comparable population who did not (NAL group). Esophageal pressure (ΔPes) and dynamic transpulmonary pressure (ΔPL) swings were compared between groups. Risk factors affecting AL onset were evaluated. The composite outcome of ventilator-free-days (VFD) at day 28 (including ETI, mortality, tracheostomy) was compared between groups. Results- AL and NAL groups (n=28) showed similar ΔPes, whereas AL had higher ΔPL (20 [16‐21] and 17 [11‐20], p=0.01 respectively). Higher ΔPL (OR=1.5 95%CI[1‐1.8], p=0.01), positive end‐expiratory pressure (OR=2.4 95%CI[1.2‐5.9], p=0.04) and pressure support (OR=1.8 95%CI[1.1-3.5], p=0.03), D-dimer on admission (OR=2.1 95%CI[1.3-9.8], p=0.03), and features suggestive of consolidation on computed tomography scan (OR=3.8 95%CI[1.1-15], p= 0.04) were all significantly associated with AL. A lower VFD score resulted in a higher risk (HR=3.7 95%CI [1.2-11.3], p=0.01) in the AL group compared with NAL. RICU stay and 90-day mortality were also higher in the AL group compared with NAL. Conclusions- In spontaneously breathing patients with COVID‐19 related ARF, higher levels of ΔPL, blood D‐dimer, NIV delivery pressures and a consolidative lung pattern were associated with AL onset.

2022 - STenting veRsus balloOn dilatation in patients with tracheal BEnign stenosis – the STROBE trial. [Articolo su rivista]
Marchioni, A; Andrisani, D; Tonelli, R; Andreani, A; Cappiello, G; Ori, M; Gozzi, F; Bruzzi, G; Baroncini, S; Nani, C; Femino', R; Manicardi, L; Mattioli, F; Fermi, M; Fantini, R; Tabbi', L; Castaniere, I; Presutti, L; Clini, E.
abstract

Background- It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy.  The main objective of this study was to compare the efficacy of BA and ST to cure treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods- A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or re-stenosis in the long-term(2 years) following the endoscopic procedure. Results- Sixty-six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan-Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (HR=3.9 95%CI [1.5-9.8], p=0.01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p=0.01). Conclusions- Compared to balloon dilatation, tracheal stenting seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation.

2022 - The burden of mild asthma: Clinical burden and healthcare resource utilisation in the NOVELTY study [Articolo su rivista]
Golam, S. M.; Janson, C.; Beasley, R.; Fitzgerald, J. M.; Harrison, T.; Chipps, B.; Hughes, R.; Mullerova, H.; Olaguibel, J. M.; Rapsomaniki, E.; Reddel, H. K.; Sadatsafavi, M.; Benhabib, G.; Mandhane, P.; Ruiz, X. B.; Mcivor, A.; Olmo, R. D.; Pek, B.; Lisanti, R. E.; Petrella, R.; Marino, G.; Stollery, D.; Mattarucco, W.; Chen, M.; Nogueira, J.; Chen, Y.; Parody, M.; Gu, W.; Pascale, P.; Hui, K. M. C.; Rodriguez, P.; Li, M.; Silva, D.; Li, S.; Svetliza, G.; Ma, L.; Victorio, C. F.; Qin, G.; Rolon, R. W.; Song, W.; Yanez, A.; Tan, W.; Baines, S.; Tang, Y.; Bowler, S.; Wang, C.; Bremner, P.; Wang, T.; Bull, S.; Wen, F.; Carroll, P.; Wu, F.; Chaalan, M.; Xiang, P.; Farah, C.; Xiao, Z.; Hammerschlag, G.; Xiong, S.; Hancock, K.; Yang, J.; Harrington, Z.; Yang, J.; Katsoulotos, G.; Zhang, C.; Kim, J.; Zhang, M.; Langton, D.; Zhang, P.; Lee, D.; Zhang, W.; Peters, M.; Zheng, X.; Prassad, L.; Zhu, D.; Reddel, H.; Bolivar Grimaldos, F.; Sajkov, D.; Arboleda, A. C.; Santiago, F.; Bueno, C. M.; Simpson, F. G.; Molina de Salazar, D.; Tai, S.; Bendstrup, E.; Thomas, P.; Hilberg, O.; Wark, P.; Kjellerup, C.; Cancado, J. E. D.; Weinreich, U.; Cunha, T.; Bonniaud, P.; Lima, M.; Brun, O.; Cardoso, A. P.; Burgel, P. -R.; Rabahi, M.; Chouaid, C.; Anees, S.; Couturaud, F.; Bertley, J.; de Blic, J.; Bell, A.; Debieuvre, D.; Cheema, A.; Delsart, D.; Chouinard, G.; Demaegdt, A.; Csanadi, M.; Demoly, P.; Dhar, A.; Deschildre, A.; Dhillon, R.; Devouassoux, G.; Fitzgerald, J. M.; Egron, C.; Kanawaty, D.; Falchero, L.; Kelly, A.; Goupil, F.; Killorn, W.; Kessler, R.; Landry, D.; Le Roux, P.; Luton, R.; Mabire, P.; Mahay, G.; Ide, Y.; Martinez, S.; Inomata, M.; Melloni, B.; Inoue, H.; Moreau, L.; Inoue, K.; Raherison, C.; Inoue, S.; Riviere, E.; Kato, M.; Roux-Claude, P.; Kawasaki, M.; Soulier, M.; Kawayama, T.; Vignal, G.; Kita, T.; Yaici, A.; Kobayashi, K.; Aries, S. P.; Koto, H.; Bals, R.; Nishi, K.; Beck, E.; Saito, J.; Deimling, A.; Shimizu, Y.; Feimer, J.; Shirai, T.; Grimm-Sachs, V.; Sugihara, N.; Groth, G.; Takahashi, K. -I.; Herth, F.; Tashimo, H.; Hoheisel, G.; Tomii, K.; Kanniess, F.; Yamada, T.; Lienert, T.; Yanai, M.; Mronga, S.; Javier, R. C.; Reinhardt, J.; Dominguez Peregrina, A.; Schlenska, C.; Corzo, M. F.; Stolpe, C.; Montano Gonzalez, E.; Teber, I.; Ramirez-Venegas, A.; Timmermann, H.; Rendon, A.; Ulrich, T.; Boersma, W.; Velling, P.; Djamin, R. S.; Wehgartner-Winkler, S.; Eijsvogel, M.; Welling, J.; Franssen, F.; Winkelmann, E. -J.; Goosens, M.; Barbetta, C.; Graat-Verboom, L.; Braido, F.; Veen, J. I.; Cardaci, V.; Janssen, R.; Clini, E. M.; Kuppens, K.; Costantino, M. T.; van den Berge, M.; Cuttitta, G.; van de Ven, M.; di Gioacchino, M.; Brunstad, O. P.; Fois, A.; Einvik, G.; Foschino-Barbaro, M. P.; Hoines, K. J.; Gammeri, E.; Khusrawi, A.; Inchingolo, R.; Oien, T.; Lavorini, F.; Chang, Y. -S.; Molino, A.; Cho, Y. J.; Nucera, E.; Hwang, Y. I.; Papi, A.; Kim, W. J.; Patella, V.; Koh, Y. -I.; Pesci, A.; Lee, B. -J.; Ricciardolo, F.; Lee, K. -H.; Rogliani, P.; Lee, S. -P.; Sarzani, R.; Lee, Y. C.; Vancheri, C.; Lim, S. Y.; Vincenti, R.; Min, K. H.; Endo, T.; Oh, Y. -M.; Fujita, M.; Park, C. -S.; Hara, Y.; Park, H. -S.; Horiguchi, T.; Park, H. -W.; Hosoi, K.; Rhee, C. K.; Yoon, H. J.; Morice, A.; Yoon, H. -K.; Pandya, P.; Garcia-Navarro, A. A.; Patel, M.; Andujar, R.; Roy, K.; Anoro, L.; Sathyamurthy, R.; Garcia, M. B.; Thiagarajan, S.; Mozo, P. C.; Turner, A.; Campos, S.; Vestbo, J.; Maldonado, F. C.; Wedzicha, W.; Castilla Martinez, M.; Wilkinson, T.; Serrano, C. C.; Wilson, P.; Comeche Casanova, L.; Al-Asadi, L. A.; Corbacho, D.; Anholm, J.; Campo Matias, F. D.; Averill, F.; Echave-Sustaeta, J.; Bansal, S.; Corral, G. F.; Baptist, A.; Gamboa Setien, P.; Campbell, C.; Garcia Clemente, M.; Campos, M. A.; Nunez, I. G.; Robaina, J. G.; Crook, G.; Garcia Salmones, M.; Deleon, S.; Marin Trigo, J. M.; Eid, A.; Fernandez, M. N.; Epstein, E.; Palomo, S. N.; Fritz, S.; Olaguibel Rivera, J.; Harris, H.; de Llano, L. P.; Hewitt, M.; Pueyo Bas
abstract

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced ≥1 exacerbation in the previous 12 months, of whom 72.3% experienced ≥1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation ± 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score <20), increasing to 55.6% for those with ≥2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring ≥1 emergency department visit and 1.1% requiring ≥1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

2022 - The role of immune response in the pathogenesis of idiopathic pulmonary fibrosis: far beyond the Th1/Th2 imbalance. [Articolo su rivista]
Spagnolo, Paolo; Tonelli, Roberto; Samarelli, ANNA VALERIA; Castelli, Gioele; Cocconcelli, Elisabetta; Petrarulo, Simone; Cerri, Stefania; Bernardinello, Nicol; Clini, Enrico; Saetta, Marina; Balestro., Elisabetta
abstract

Introduction: . Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown origin characterized by progressive scarring of the lung leading to irreversible loss of function. Despite the availability of two drugs that are able to slow down disease progression, IPF remains a deadly disease. The pathogenesis of IPF is poorly understood, but a dysregulated wound healing response following recurrent alveolar epithelial injury is thought to be crucial. Areas covered. In the last few years, the role of the immune system in IPF pathobiology has been reconsidered; indeed, recent data suggest that a dysfunctional immune system may promote and unfavorable interplay with pro-fibrotic pathways thus acting as a cofactor in disease development and progression. In this article, we review and critically discuss the role of T cells in the pathogenesis and progression of IPF in the attempt to highlight ways in which further research in this area may enable the development of targeted immunomodulatory therapies for this dreadful disease. Expert opinion: A better understanding of T cells interactions has the potential to facilitate the development of immune modulators targeting multiple T cell-mediated pathways thus halting disease initiation and progression.

2022 - Urgent need of novel biomarkers of acute dyspnea. [Articolo su rivista]
Beghe', B; Clini, E; Fabbri, L.
abstract

Not available

2021 - Acute severe asthma: management and treatment. [Articolo su rivista]
Bosi, A; Tonelli, R; Castaniere, I; Clini, E; Beghe', B.
abstract

Patients with acute asthma attack usually access the emergency room with severe functional impairment, despite low perception of symptoms. In this scenario, early functional assessment is essential focusing on vital parameters and respiratory function, alongside perceived dyspnea. Impairment of ventilatory mechanics due to progressive dynamic pulmonary hyperinflation should be promptly treated with medical inhalation and/or intravenous therapy, reserving intensive treatment in case of non-response and/or worsening of the clinical conditions. Therapeutic planning at patient's discharge is no less important than treatment management during emergency room access as educating the patient about therapeutic adherence significantly impact long-term outcomes of asthma. With this review we aim at exploring current evidence on acute asthma attack management, focusing of pharmacological and ventilatory strategies of care and highlighting the importance of patient education once clinical stability allows discharge from the emergency department.

2021 - Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator. [Articolo su rivista]
Mussini, C; Cozzi-Lepri, A; Menozzi, M; Meschiari, M; Franceschini, E; Rogati, C; Cuomo, G; Bedini, A; Iadisernia, M; Volpi, S; Milic, J; Tonelli, R; Brugioni, L; Pietrangelo, A; Girardis, M; Cossarizza, A; Clini, E; Guaraldi, G.; De biasi, S; Gibellini, Lara
abstract

Objectives: Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. Methods: This was a retrospective, observational cohort study among patients with severe COVID- 19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint IMV or death (yes/no) by end of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Results: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from admission, 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank pvalue<0.0001) and this amounted to a difference in HR of 0.40 (0.26-0.63, p=0.0001). The AUC in Creactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex. Conclusions: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex.

2021 - COVIDGuide una app per il triage e l'autovalutazione della COVID-19. [Articolo su rivista]
Demurtas, J; Tonelli, R; Celotto, S; Veronese, N; Lagolio, E; Rossi, F; Clini, E; Righi, E; Meer, A.
abstract

Introduzione- La pandemia senza precedenti da COVID-19 ha mostrato le debolezze dei sistemi sanitari e aperto nuovi spazi ad e-health e telemedicina. La letteratura recente afferma che i chatbot, se progettati e implementati in modo efficace, potrebbero essere strumenti utili per condividere rapidamente informazioni, promuovere comportamenti sani e aiutare a ridurre il peso psicologico dell'isolamento.Lo scopo di questo progetto è sviluppare e testare un sistema di supporto decisionale computerizzato (SSDC) in web-app sicuro e affidabile e valutarne l’utilizzo, fruibilità e gli esiti decisionali in termini di output. Metodi- Un team multidisciplinare è stato reclutato per pianificare e progettare, sulla base del SSDC medico SMASS, gli scenari della web-app COVID-Guide, un sistema di self-triage per i pazienti con sospetta COVID-19. Sono stati analizzati i dati di output del periodo Maggio-Settembre 2020 provenienti dalla Germania. Risultati- Nel periodo preso in esame il totale delle consultazioni in Germania è stato di 96012. 3415 (3,56%) consultazioni indicavano la necessità di una valutazione immediata, tramite l'attivazione del servizio di emergenza (chiamare un'ambulanza) - 1942, pari al 2,02% - o consigliando al paziente di recarsi in ospedale – 1743, pari al 1,54%. Conclusioni- I dati di utilizzo sembrano mostrare una buona fruibilità e un numero consistente di consultazioni effettuate.

2021 - Changes in clinical characteristics and outcomes of patients admitted to inpatient cardiac rehabilitation [Articolo su rivista]
Costi, S; Tonelli, R; Brogneri, A; Florini, A; Tilocca, N; Vicentini, M; Baroncini, S; Cerulli, M; Clini, E.
abstract

Aims: Cardiac rehabilitation (CR) have proven to be effective and beneficial in middle-aged and older patients. However, solid data in large cohorts of elderly individuals are yet to be explored. This retrospective study investigated the general characteristics, outcomes, and the level of re-sponse of patients referred to CR over 13 consecutive years. Methods: We reviewed the medical records of patients admitted to Villa Pineta Rehabilitation Hospital for exercise-based CR from 2006 to 2018. Patients’ baseline characteristics and changes following CR in upper limb weight-lifting test (ULW), 30-second sit-to-stand test (30STS), and the 6-minute walking test (6MWT) with associated Borg-related dyspnea (D) and fatigue (F) were collected. We also calculated the number of individuals reaching the minimal clinically relevant change (MCRC) following CR for each outcome. Results: 1551 patients (70.2 ± 9.7 years, 66% men) with complete data set were in-cluded in the analysis. Coronary artery bypass graft and cardiac valve replacement surgery were the most frequent surgical procedures leading to CR referral (41.1% and 35.8%, respectively). The patients’ age (p = 0.03), number of total comorbidities (p < 0.0001), and post-surgical complica-tions (p = 0.02) significantly increased over time. In contrast, the average absolute changes in ULW, 30STS and 6MWT with associated D and F, and the proportion of patients reaching the re-spective MCRC, remained constant over the same period. Conclusion: Patients admitted to exer-cise-based CR were older and had more comorbidities and complications over time. Outcomes, however, were not influenced in terms of absolute change nor clinically meaningful response.

2021 - Combined approach to define the clinical impact and decision making in asthmatics. [Articolo su rivista]
Clini, E; Fabbri, Lm.
abstract

Not available

2021 - Comments on “Preventive home therapy for symptomatic patients affected by COVID-19 and followed by teleconsultations” by D’Amato et al. [Articolo su rivista]
Adiletta, G; Baglioni, S; Bettoncelli, G; Bracciale, P; Cazzola, M; Clini, E; Cutrera, R; D’Adduzio, F; de Blasio, F; Ferraro, F; Fumagalli, R; Lequaglie, C; Matera, Mg; Numis, F; Palange, P; Picciolo, S; Potena, A; Romano, F; Sabato, E; Sacchetta, A; Spatafora, M; Stefanelli, F; Zottola, C.
abstract

Not available

2021 - Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9) [Articolo su rivista]
Perrone, F.; Piccirillo, M. C.; Ascierto, P. A.; Salvarani, C.; Parrella, R.; Marata, A. M.; Popoli, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Ripamonti, D.; Binda, F.; Bonfanti, P.; Squillace, N.; Castelli, F.; Muiesan, M. L.; Lichtner, M.; Calzetti, C.; Salerno, N. D.; Atripaldi, L.; Cascella, M.; Costantini, M.; Dolci, G.; Facciolongo, N. C.; Fraganza, F.; Massari, M.; Montesarchio, V.; Mussini, C.; Negri, E. A.; Botti, G.; Cardone, C.; Gargiulo, P.; Gravina, A.; Schettino, C.; Arenare, L.; Chiodini, P.; Gallo, C.; Piccirillo, M. C.; Schettino, C.; Gravina, A.; Gargiulo, P.; Arenare, L.; Ascierto, P. A.; Vitale, M. G.; Trojaniello, C.; Palla, M.; Bianchi, A. A. M.; Botti, G.; De Feo, G.; Miscio, L.; Gallo, C.; Chiodiniy, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Froldi, M.; Menicanti, L.; Cuppone, M. T.; Gobbo, G.; Baldessari, C.; Valenti, V.; Castelvecchio, S.; Poli, F.; Giacomazzi, F.; Piccinni, R.; Annnunziata, M. L.; Biondi, A.; Bussolari, C.; Mazzoleni, M.; Giachi, A.; Filtz, A.; Manini, A.; Poletti, E.; Masserini, F.; Conforti, F.; Gaudiano, G.; Favero, V.; Moroni, A.; Viva, T.; Fancoli, F.; Ferrari, D.; Niro, D.; Resta, M.; Ballotta, A.; Poli, M. D.; Ranucci, M.; Ripamonti, D.; Binda, F.; Tebaldi, A.; Gritti, G.; Pasulo, L.; Gaglio, L.; Del Fabbro, R.; Alborghetti, L.; Giustinetti, G.; Columpsi, P.; Cazzaniga, M.; Capici, S.; Sala, L.; Di Sciacca, R.; Mosca, G.; Pirozzi, M. R.; Castelli, F.; Muiesan, M. L.; Franceschini, F.; Roccaro, A.; Salvetti, M.; Paini, A.; Corda, L.; Ricci, C.; Tomasoni, L.; Nasta, P.; Lorenzotti, S.; Odolini, S.; Foca, E.; Roldan, E. Q.; Metra, M.; Magrini, S.; Borghetti, P.; Latronico, N.; Piva, S.; Filippini, M.; Tomasi, G.; Zuccala, F.; Cattaneo, S.; Scolari, F.; Bossini, N.; Gaggiotti, M.; Properzi, M.; Lichtner, M.; Del Borgo, C.; Marocco, R.; Belvisi, V.; Tieghi, T.; De Masi, M.; Zuccala, P.; Fabietti, P.; Vetica, A.; Mercurio, V. S.; Carraro, A.; Fondaco, L.; Kertusha, B.; Curtolo, A.; Del Giudice, E.; Lubrano, R.; Zotti, M. G.; Puorto, A.; Ciuffreda, M.; Sarni, A.; Monteforte, G.; Romeo, D.; Viola, E.; Damiani, C.; Barone, A.; Mantovani, B.; Di Sanzo, D.; Gentili, V.; Carletti, M.; Aiuti, M.; Gallo, A.; Meliante, P. G.; Martellucci, S.; Riggio, O.; Cardinale, V.; Ridola, L.; Bragazzi, M. C.; Gioia, S.; Valenzi, E.; Graziosi, C.; Bina, N.; Fasolo, M.; Ricci, S.; Gioacchini, M. T.; Lucci, A.; Corso, L.; Tornese, D.; Nijhawan, P.; Equitani, F.; Cosentino, C.; Palladino, M.; Leonetti, F.; Leto, G.; Gnessi, C.; Campagna, G.; Cesareo, R.; Marrocco, F.; Straface, G.; Mecozzi, A.; Cerbo, L.; Isgro, V.; Parrocchia, S.; Visconti, G.; Casati, G.; Calzetti, C.; Ariani, A.; Donghi, L.; Salerno, N. D.; Tacconelli, E.; Bertoldi, M.; Cattaneo, P.; Lambertenghi, L.; Motta, L.; Omega, L.; Albano, G.; Parrella, R.; Fraganza, F.; Atripaldi, L.; Montesarchio, V.; Scarano, F.; De Rosa, A.; Buglione, A.; Lavoretano, S.; Gaglione, G.; De Marco, M.; Sangiovanni, V.; Fusco, F. M.; Viglietti, R.; Manzillo, E.; Rescigno, C.; Pisapia, R.; Plamieri, G.; Maraolo, A.; Calabria, G.; Catalano, M.; Fiorentino, G.; Annunziata, A.; Polistina, G.; Imitazione, P.; Mollica, M.; Esposito, V.; D'Abraccio, M.; Punzi, R.; Bianco, V.; Sbreglia, C.; Del Vecchio, R. F.; Bordonali, A.; Franco, A.; Massari, M.; Salsi, P.; Fontana, M.; Virzi, G.; Calderone, O.; Molteni, A.; Gennarini, S.; Gnudi, U.; Ricci, M. A.; Titolo, G.; Mensi, G.; Vuotto, P.; Gasperini, B.; Mancini, M.; Pasquini, Z.; Spanu, P.; Clementi, S.; Pierini, S.; Bokor, D.; Gori, D.; Ciofetti, M.; Caimi, M.; Bettazzi, L.; Allevi, E.; Furiani, S.; Capitanio, C.; Mastropasqua, B.; Fara, C.; Pulitano, G.; Matsuno, J. S.; Porta, F. D.; Dolfini, V.; Beyene, N. B.; Bezzi, M.; Novali, M.; Viale, P.; Tedeschi, S.; Pascale, R.; Bruno, R.; Di Filippo, A.; Sachs, M.; Oggionni, T.; Di Stefano, M.; Mengoli, C.; Facchini, C.; De Nardo, D.; Frausini, G.; Mucci, L.; Tedesco, S.; Girolimetti, R.; Manfredini, E.; Di Carlo, A. M.; Espinosa, E.; Dennetta, D.; Ticinesi, A.; Meschi, T.
abstract

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article.

2021 - Defining Modern Pulmonary Rehabilitation: An Official American Thoracic Society Workshop Report. [Articolo su rivista]
Holland, Ae; Cox, Ns; Houchen-Wolloff, L; Rochester, C; Garvey, C; Zuwallack, R; Nici, L; Limberg, T; Lareau, S; Yawn, B; Gawlicki, M; Troosters, T; Steiner, M; Casaburi, R; Clini, E; Goldstein, R; Singh, Sj.
abstract

Pulmonary rehabilitation is a highly effective treatment for people with chronic lung disease but remains underutilised across the world. Recent years have seen emergence of new program models that aim to improve access and uptake, including telerehabilitation and low-cost home-based models. This workshop was convened to achieve consensus on the essential components of pulmonary rehabilitation, and to identify requirements for successful implementation of emerging program models. A Delphi process involving experts from across the world identified 13 essential components of pulmonary rehabilitation that must be delivered in any program model, encompassing patient assessment, program content, method of delivery and quality assurance, as well as 27 desirable components. Only those models of pulmonary rehabilitation that have been tested in clinical trials are currently considered as ready for implementation. The characteristics of patients most likely to succeed in each program model are not yet known and research is needed in this area. Health professionals should use clinical judgement to determine those patients who are best served by a center-based, multidisciplinary rehabilitation program. A comprehensive patient assessment is critical to personalization of pulmonary rehabilitation and to effectively addressing individual patient goals. Robust quality assurance processes are important to ensure that any pulmonary rehabilitation service delivers optimal outcomes for patients and health services. Workforce capacity building and training should consider the skills necessary for emerging models, many of which are delivered remotely. The success of all pulmonary rehabilitation models will be judged on whether the essential components are delivered and the expected patient outcomes achieved, including improved exercise capacity, reduced dyspnea, enhanced health-related quality of life and reduced hospital admissions.

2021 - Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection [Articolo su rivista]
Mussini, C; Cozzi-Lepri, A; Menozzi, M; Meschiari, M; Franceschini, E; Milic, J; Brugioni, L; Pietrangelo, A; Girardis, M; Cossarizza, A; Tonelli, R; Clini, E; Massari, M; Bartoletti, M; Ferrari, A; Cattelan, Am; Zuccalà, P; Lichtner, M; Rossotti, R; Girardi, E; Nicastri, E; Puoti, M; Antinori, A; Viale, Pl; Guaraldi, G.
abstract

Background: The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients’ profile. Methods: Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. Results: 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. Conclusions: Our score could assist clinicians in identifying, early after tocilizumab, patients who are likely to progress to mechanical ventilation or death so that they could be selected for eventual rescue therapies.

2021 - Development of post-COVID-19 cardiovascular events: An analysis of clinical features and risk factors from a single hospital retrospective study [Articolo su rivista]
Cuomo, G.; Puzzolante, C.; Iadisernia, V.; Santoro, A.; Menozzi, M.; Carli, F.; Digaetano, M.; Orlando, G.; Franceschini, E.; Bedini, A.; Meschiari, M.; Manzini, L.; Corradi, L.; Milic, J.; Borghi, V.; Brugioni, L.; Pietrangelo, A.; Clini, E.; Girardis, M.; Guaraldi, G.; Mussini, C.
abstract

Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific inter-est. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student’s t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture.

2021 - Differences between acute exacerbations of idiopathic pulmonary fibrosis and other interstitial lung diseases. [Articolo su rivista]
Faverio, P; Stainer, A; Conti, S; Madotto, F; De Giacomi, F; Della Zoppa, M; Vancheri, V; Pellegrino, Mr; Tonelli, R; Cerri, S; Clini, E; Mantovani, L; Pesci, A; Luppi, F.
abstract

Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed “acute exacerbation” (AE). Incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian University hospitals from 2009 to 2016. Patients included in the analysis has been divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups, respectively 19% in non-IPF group and 43% in IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers with neutrophilia on differential blood cell count (HR 1.02 [CI 1.01 – 1.04]), presence of pulmonary hypertension (HR 1.85 – [CI 1.17 – 2.92]) and diagnosis of IPF (HR 2.31 [CI 1.55 – 3.46]) resulted negative prognostic factors in our analysis, while lymphocytosis on differential count seemed to act as a protective prognostic factor (OR 0.938 [CI 0.884 – 0.995]). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings.

2021 - Dissecting the role of mesenchymal stem cells in idiopathic pulmonary fibrosis: cause or solution? [Articolo su rivista]
Samarelli, Av; Tonelli, R; Heijink, I; Martin Medina, A; Marchioni, A; Bruzzi, G; Castaniere, I; Andrisani, D; Gozzi, F; Manicardi, L; Moretti, A; Cerri, S; Fantini, R; Tabbì, L; Nani, C; Mastrolia, I; Weiss, Dj; Dominici, M; Clini, E.
abstract

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonias, characterized by chronic and progressive fibrosis subverting the lung’s architecture, pulmonary functional decline, progressive respiratory failure, and high mortality (median survival 3 years after diagnosis). Among the mechanisms associated with disease onset and progression, it has been hypothesized that IPF lungs might be affected either by a regenerative deficit of the alveolar epithelium or by a dysregulation of repair mechanisms in response to alveolar and vascular damage. This latter might be related to the progressive dysfunction and exhaustion of the resident stem cells together with a process of cellular and tissue senescence. The role of endogenous mesenchymal stromal/stem cells (MSCs) resident in the lung in the homeostasis of these mechanisms is still a matter of debate. Although endogenous MSCs may play a critical role in lung repair, they are also involved in cellular senescence and tissue ageing processes with loss of lung regenerative potential. In addition, MSCs have immunomodulatory properties and can secrete anti-fibroticfactors. Thus, MSCs obtained from other sources administered systemically or directly into the lung have been investigated for lung epithelial repair and have been explored as a potential therapy for the treatment of lung diseases including IPF. Given these multiple potential roles of MSCs, this review aims both at elucidating the role of resident lung MSCs in IPF pathogenesis and the role of administered MSCs from other sources for potential IPF therapies.

2021 - ERS/EAACI statement on adherence to international adult asthma guidelines [Articolo su rivista]
Mathioudakis, Ag; Tsilochristou, O; Adcock, Ia; Bikov, A; Bjermer, L; Clini, E; Flood, B; Herth, F; Horvath, H; Kalayci, O; Papadopoulos, Ng; Ryan, D; Sanchez Garcia, S; Correia de Sousa, J; Tonia, T; Pinnock, H; Agache, I; Janson, C.
abstract

Clinical practice guidelines based on the best available evidence, aim to standardize and optimize asthma diagnosis and management. Nevertheless, there are concerns that particularly between different groups of healthcare professionals (HCPs), adherence to guidelines is suboptimal. Further to these concerns, the aims of this ERS/EAACI Statement were (1) via an international online survey, to evaluate and compare the understanding of and adherence to international asthma guidelines by HCPs of different specialties, (2) via systematic reviews of the literature, to assess effectiveness of strategies focused at improving implementation of guideline-recommended interventions, and compare process and clinical outcomes in patients managed by Specialists (respiratory physicians or allergists) or Generalists (internists or general practitioners). The online survey identified discrepancies between HCPs of different specialties which may be due to poor dissemination or lack of knowledge of the guidelines but also a reflection of the adaptations HCPs working in different clinical settings make, based on their resources. The systematic reviews demonstrated that multifaceted quality improvement initiatives addressing multiple challenges to guidelines adherence, or the input from additional specialized HCPs are most effective in improving guidelines adherence. More data are needed to evaluate differences in process and clinical outcomes among patients managed by Generalists or Specialists. Our results reveal a need for guidelines to consider the heterogeneity of real-life settings for asthma management and tailor their recommendations accordingly. Continuous, multifaceted quality improvement processes are required to optimize and maintain guidelines adherence. Validated referral pathways for uncontrolled asthma or for uncertain diagnosis are needed.

2021 - Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV2 infection: retrospective cohort study. [Articolo su rivista]
Coloretti, I; Busani, S; Biagioni, E; Venturelli, S; Munari, E; Marco, S; Dall’Ara, L; Tosi, M; Clini, E; Tonelli, R; Fantini, R; Mussini, C; Meschiari, M; Guaraldi, G; Cossarizza, A; Alfano, G; Girardis, M; Gibellini, Lara
abstract

Background- The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID19. Tocilizumab and Anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods- The association between therapy with Tocilizumab or Anakinra and in-hospital mortality was assessed in consecutive adult COVID19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who receive to those who did not receive Tocilizumab or Anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with Tocilizumab or Anakinra and after patient matching. Results- Sixty-six patients who received immunotherapy (49 Tocilizumab, 17 Anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0,77, 95% CI 0,56-1,05, p=0,069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0,40, 95% CI 0,19-0,83, p=0,015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions- Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need of mechanical ventilation.

2021 - Endobronchial valve positioning for alveolar-pleural fistula following ICU management of severe COVID-19 pneumonia. [Articolo su rivista]
Donatelli, P; Trentacosti, F; Pellegrino, Mr; Tonelli, R; Bruzzi, G; Andreani, A; Cappiello, Gf; Andrisani, D; Gozzi, F; Mussini, C; Busani, S; Cavaliere, Gv; Girardis, M; Bertellini, E; Clini, E; Marchioni, A.
abstract

Background- Since December 2019 the outbreak of novel Coronavirus (Severe Acute Respiratory Sindrome-2, SARS-CoV2) has spread across the world. The main clinical consequences are respiratory failure even requiring mechanical ventilation, and pneumonia frequently sharing clinical and radiologic similarities to Acute Respiratory Distress Syndrome (ARDS). In this context the lung parenchyma is highly prone to ventilator-related injury, with pneumothorax and persistent air leak as the most serious adverse events. So far, endobronchial valve (EBV) positioning has proved efficacy in treating air leaks with high success rate. Case presentation- We report, for the first time, two cases of patients affected by SARS-CoV2-related pneumonia suffering from pneumothorax and persistent air leaks after invasive mechanical ventilation, and successfully treated through EBV positioning. Conclusions- Persistent air leaks may result from lung tissue damage due to a complex interaction between inflammation and ventilator-related injury (VILI), especially in the advanced stages of ARDS. EBV positioning seems to be a feasible and effective least-invasive therapeutic option for caring this subset of patients.

2021 - Fibrotic idiopathic interstitial lung disease: the molecular and cellular key players. [Articolo su rivista]
Samarelli, A; Tonelli, R; Marchioni, A; Bruzzi, G; Gozzi, F; Andrisani, D; Castaniere, I; Manicardi, L; Moretti, A; Tabbì, L; Cerri, S; Beghe', B; Dominici, M; Clini, E.
abstract

Interstitial lung disease (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma culminating into inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies, can be di-vided into two groups: ILDs that have a known cause and those where the cause is unknown clas-sified as Idiopathic Interstitial Pneumonia (IIPs). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), Acute interstitial pneumonia (AIP), Desquamative Interstitial Pneumonia (DIP), Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review our aim is to de-scribe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung disease without known cause, would contribute to give a more accurate diagnosis to the patients, that would translate in a more effective treatment decision.

2021 - Herpes Simplex re-activation in patients with SARS-CoV2 pneumonia: a prospective observational study. [Articolo su rivista]
Franceschini, E; Cozzi-Lepri, A; Santoro, A; Bacca, E; Lancellotti, G; Menozzi, M; Gennari, W; Meschiari, M; Bedini, A; Orlando, G; Puzzolante, C; Digaetano, M; Milic, J; Codeluppi, M; Pecorari, M; Carli, F; Cuomo, G; Alfano, G; Corradi, L; Tonelli, R; De Maria, N; Busani, S; Biagioni, E; Coloretti, I; Guaraldi, G; Sarti, M; Luppi, M; Clini, E; Girardis, M; Gyssens, I; Mussini, C.
abstract

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care unit have been published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: We conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: Of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs 49.0%, p 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs 22.4%, p 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR=5.13, 95% CI:1.36-19.32, p=0.016). The effect size was larger when restricting to participants who were treated with high dose of steroids while there was no evidence to support an association with use of tocilizumab. Conclusions: Our study shows a high incidence of HSV-1 reactivation both virologically and clinically in patients with SARS-CoV-51 2 severe pneumonia, especially in those treated with steroids.

2021 - In memoriam Claudio F. Donner. [Articolo su rivista]
Clini, E.
abstract

Not available

2021 - Inspiratory effort and lung mechanics in spontaneously breathing patients with acute respiratory failure due to COVID-19. A matched control study. [Articolo su rivista]
Tonelli, R; Busani, S; Tabbì, L; Fantini, R; Castaniere, I; Biagioni, E; Mussini, C; Girardis, M; Clini, E; Marchioni, A.
abstract

Several physical and biological mechanisms can drive progression between the different phases of lung injury due to SARS-CoV-2 infection, thus modifying the mechanical properties and behavior of COVID-19 over time. In this research letter we have presented the findings of a registered clinical trial aimed at describing and comparing the inspiratory effort (primary outcome) and the breathing pattern of spontaneously breathing patients with ARF in COVID-19 and historically matched non-COVID-19 patients, either candidate to NIV. Moreover, we reported the response to a 2 hours NIV trial in the two groups. Spontaneously breathing COVID-19 at their early onset of acute respiratory failure with indication for NIV showed different mechanical characteristics and breathing pattern when compared with non-COVID-19.

2021 - Insufficienza respiratoria acuta e cronica (cap.21). [Capitolo/Saggio]
Bonsignore, Mr; Clini, E; Confalonieri, M; Costi, S; Crimi, C; Crisafulli, E; Longhini, F; Marchioni, A; Nava, S; Navalesi, P; Pisani, L; Spanevello, A; Tonelli, R.
abstract

Non disponibile

2021 - Interstitial lung disease and anti-myeloperoxidase antibodies: not a simple association [Articolo su rivista]
Sebastiani, Marco; Luppi, Fabrizio; Sambataro, Gianluca; Castillo Villegas, Diego; Cerri, Stefania; Tomietto, Paola; Cassone, Giulia; Bocchino, Marialuisa; Atienza-Mateo, Belen; Cameli, Paolo; Moya Alvarado, Patricia; Faverio, Paola; Bargagli, Elena; Vancheri, Carlo; Gonzalez-Gay, Miguel A; Clini, Enrico; Salvarani, Carlo; Manfredi, Andreina
abstract

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) 29 antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). 30 However, their role remains unclear and only 7-23% of these patients develops clinically overt vas- 31 culitis. We aimed to investigate the clinical, serological and radiological features, and prognosis of 32 anti-MPO-positive interstitial lung disease (ILD) patients. 33 Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing 34 serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clini- 35 cal data, lung function testing, chest high resolution computed tomography (HRCT) pattern, and 36 survival were recorded. 37 Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual 38 interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the pa- 39 tients’ survival. In fact, while the 52-week survival of the overall population was 71.4%±7.5, signif- 40 icantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. 41 Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7% and 41.5% 42 of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. 43 A careful clinical history and evaluation should be always performed in ILD patients with anti- 44 MPO antibodies to early identify patients developing a systemic rheumatic disease.

2021 - Looking ahead in Pulmonary Rehabilitation [Articolo su rivista]
Clini, E; Costi, S.
abstract

Not available

2021 - Molecular mechanisms and cellular contribution from lung fibrosis to lung cancer development. [Articolo su rivista]
Samarelli, ANNA VALERIA; Masciale, Valentina; Aramini, Beatrice; Pamela Colò, Georgina; Tonelli, Roberto; Marchioni, Alessandro; Bruzzi, Giulia; Gozzi, Filippo; Andrisani, Dario; Castaniere, Ivana; Manicardi, Linda; Moretti, Antonio; Tabbì, Luca; Guaitoli, Giorgia; Cerri, Stefania; Dominici, Massimo; Clini, Enrico
abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung 28 disease (ILD) of unknown etiology, with a median survival of 2-4 years from the time of diagnosis. 29 Although IPF has unknown etiology by definition, there have been identified several risks factors 30 increasing the probability of the onset and progression of the disease in IPF patients such as cigarette 31 smoking and environmental risks factors associated to domestic and occupational exposure. Among 32 them, cigarette smoking together with concomitant emphysema might predispose IPF patients to 33 lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer 34 development. To this purpose, IPF and LC share several cellular and molecular processes driving 35 the progression of both pathologies such as fibroblast transition proliferation and activation, endo- 36 plasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose 37 the IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed 38 as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target 39 molecular pathway. In this review our aim is to describe the updated studies on common cellular 40 and molecular mechanisms between IPF and lung cancer, whose knowledge might help to find 41 novel therapeutic targets for this disease combination.

2021 - Pulmonary stretch and lung mechanotransduction: Implications for progression in the fibrotic lung [Articolo su rivista]
Marchioni, A; Tonelli, R; Cerri, S; Castaniere, I; Andrisani, D; Gozzi, F; Bruzzi, G; Manicardi, L; Moretti, A; Demurtas, J; Baroncini, S; Andreani, A; Cappiello, G; Busani, S; Fantini, R; Tabbì, L; Samarelli, A; Clini, E.
abstract

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity, surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with as34 sociated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review we aim at summarizing the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.

2021 - Rehabilitative practice in Europe: roles and competencies of physiotherapists. Are we learning something new from COVID-19 pandemic? [Articolo su rivista]
Polastri, M; Lazzeri, M; Jacome, C; Vitacca, M; Costi, S; Clini, E; Marques, A.
abstract

Not available

2021 - Rituximab for the treatment of acute onset Interstitial Lung Disease in primary Sjogren's syndrome [Articolo su rivista]
Klinowski, G; Gozzi, F; Trentacosti, F; Andrisani, D; Sebastiani, M; Clini, E.
abstract

Not available

2021 - Routine Use of Immunosuppressants is Associated with Mortality in Hospitalised Patients with Covid-19 [Articolo su rivista]
Myint, P; Carter, B; Barlow-Pay, Fa; Short, R; Einarsson, A; Bruce, E; Mccarthy, K; Verduri, A; Collins, J; Hesford, J; Rickard, F; Mitchell, E; Holloway, M; Mcgovern, A; Vilches-Moraga, A; Braude, P; Pearce, L; Stechman, M; Price, A; Quinn, T; Clini, E; Moug, S; Hewitt, J.
abstract

Background: Whilst there has been some literature on impact of SAR viruses in severely immunosuppressed, less is known about the link between general usage of immunosuppressants and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, carried out in ten UK and one Italian hospitals. Data were collected between 27th February and 28th April by trained data collectors and included all non-selected consecutive admissions with Covid-19. Type and dosage of immunosuppressant use were collected along with other covariate data. The primary outcome was the time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-7 mortality and the time-to-discharge (described as the length of stay). Data were analysed with a mixed-effects, Cox proportional hazards and Logistic regression models using non-users of immunosuppressants as the reference group. Results: 1184 patients were eligible to be included. The median (IQR) age was 74(63-81) and 676(58%) were male, and 299(25.3%) died in hospital. Most patients exhibited at least one comorbidity, and 113(~10%) were on immunosuppressants. We found that any immunosuppressant use was associated with increased mortality: aHR 1.89,95%CI:1.31,2.71 (time to mortality) and aOR 1.90,95%CI:1.16-3.10 (7-day mortality). There appeared to be a direct and linear dose-response relationship regardless of the agent used. Conclusion: Low threshold to seek medical advice and close monitoring of worsening symptoms should be exercised in those who take immunosuppressants regardless of their indication.

2021 - Spontaneous breathing and evolving phenotypes of lung damage in patients with COVID-19. [Articolo su rivista]
Tonelli, R; Marchioni, A; Tabbì, L; Fantini, R; Busani, S; Castaniere, I; Andrisani, D; Gozzi, F; Bruzzi, G; Manicardi, L; Demurtas, J; Andreani, A; Cappiello, G; Samarelli, A; Clini, E.
abstract

The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual’s excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type.

2021 - Subclinical Atherosclerosis at Peripheral Arteries in Obese Individuals. [Articolo su rivista]
Farinetti, A; Castaniere, I; Clini, E; Migaldi, M; Gelmini, R; Scaringi Raspagliesi, F; Ara, N; Serra, F; Spatafora, F; Genazzani, A; Mattioli, Av.
abstract

Evidence on relationship between obesity and peripheral arterial disease (PAD) are controversial. The aim of the present study is to evaluate the presence of subclinical atherosclerosis at all level of the explorable vascular segments with a systematic method in a selected population of young obese submitted to a comprehensive rehabilitation course. A group of 50 consecutive morbidly obese (BMI>30) was included. All patients underwent Doppler evaluation including intima media thickness (IMT) and presence/absence of plaques. We found that vessels in the upper segment of the body demonstrate the presence of thickening and/or plaques at the level of the carotid segments but not of the subclavian arteries. The IMT of the right Common Carotid Artery (CCA) (1.49 + 1.38 versus 0.62 + 0.23; p=0.037) and of the left CCA (1.66 + 1.89 versus 0.45 + 0.26; p=0.034) was greater in patients. Vessels of the lower segment demonstrate the presence of thickening and/or plaques at the iliac but not at femoral level. The control group did not present vessel thickening at any level. In conclusions asymptomatic vascular damage may be present in different segment of peripheral vessels, thus suggesting an early risk for developing an overt vascular disease over time in obese.

2021 - Subclinical liver fibrosis in patients with idiopathic pulmonary fibrosis [Articolo su rivista]
Cocconcelli, E; Tonelli, R; Abbati, G; Marchioni, A; Castaniere, I; Pelizzaro, F; Russo, Fp; Vegetti, A; Balestro, E; Pietrangelo, A; Richeldi, L; Luppi, F; Spagnolo, P; Clini, E; Cerri, S.
abstract

Background - Data on the presence of subclinical fibrosis across multiple organs in patients with idiopathic lung fibrosis (IPF) are lacking. Our study aimed at investigating through hepatic transient elastography (HTE) the prevalence and clinical impact of subclinical liver fibrosis in a cohort of patients with IPF. Methods - Patients referred to the Centre for Rare Lung Disease of the University Hospital of Modena (Italy) from March 2012 to February 2013with established diagnosis of IPF and without a documented history of liver diseases were consecutively enrolled and underwent HTE. Based on hepatic stiffness status as assessed through METAVIR score patients were categorized as “ with liver fibrosis ” (corresponding to a METAVIR score of F1-F4) and “ without liver fibrosis” (METAVIR F0). Potential predictors of liver fibrosis were investigated through logistic regression model among clinical and serological variables. The overall survival (OS) was assessed according to liver fibrosis and multivariate Cox regression analysis was used to identify independent predictors. Results - In 13 out of 37 patients (35%) with IPF a certain degree of liver fibrosis was documented.No correlation was found between liver stiffness and clinical-functional parameters. OS was lower in patients ‘ with liver fibrosis’ than in patients ‘ without liver fibrosis’ (median months 33[23-55] vs. 63[26-94], p=0.038). Patients ‘ with liver fibrosis’ presented a higher risk of death at seven years as compared to patients ‘without liver fibrosis’ (HR=2.6, 95%CI[1.003–6.7],p= 0.049). Higher level of AST to platelet ratio Index (APRI)was an independent predictor of survival (HR=4.52 95%CI[1.3–15.6], p=0.02). Conclusions - In our cohort, more than one third of IPF patients had concomitant subclinical liver fibrosis that negatively affected OS. These preliminary claims further investigation aimed at clarifying the mechanisms beyond multiorgan fibrosis and its clinical implication in patients with IPF.

2020 - An Italian consensus on pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process [Articolo su rivista]
Vitacca, Michele; Lazzeri, Marta; Guffanti, Enrico; Frigerio, Pamela; D'Abrosca, Francesco; Gianola, Silvia; Carone, Mauro; Paneroni, Mara; Ceriana, Piero; Pasqua, Franco; Banfi, Paolo; Gigliotti, Francesco; Simonelli, Carla; Cirio, Serena; Rossi, Veronica; Beccaluva, Chiara G.; Retucci, Mariangela; Santambrogio, Martina; Lanza, Andrea; Gallo, Francesca; Fumagalli, Alessia; Mantero, Marco; Castellini, Greta; Calabrese, Mariaconsiglia; Castellana, Giorgio; Volpato, Eleonora; Ciriello, Marina; Garofano, Marina; Clini, Enrico; Ambrosino, Nicolino; behalf of AIPO, On; Sip, Arir; and SIFIR, Aifi
abstract

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts’ opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

2020 - An Italian sacrifice to COVID-19 epidemic. [Articolo su rivista]
Nava, S; Tonelli, R; Clini, E.
abstract

In order to better understand the problem of “deaths on the field” of Italian doctors during the COVID-19 outbreak, we have performed a descriptive statistic of colleagues who died. Data have been extracted from the national federation of medical doctor website (FNOMCEO, https://portale.fnomceo.it) reporting the daily bulletin of deaths. The present report is based on the available information by April 27th 2020 as the latest update. Cross-check by each name/surname has been made on a web search across local press and the individual’s professional order to obtain any other useful information. We included only those who were active or called back from retirement (122/151).

2020 - COVID-19 and pulmonary rehabilitation: Preparing for phase three [Articolo su rivista]
Polastri, M; Nava, S; Clini, E; Vitacca, M; Gosselink, R.
abstract

Considering the expected high burden of respiratory, physical and psychological impairment following the acute phase of COVID-19, a huge number of patients should be referred early to a rehabilitation program. Pulmonary rehabilitation is an evidence-based, well recognized and widely accepted and available to cover these needs.

2020 - Early inspiratory effort assessment by esophageal manometry early predicts noninvasive ventilation outcome in de novo respiratory failure: a pilot study. [Articolo su rivista]
Tonelli, Roberto; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Pisani, Lara; Pellegrino, Maria Rosaria; DELLA CASA, Giovanni; D'Amico, Roberto; Girardis, Massimo; Nava, Stefano; Clini, Enrico M.; Marchioni, Alessandro
abstract

Rationale: The role of inspiratory effort has still to be determined as a potential predictors of non-invasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure (AHRF). Objectives: We explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients. Methods: Thirty consecutive patients with AHRF admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal changes in esophageal (ΔPes) and dynamic transpulmonary pressure (ΔPL), expiratory tidal volume, and respiratory rate were recorded on admission and 2-4-12-24 hours after NIV start, and were tested for correlation with outcomes. Measurements and Main Results: ΔPes and ΔPes/ΔPL were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n=18) compared to those who needed endotracheal intubation (n=12) [median=11 (IQR=8–15) cmH2O vs 31.5 (30–36) cmH2O, p<0.0001] while other variables differed later. ΔPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in ΔPes of 10 cmH2O or more after 2 hours of treatment was strongly associated to avoidance of intubation, and represented the most accurate predictor of treatment success (OR=15, 95%CI 2.8-110, p=0.001, AUC=0.97, 95%CI 0.91–1, p<0.0001). Conclusions: The magnitude of inspiratory effort relief as assessed by ΔPes variation within the first 2 hours of NIV was an early and accurate predictor of NIV outcome at 24 hours.

2020 - Echo-endoscopic appearance of mediastinal metastasis from papillary renal carcinoma. [Articolo su rivista]
Piro, R; Tonelli, R; Cavazza, A; Taddei, S; Clini, E; Facciolongo, N.
abstract

Not available

2020 - Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia [Articolo su rivista]
Franco, C; Facciolongo, N; Tonelli, R; Dongilli, R; Vianello, A; Pisani, L; Scala, R; Malerba, M; Carlucci, A; Negri, Ea; Spoladore, G; Arcaro, G; Tillio, Pa; Lastoria, C; Schifino, G; Tabbi', L; Guidelli, L; Guaraldi, G; Ranieri, M; Clini, E; Nava, S.
abstract

Introduction: The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyze the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU. Methods: In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analyzed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths. Results: Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalization. Data are reported for all patients (69.3% male), whose mean age was 68 (SD 13) years. The PaO2/FiO2 ratio at baseline was 152+79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. Conclusions: The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.

2020 - Handling and processing of blood specimens from patients with Covid-19 for safe studies on cell phenotype and cytokine storm [Articolo su rivista]
Cossarizza, Andrea; Gibellini, Lara; DE BIASI, Sara; LO TARTARO, Domenico; Mattioli, Marco; Paolini, Annamaria; Fidanza, Lucia; Bellinazzi, Caterina; Borella, Rebecca; Castaniere, Ivana; Meschiari, Marianna; Sita, Marco; Manco, Gianrocco; Clini, Enrico; Gelmini, Roberta; Girardis, Massimo; Guaraldi, Giovanni; Mussini, Cristina
abstract

The pandemic caused by SARS-CoV-2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, ISAC published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks.

2020 - High flow nasal therapy versus noninvasive ventilation as initial ventilatory strategy in COPD exacerbation: a multicenter non-inferiority randomized trial [Articolo su rivista]
Cortegiani, A; Longhini, F; Madotto, F; Groff, P; Scala, R; Crimi, C; Carlucci, A; Bruni, A; Garofalo, E; Raineri, Sm; Tonelli, R; Comellini, V; Lupia, E; Vetrugno, L; Clini, E; Giarratano, A; Nava, S; Navalesi, P; Gregoretti, C.
abstract

Background- The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. Methods- We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results- Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions- HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD.

2020 - High flow oxygen therapy during exercise training in COPD patients with chronic respiratory failure: a multicenter randomised trial. [Articolo su rivista]
Vitacca, Michele; Paneroni, Mara; Zampogna, Elisabetta; Visca, Dina; Carlucci, Annalisa; Cirio, Serena; Banfi, Paolo; Pappacoda, Gabriele; Trianni, Ludovico; Brogneri, Antonio; Belli, Stefano; Paracchini, Elena; Aliani, Maria; Spinelli, Vito; Gigliotti, Francesco; Lanini, Barbara; Lazzeri, Marta; Clini, Enrico; Ambrosino, Nicolino
abstract

Background. High-flow oxygen therapy (HFOT) improves exercise capacity, oxygen saturation and symptoms in severe COPD. We wondered whether additional HFOT during training was more effective than oxygen through a Venturi Mask (V-mask) in improving exercise capacity in people with COPD and chronic respiratory failure (CRF). Methods. Patients (n=171) were randomized to receive either HFOT or oxygen through a V-mask at iso inspiratory oxygen fraction during the same intensity exercise training program. Pre- and post-training endurance time (Tlim), six minutes walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel and Barthel Dyspnea Indices, COPD Assessment Test, Maugeri Respiratory Failure questionnaire and patient satisfaction were evaluated. Results. Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in the HFOT and V-mask groups, respectively. Exercise capacity significantly improved after training in both groups with similar patients’ satisfaction. The improvement in 6MWD, (with 18 meters as mean difference between groups) but not in Tlim, was significantly higher in the HFOT group (p=0.029). The minimal clinically important difference (MCID) of Tlim was reached by 44% of V-mask and 56% of HFOT patients (p=0.867), whereas the MCID of 6MWD post-training was reached by 51% of V-mask and 69% of HFOT patients respectively (p= 0.036). 

2020 - Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study [Articolo su rivista]
Vilches-Moraga, A.; Price, A.; Braude, P.; Pearce, L.; Short, R.; Verduri, A.; Stechman, M.; Collins, J. T.; Mitchell, E.; Einarsson, A. G.; Moug, S. J.; Quinn, T. J.; Stubbs, B.; McCarthy, K.; Myint, P. K.; Hewitt, J.; Carter, B.; Davey, C.; Jones, S.; Lunstone, K.; Cavenagh, A.; Evans, L.; Silver, C.; Telford, T.; Simmons, R.; Mutasem, T. E. J.; Singh, S.; Paxton, D.; Harris, W.; Galbraith, N.; Bhatti, E.; Edwards, J.; Duffy, S.; Kelly, J.; Murphy, C.; Bisset, C.; Alexander, R.; Garcia, M.; Sangani, S.; Kneen, T.; Lee, T.; Kyriakopoulos, G.; Thomas, M.; Tan, D.; Clini, E.; Bruce, E.; Rickard, F.; Balow-Pay, F.; Hesford, J.; Holloway, M.
abstract

Background: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. Methods: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. Results: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58–81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6–24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1–3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97–4.11); CFS 5, 3.77 (1.94–7.32); CFS 6, 4.04 (2.09–7.82); CFS 7, 2.16 (1.12–4.20); and CFS 8, 3.19 (1.06–9.56). Conclusions: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

2020 - Integrated intErventional bronchoscopy in the treatment of locally adVanced non-small lung cancER with central Malignant airway Obstructions: a multicentric REtrospective study (EVERMORE). [Articolo su rivista]
Marchioni, A; Andrisani, D; Tonelli, R; Piro, R; Andreani, A; Cappiello, Gf; Meschiari, E; Dominici, M; Bavieri, M; Barbieri, F; Taddei, S; Casalini, E; Falco, F; Gozzi, F; Bruzzi, G; Fantini, R; Tabbì, L; Castaniere, I; Facciolongo, N; Clini, E.
abstract

Objectives- Despite new therapeutic perspectives, the presence of central airways occlusion (CAO) in patients with locally advanced non-small cell lung cancer (NSCLC) is associated with poor survival. There is no clear evidence on the clinical impact of interventional bronchoscopy as a part of an integrated treatment to cure these patients. Materials and methods- This retrospective cohort study was conducted in two teaching hospitals over a 10 years period (January 2010-January 2020) comparing patients with NSCLC at stage IIIB and CAO at disease onset treated with chemotherapy/radiotherapy (standard therapy-ST) with those receiving interventional bronchoscopy plus ST (integrated treatment-IT). Primary outcome was 1-year survival. The onset of respiratory events, symptoms-free interval, hospitalization, need for palliation, and overall mortality served as secondary outcomes. Results- A total of 100 patients were included, 60 in the IT and 40 in the ST group. Unadjusted Kaplan-Meier estimates showed greater effect of IT compared to ST on 1-year survival (HR=2.1 95%CI[1.1-4.8], p=0.003). IT showed a significantly higher survival gain over ST in those patients showing KRAS mutation (7.6 VS 0.8 months,<0.0001), a lumen occlusion >65% (6.6 VS 2.9 months,<0.001), and lacking the involvement of left bronchus (7 VS 2.3 months,<0.0001). Compared to ST, IT also showed a favorable difference in terms of new hospitalizations (p=0.03), symptom-free interval (p=0.02), and onset of atelectasis (p=0.01). Conclusions- In patients with NSCLC stage IIIB and CAO, additional interventional bronchoscopy might impact on 1-year survival. Genetic and anatomic phenotyping might allow identifying those patients who may gain life expectancy from the endoscopic intervention.

2020 - Janus-faced amiodarone-induced pneumopathy [Articolo su rivista]
Cerri, Stefania; Tonelli, Roberto; Faverio, Paola; Sverzellati, Nicola; Clini, Enrico; Luppi, Fabrizio
abstract

The authors describe a patient showing bilateral, peripheral, predominantly basal ground-glass and reticular opacities consistent with a non-specific interstitial pneumonia (NSIP) radiological pattern. This was followed by the occurrence of two nodules that progressively decreased in size after oral steroids had been given and therefore they were interpreted as an unusual manifestation of amiodarone-related pulmonary toxicity (APT).

2020 - Joint Statement on the Role of Respiratory Rehabilitation in the COVID-19 Crisis: The Italian Position Paper [Articolo su rivista]
Vitacca, M; Carone, M; Clini, E; Paneroni, M; Lazzeri, M; Lanza, A; Privitera, E; Pasqua, F; Gigliotti, F; Castellana, G; Banfi, P; Guffanti, E; Santus, P; Ambrosino, N.
abstract

Due to an exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian healthcare system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians coming from different specialties (intensivists or pneumologists and infectivologists), while respiratory therapists and nurses have been recruited to work on and on with rest. However, due to still limited and evolving knowledge of COVID-19 disease, there are little recommendations for need in respiratory rehabilitation and physiotherapy interventions. The presentation of this manuscript is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning in COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which were described in this paper to face with the emergency.

2020 - Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia - challenges, strengths, and opportunities in a global health emergency. [Articolo su rivista]
Ferrari, D; Milic, J; Tonelli, R; Ghinelli, F; Meschiari, M; Volpi, S; Faltoni, M; Franceschi, G; Iadisernia, V; Yaacoub, D; Ciusa, G; Bacca, E; Rogati, C; Tutone, M; Burastero, G; Raimondi, A; Menozzi, M; Franceschini, E; Cuomo, G; Corradi, L; Orlando, G; Santoro, A; Di Gaetano, M; Puzzolante, C; Carli, F; Borghi, V; Bedini, A; Fantini, R; Tabbì, L; Castaniere, I; Busani, S; Clini, E; Girardis, M; Sarti, M; Cossarizza, A; Mussini, C; Mandreoli, F; Missier, P; Guaraldi, G.
abstract

Aims- The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia. Methods- This was an observational study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients’ medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO 2 /FiO 2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome. Results- A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth “boosted mixed model” included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example. Conclusion- This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.

2020 - Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with Covid-19 pneumonia. [Articolo su rivista]
De Biasi, S; Meschiari, M; Gibellini, L; Bellinazzi, C; Borella, R; Fidanza, L; Gozzi, L; Iannone, A; Lo Tartaro, D; Mattioli, M; Paolini, A; Menozzi, M; Milić, J; Franceschi, G; Fantini, R; Tonelli, R; Sita, M; Sarti, M; Trenti, T; Brugioni, L; Cicchetti, L; Facchinetti, F; Pietrangelo, A; Clini, E; Girardis, M; Guaraldi, G; Mussini, C; Cossarizza, A.
abstract

We provide an in-depth investigation of the T cell compartment and functionality, cytokine production and plasma levels in a total of 39 patients affected by Covid-19 pneumonia. At admission, patients were lymphopenic; for all, SARS-CoV-2 was detected in a nasopharyngeal swab specimen by real-time RT-PCR, and pneumonia was subsequently confirmed by X-rays. Detailed 18-parameter flow cytometry coupled with unsupervised data analysis revealed that patients showed similar percentages of CD4+ and CD8+ T cells, but a decreased absolute number in both populations. For CD4+ T lymphocytes, we found a significant decrease in the number of naïve, central and effector memory cells and an increased percentage of terminally differentiated cells, regulatory T cells, and of those that were activated or that were expressing PD1 and CD57 markers. Studies on chemokine receptors and lineage-specifying transcription factors revealed that, among CD4+ T cells, patients displayed a lower percentage of cells expressing CCR6 or CXCR3, and of those co-expressing CCR6 and CD161, but higher percentages of 62 CXCR4+ or CCR4+ cells. No differences were noted in the expression of T-bet or GATA-3. Analyses of patients' CD8+ T cells showed decreased numbers of naïve and central memory and increased amounts of activated cells, accompanied by increased percentages of activated cells and of lymphocytes expressing CD57, PD1, or both. CD8+ T cells expressed lower percentages of CCR6+, CXCR3+ or T-bet+ cells and of CXCR3+,T-bet+ or CCR6+,CD161+ lymphocytes. We also found higher percentages of cells expressing CCR4+, CXCR4 or GATA-3. Analyses of lymphocyte proliferation revealed that terminally differentiated CD4+ and CD8+ T cell from patients had a lower proliferative index than controls, whereas cellular bioenergetics, measured by the quantification of mitochondrial oxygen consumption and extracellular acidification rate, was similar in CD4+ T cells from both groups. We measured plasma level of 31 cytokines linked to inflammation, including T helper (TH)type-1 and TH2 cytokines, chemokines, galectins, pro- and anti-inflammatory mediators, finding that most were dramatically increased in Covid-19 patients, confirming the presence of a massive cytokine storm. Analysis of the production of different cytokines after stimulation by anti-CD3/CD28 monoclonal antibodies revealed that patients not only had a high capacity to produce tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2, but also showed a significant skewing of CD4+ T cells towards the TH17 phenotype. A therapeutic approach now exists based on the administration of drugs that block IL-6pathway, and seems to improve the disease. IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung and are heavily involved in the pathogenesis of Covid-19. We show here that a skewing of activated T cells towards the TH17 functional phenotype exists in Covid-19 patients. We therefore suggest that blocking the IL-17 pathway by biological drugs that are already used to treat different pathologies could provide a novel, additional strategy to improve the health of patients infected by SARS-CoV-2.

2020 - Never Give Up: lesson learned from a severe COVID-19 patient. [Articolo su rivista]
Tonelli, Roberto; Iattoni, Andrea; Girardis, Massimo; De Pietri, Lesley; Clini, Enrico; Mussini, Cristina
abstract

We here report the clinical course of a 72-year old Caucasian male (M.A.) admitted for SARS-CoV2 pneumonia at our University Hospital in Modena. A multidisciplinary medical staff composed by different specialists (infectious diseases, pulmonology, intensive care) was in charge for caring and assuming shared clinical decisions.

2020 - Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople) [Articolo su rivista]
Carter, B.; Collins, J. T.; Barlow-Pay, F.; Rickard, F.; Bruce, E.; Verduri, A.; Quinn, T. J.; Mitchell, E.; Price, A.; Vilches-Moraga, A.; Stechman, M. J.; Short, R.; Einarsson, A.; Braude, P.; Moug, S.; Myint, P. K.; Hewitt, J.; Pearce, L.; Mccarthy, K.; Davey, C.; Jones, S.; Lunstone, K.; Cavenagh, A.; Silver, C.; Telford, T.; Simmons, R.; Holloway, M.; Hesford, J.; El Jichi Mutasem, T.; Singh, S.; Paxton, D.; Harris, W.; Galbraith, N.; Bhatti, E.; Edwards, J.; Duffy, S.; Kelly, J.; Murphy, C.; Bisset, C.; Alexander, R.; Garcia, M.; Sangani, S.; Kneen, T.; Lee, T.; Mcgovern, A.; Guaraldi, G.; Clini, E.
abstract

Background: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. Aim: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. Methods: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. Findings: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51–0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47–1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37–0.66). Conclusion: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

2020 - Obstructive sleep apnea and blood pressure in young hypertensives: does it matter? [Articolo su rivista]
Bonsignore, Maria Rosaria; Barbera, Calogero; Clini, Enrico.
abstract

Given the strong relationship between OSA and high Blood Pressure documented by a large amount of literature, occurrence of OSA in secondary hypertension of the young should be studied.

2020 - Pneumonic versus Nonpneumonic Exacerbations of Chronic Obstructive Pulmonary Disease. [Articolo su rivista]
Crisafulli, E; Manco, A; Ferrer, M; Huerta, A; Micheletto, C; Girelli, D; Clini, E; Torres, A.
abstract

Patients with chronic obstructive pulmonary disease (COPD) often suffer acute exacerbations (AECOPD) and community-acquired pneumonia (CAP), named nonpneumonic and pneumonic exacerbations of COPD, respectively. Abnormal host defense mechanisms may play a role in the specificity of the systemic inflammatory response. Given the association of this aspect to some biomarkers at admission (e.g., C-reactive protein), it can be used to help to discriminate AECOPD and CAP, especially in cases with doubtful infiltrates and advanced lung impairment. Fever, sputum purulence, chills, and pleuritic pain are typical clinical features of CAP in a patient with COPD, whereas isolated dyspnea at admission has been reported to predict AECOPD. Although CAP may have a worse outcome in terms of mortality (in hospital and short term), length of hospitalization, and early readmission rates, this has only been confirmed in a few prospective studies. There is a lack of methodologically sound research confirming the impact of severe AECOPD and COPD + CAP. Here, we review studies reporting head-to-head comparisons between AECOPD and CAP + COPD in hospitalized patients. We focus on the epidemiology, risk factors, systemic inflammatory response, clinical and microbiological characteristics, outcomes, and treatment approaches. Finally, we briefly discuss some proposals on how we should orient research in the future.

2020 - Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Sdanganelli, Antonia; Gozzi, Filippo; Musarò, Lorenzo; Fantini, Riccardo; Tabbì, Luca; Andreani, Alessandro; Cappiello, Gaia; Costi, Stefania; Castaniere, Ivana; Clini, Enrico
abstract

Introduction- Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not been yet elucidated. Methods- An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. Results- chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC=0.92 p<0.0001). Conclusions- Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

2020 - Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): A structured summary of a study protocol [Articolo su rivista]
Marietta, M; Vandelli, P; Mighali, P; Vicini, R; Coluccio, V; D'Amico, R; Aschieri, D; Brugioni, L; Clini, E; Codeluppi, M; Imberti, D; Magnacavallo, A; Meschiari, M; Mussini, C; Orlando, S; Pinelli, G; Pietrangelo, A; Sarti, L; Silva, M.
abstract

To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study.

2020 - Response Letter to Tuffet S, et al. and to Michard F, et al. [Articolo su rivista]
Tonelli, R; Tabbì, L; Fantini, R; Castaniere, I; Gozzi, F; Busani, S; Nava, S; Clini, E; Marchioni, A
abstract

Not available

2020 - Response letter to Spinelli E, et al. and Jha [Articolo su rivista]
Tonelli, R; Castaniere, I; Fantini, R; Tabbì, L; Busani, S; Pisani, L; Nava, S; Clini, E; Marchioni, A.
abstract

Not available

2020 - Surfactant replacement might help recovery of low-compliance lung in severe COVID-19 pneumonia. [Articolo su rivista]
Busani, S; Dall’Ara, L; Tonelli, R; Clini, E; Munari, E; Venturelli, S; Meschiari, M; Guaraldi, G; Cossarizza, A; Ranieri, Mv; Girardis, M.
abstract

It has been hypothesized that there is a reduced AT2 cells number with low ability to synthesize and secrete endogenous surfactant in COVID-19 patients. To our knowledge, exogenous surfactant replacement has not been described so far in COVID-19 patients. We here report five cases of critically ill COVID-19 undergoing exogenous surfactant instillation through the airways.

2020 - The Ideal Candidate (chapter 19). [Capitolo/Saggio]
de Blasio, Francesca; Mesquita, Rafael; Clini, Enrico
abstract

Impairments in balance and an increased risk of falling are common in people with COPD. This chapter provides an overview of best practices in balance assessment and fall risk management and implications for pulmonary rehabilitation. It reviews the current available research on balance impairments in individuals with chronic lung disease, including a discussion of the relevant evidence for guiding the choice of balance assessment measure in people with COPD. It also synthesizes the literature on balance training as part of pulmonary rehabilitation and provides examples of effective exercise programs for this purpose.

2020 - The Multi-morbidity Patient (chapter 35). [Capitolo/Saggio]
Tonelli, Roberto; Crisafulli, Ernesto; Costi, Stefania; Clini, Enrico.
abstract

The patients with chronic obstructive pulmonary disease (COPD) are elderly and complex individuals with comorbidities (multi-morbidity COPD), that reflect the coexistence of other medical conditions alongside their established lung and airways impairment. The identification of these associated conditions represents an important step towards the characterization of the patients’ disabilities and to an appropriate referral for comprehensive rehabilitation. The literature suggests that the number of comorbidities does not affect adherence or outcomes of pulmonary rehabilitation in multi-morbidity COPD patients. Notwithstanding, specific coexisting conditions may have a peculiar impact on the extent of the gains provided by the rehabilitation course. To optimize rehabilitation, clinicians should be aware of any specific needs associated with complex multi-morbidity COPD patients.

2020 - The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study [Articolo su rivista]
Hewitt, J; Carter, B; Vilches-Moraga, A; Quinn, Tj; Braude, P; Verduri, A; Pearce, L; Stechman, M; Short, R; Price, A; Collins, J; Bruce, E; Einarrson, A; Rickard, F; Mitchell, E; Holloway, M; Hesford, J; Barlow-Pay, F; Clini, E; Myint, Pk; Moug, Sj; McCarthy, K.
abstract

Background: The COVID-19 pandemic has placed unprecedented strain on health care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. The Cope Study (COVID-19 in Older People) was an observational cohort study designed to address this evidence gap. Methods: All adults, regardless of age, admitted consecutively with COVID-19 from 10 UK and one Italian hospital had demographic and diagnostic data collected. Frailty was assessed using the Clinical Frailty Score (CFS). The primary endpoint was in-hospital mortality (time to mortality and 7 day mortality) and time to discharge as the secondary outcome. Data were gathered between 27th February and 28th of April 2020. Data was analysed with a mixed-effects, Cox proportional hazards and Logistic regression models. Findings: Data were collected on 1564 people with a confirmed diagnosed of COVID-19: median age was 74 years old (IQR, 61-83), 901 were male (57.7%), 425 (27.2%) died in hospital. Using the Clinical Frailty Scale, the number of people who were classed as mildly frail or above was 51.1%. Both time to mortality and time to discharge worsened with increasing frailty, after adjustment for: age; sex; smoking; and comorbidities. The adjusted Hazard Ratio (aHR, 95%CI) for CFS 3-4 (managing well, vulnerable), 5-6 (mildly frail and frail) and 7-9 (severely frail, very severely frail and terminally ill) compared to CFS 1-2 (very fit, well) were 1.64 (1.06-2.55), 2.02 (1.27-3.20) and 2.66 (1.68-4.21) for time to mortality and 0.97 (0.79-1.19), 0.69 (0.53-0.89) and 0.63 (0.47-0.83) for the time to discharge. Interpretation: In a large adult population of people with COVID-19, worsening frailty was associated with progressively increasing mortality and later discharge from hospital. These data provide evidence that frailty is not dependent on age and that the Clinical Frailty Scale can inform decision making about medical care in the adult COVID-19 hospital population.

2020 - The influence of ACE inhibitors and ARBs on hospital length of stay and survival in people with COVID-19 [Articolo su rivista]
Philip Braude, P; Carter, B; Short, R; Vilches-Moraga, A; Verduri, A; Pearce, L; Price, A; Quinn, Tj; Stechman, M; Collins, J; Bruce, E; Einarsson, A; Rickard, F; Mitchell, E; Holloway, M; Hesford, J; Barlow-Pay, F; Clini, E; Myint, Pk; Moug, S; McCarthy, K; Hewitt, J.
abstract

Objective During the COVID-19 pandemic the continuation or cessation of angiotensin- converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been contentious. Mechanisms have been proposed for both beneficial and detrimental effects. Recent studies have focused on mortality with no literature having examined length of hospital stay. The aim of this study was to determine the influence of ACEi and ARBs on COVID-19 mortality and length of hospital stay. Methods COPE (COVID-19 in Older People) is a multicenter observational study including adults of all ages admitted with either laboratory or clinically confirmed COVID-19. Routinely generated hospital data were collected. Primary outcome: mortality; secondary outcomes: Day-7 mortality and length of hospital stay. A mixed-effects multivariable Cox’s proportional baseline hazards model and logistic equivalent were used. Results 1371 patients were included from eleven centres between 27th February to 25th April 2020. Median age was 74 years [IQR 61-83]. 28.6% of patients were taking an ACEi or ARB. There was no effect of ACEi or ARB on inpatient mortality (aHR=0.85, 95%CI 0.65-1.11). For those prescribed an ACEi or ARB, hospital stay was significantly reduced (aHR=1.25, 95%CI 1.02-1.54, p=0.03) and in those with hypertension the effect was stronger (aHR=1.39, 95%CI 1.09-1.77, p=0.007). Conclusions Patients and clinicians can be reassured that prescription of an ACEi or ARB at the time of COVID-19 diagnosis is not harmful. The benefit of prescription of an ACEi or ARB in reducing hospital stay is a new finding.

2020 - Tocilizumab in patients with severe COVID-19: a retrospective cohort study [Articolo su rivista]
Guaraldi, G; Meschiari, M; Cozzi-Lepri, A; Milic, J; Tonelli, R; Menozzi, M; Franceschini, E; Cuomo, G; Orlando, G; Borghi, V; Santoro, A; Di Gaetano, M; Puzzolante, C; Carli, F; Bedini, A; Corradi, L; Fantini, R; Castaniere, I; Tabbì, L; Girardis, M; Tedeschi, S; Giannella, M; Bartoletti, M; Pascale, R; Dolci, G; Brugioni, L; Pietrangelo, A; Cossarizza, A; Pea, F; Clini, E; Salvarani, C; Massari, M; Viale, Pl; Mussini, C.
abstract

Background- There is no approved therapy for COVID-19 pneumonia. The aim of this multicentre cohort study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and/or death in patients with severe COVID-19 pneumonia who received standard of care (SoC) treatment. Methods- The TESEO Cohort Study is a retrospective, multicentre observational cohort study of patients with COVID-19 severe pneumonia treated with SoC with or without tocilizumab using intravenous (IV) or subcutaneous (SC) formulations, identifying respectively treated and comparator groups. Survival analysis was performed with participants’ follow-up accruing from the date of entry into clinics until initiation of invasive mechanical ventilation or death, used as a composite outcome. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for gender, age and baseline Sequential Organ Failure Assessment (SOFA) score. Findings- Of 544 patients included, 179 patients were treated with tocilizumab: 88 with the IV (16.1%) and 91 with SC formulation (16.7%). Mortality was significantly higher in the comparator group (20%) as opposed to tocilizumab IV (6.8%) and tocilizumab SC (7.7%) (p<0.001). A reduced risk of invasive mechanical ventilation/death was shown for participants treated with tocilizumab from fitting a Cox regression analysis adjusted for gender, age and SOFA score (aHR=0.61, 95% CI:0.40-0.92; p=0.02). We found no evidence for a difference between IV and SC administration route of tocilizumab. With regards to the mortality endpoint alone, a reduced risk was observed comparing tocilizumab with the comparator group (aHR=0.38 95% CI:0.17-0.83, p=0.02) . Interpretation- Tocilizumab, regardless of IV or SC administration may be capable of reducing invasive mechanical ventilation or death in severe COVID-19 pneumonia. Our observations should be confirmed in randomised studies. Funding- This study was not funded.

2020 - Two fatal cases of acute liver failure due to HSV-1 infection in COVID-19 patients following immunomodulatory therapies. [Articolo su rivista]
Busani, S; Bedini, A; Biagioni, E; Serio, L; Tonelli, R; Meschiari, M; Franceschini, E; Guaraldi, G; Cossarizza, A; Clini, E; Maiorana, A; Gennari, W; De Maria, N; Luppi, M; Mussini, C; Girardis, M.; Gibellini, Lara
abstract

We reported two fatal cases of acute liver failure secondary to Herpes Simplex Virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy. Screening for and prompt recognition of Herpes Simplex Virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentially relevant clinical consequences.

2020 - Unusual effectiveness of systemic steroids in Whipple disease. [Articolo su rivista]
Fontana, Matteo; Cerri, Stefania; Bernardelli, Giuditta; Brugioni, Lucio; Clini, Enrico; Tonelli, Roberto.
abstract

Not available

2020 - Ventilatory support and mechanical properties of the fibrotic lung acting as a “squishy ball” [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Rossi, Giulio; Spagnolo, Paolo; Luppi, Fabrizio; Cerri, Stefania; Cocconcelli, Elisabetta; Pellegrino, Maria Rosaria; Campana, Davide; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Ball, Lorenzo; Malbrain, Manu L. N. G.; Pelosi, Paolo; Clini, Enrico
abstract

Protective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit. Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology. The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of “squishy ball lung”. The role of positive end-expiratory pressure is discussed, proposing a “lung resting strategy” as opposed to the “open lung approach”. The review also discusses the practical management of AE-ILD patients discussing illustrative clinical cases.

2020 - Ventilazione meccanica domiciliare (cap.26) [Capitolo/Saggio]
Vitacca, M; Marchioni, A; Tonelli, R; Clini, E.
abstract

Il capitolo descrive le principali indicazioni per l'indicazione e l'adozione della ventilazione meccanica domiciliare (VMD) nei pazienti affetti da sindrome da insufficienza respiratoria cronica.

2019 - A case of dyspnea: respiratory failure due to pulmonary arteriovenous malformation [Articolo su rivista]
Lucio, Brugioni; Chiara, Catena; Eugenio, Ferraro; Serena, Scarabottini; Francesca, Mori; Enrico, Clini
abstract

Pulmonary arteriovenous malformations (PAVMs) are abnormal communications between pulmonary arteries and veins. The clinical features suggestive of PAVMs are stigmata of right-to-left shunting (dyspnea, hypoxemia, cyanosis, cerebral embolism, brain abscess), unexplained hemoptysis, or hemothorax. We present a case of a young man who presented to the Emergency Department complaining of dyspnea, polycythemia, and persistent hypoxemia. Angio-computed tomographic scan of the chest detected multiple PAVMs. PAVMs are uncommon in the general population, but they represent an important consideration in the differential diagnosis of common pulmonary problems, including hypoxemia, pulmonary nodules, and hemoptysis.

2019 - A guide for respiratory physiotherapy postgraduate education - the presentation of a Harmonized Curriculum [Articolo su rivista]
Troosters, T; Langer, D; Burtin, C; Chatwin, M; Clini, E; Emtner, M; Gosselink, R; Grant, K; Inal-Ince, D; Lewko, A; Main, E; Oberwaldner, B; Pitta, F.
abstract

The design of a European (or global) curriculum for respiratory physiotherapy provides a platform for educational tracks in order to match specific educational programmes to the current consensus of what is expected from a trained respiratory physiotherapist. It also makes suggestions as to how the knowledge, skills and attitudes can be obtained and at which level they should be examined. Importantly, this curriculum also provides third parties (chest physicians, general practitioners, nurses, thoracic surgeons, intensivists, funders and patients) with a comprehensive description of what they can expect from a trained respiratory physiotherapist.

2019 - Arachidonic acid and docosahexaenoic acid metabolites in the airways of adults with cystic fibrosis: effect of docosahexaenoic acid supplementation. [Articolo su rivista]
Teopompi, Elisabetta; Risé, Patrizia; Pisi, Roberta; Buccellati, Carola; Aiello, Marina; Pisi, Giovanna; Tripodi, Candida; Fainardi, Valentina; Clini, Enrico; Chetta, Alfredo; Enrico Rovati, G.; Sala, Angelo
abstract

Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator (CFTR) protein. Several reports have indicated the presence of specific fatty acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of Specialized Pro-resolving Mediators (SPMs). We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 Chronic Obstructive Pulmonary Disease (COPD) subjects were collected and analyzed by LC/MS/MS and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. As compared to COPD patients, CF subjects showed increased concentrations of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and 15-hydroxyeicosatetraenoic acid (15-HETE), while the concentrations of DHA metabolites were not different in the two groups. After DHA supplementation, not only DHA/AA ratio and highly unsaturated fatty acid (HUFA) index were significantly increased (p < 0.05), but CF subjects showed a tendency toward a decrease in LTB4 and PGE2 and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels, together with a significantly reduction in 15-HETE. At the end of the washout period, LTB4, PGE2, 15-HETE, and 17OH-DHA tended to recover baseline values. As compared to baseline, 15-HETE/17OH-DHA ratio significantly changed after supplementation (p < 0.01). Our results showed that in CF patients an impairment in fatty acid metabolism, characterized by increase in AA metabolites and decrease in DHA, was partially corrected by DHA supplementation.

2019 - Atypical diagnosis for typical lung carcinoid [Articolo su rivista]
Piro, Roberto; Tonelli, Roberto; Taddei, Sofia; Marchioni, Alessandro; Musci, Giovanni; Clini, Enrico; Facciolongo, Nicola
abstract

Background - The diagnosis of lung typical carcinoid tumors results challenging when limited size and unfavorable sampling location is associated. It has been reported that bronchoscopy with endobronchial ultrasound (EBUS) significantly increases the diagnostic yield of peripheral nodules smaller than 2 cm. Case presentation - A 70-year-old Caucasian male complained of persistent fever and cough despite several antibiotic courses and steroid treatment. Chest radiology revealed the presence of a small single nodular opacity in the left upper lobe, whose standardized maximum uptake value (SUV) at fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) was significantly high (4.5). The patient underwent bronchial endoscopy but any appreciable sign of endobronchial or intramural involvement was detected. Only radial ultrasound-guided bronchoscopy (R-EBUS) allowed transbronchial sampling whose pathological analysis revealed a typical carcinoid tumor. The patients underwent surgical lobectomy and clinic-radiological follow was started. Conclusions- With this case we aim at stressing the importance of ultrasound in the diagnostic process of lung small peripheral carcinoid, especially if they present without mucosal or sub mucosal involvement.

2019 - Baseline exercise tolerance and perceived dyspnea to identify the ideal candidate to pulmonary rehabilitation: a risk chart in COPD patients. [Articolo su rivista]
COSTI, Stefania; Crisafulli, Ernesto; Trianni, Ludovico; BEGHE', Bianca; Faverzani, Silvia; Scopelliti, Giuseppe; Chetta, Alfredo; CLINI, Enrico
abstract

Background The appropriate criteria for patient selection are still a key issue in the clinical management of patients referred to pulmonary rehabilitation (PR). Methods We retrospectively analyzed the records of a wide population of 1470 outpatient or inpatients with chronic obstructive pulmonary disease (COPD) referred to standard PR at two specialized Italian centers. Two models of multivariate logistic regression were developed to test the predictive powers of baseline exercise tolerance, namely the distance walked in 6 minutes (6MWD), and of baseline dyspnea on exertion, measured by the modified Medical Research Council scale (mMRC), versus the minimal clinically important difference (MCID) for the same outcomes. Results- (p<0.001) of predicting a MCID change. Compared to the category of individuals with mMRC 0-1point, all the other categories (2, 3, and 4) also showed a higher probability (p<0.001) of predicting a MCID change. The incorporation of baseline categories of 6MWD and mMRC in a risk chart showed that the percentage of patients reaching MCID in both variables increased as the baseline level of 6MWD decreased and of mMRC increased. Conclusion- This study demonstrates that lower levels of exercise tolerance and greater perceived dyspnea on exertion predict achieving clinically meaningful changes for both these treatment outcomes following PR. A specific risk chart that integrates these two variables may help clinicians to select ideal candidates and best responders to PR.

2019 - Cardiac Diseases and respiratory consequences [Monografia/Trattato scientifico]
Clini, E; Roversi, S; Beghè, B; Fabbri, Lm.
abstract

• Literature indicates an important link between chronic obstructive lung disease, ischemic heart disease and heart failure. • The pathogenesis of the association is partially unclear, but probably recognized shared risk factors, such as smoke, altered local and systemic inflammatory response, and alteration in blood gases. • Patients with cardio-respiratory comorbidities have non-specific symptoms, and often a correct diagnosis is challenging. • The diagnosis of respiratory disease, as well as the treatment, should not generally deviate from international guidelines and indications, regardless of associated cardiac diseases. Similarly, cardiac diseases should be treated according to guidelines; caution may be advised for beta-blockers and amiodarone.

2019 - Clinical differences in sarcoidosis patients with and without lymphoma: a single-center retrospective cohort analysis. [Articolo su rivista]
Cerri, Stefania; Fontana, Matteo; Balduzzi, Sara; Potenza, Leonardo; Faverio, Paola; Luppi, Mario; Damico, Roberto; Spagnolo, Paolo; Clini, Enrico; Luppi, Fabrizio
abstract

We retrospectively reviewed the database of the “Center for Rare Lung Diseases” at the University Hospital of Modena to identify all subjects with a diagnosis of sarcoidosis between 1990 and 2013, with the aim to evaluate clinical, functional and serological differences related to the presence of lymphoma in sarcoidosis patients, as well as difference in survival. This study suggests the existence of clinical, radiological and serological differences in sarcoidosis with or without lymphoma syndrome. The knowledge of these differences seems important for a timely diagnosis and treatment. However, further prospective studies are required to confirm present observations.

2019 - Do not forget to assess the muscle integrity in COPD patients. [Articolo su rivista]
Cerri, S; Clini, E.
abstract

Not available

2019 - European Respiratory Society Guideline on Long-term Home Non-Invasive Ventilation for Management of Chronic Obstructive Pulmonary Disease. [Articolo su rivista]
Ergan, Begum; Oczkowski, Simon; Rochwerg, Bram; Carlucci, Annalisa; Chatwin, Michelle; Clini, Enrico; Elliott, Mark; GONZALEZ BERMEJO, Jesus; Hart, Nick; Lujan, Manel; Nasilowski, Jacek; Nava, Stefano; PEPIN, Jean-Louis; Pisani, Lara; Storre, Jan; Wijkstra, Peter; Boyd, Jeanette; Tonia, Thomy; Scala, Raffaele; Windisch, Wolfram
abstract

Background While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD), the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. Materials and methods The European Respiratory Society Task Force (TF) committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. Results The TF committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, (1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; (2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV (3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and (4) suggesting for using fixed pressure support as first choice ventilator mode. Conclusions Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The TF conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

2019 - Gender differences in chronic obstructive pulmonry disease: can be DRG-based diagnosis the best way for a right analysis ? [Articolo su rivista]
Nicolini, A; Garuti, G; Perazzo, T; Banfi, P; Clini, E.
abstract

Not available

2019 - Introduction of the harmonised respiratory physiotherapy curriculum. [Articolo su rivista]
Troosters, T; Tabin, N; Langer, D; Burtin, C; Chatwin, M; Clini, E; Emtner, M; Gosselink, R; Grant, K; Inal-Ince, D; Lewko, A; Main, E; Mitchell, S; Niculescu, A; Oberwaldner, B; Pitta, F.
abstract

The proposed curriculum describes the knowledge, skills and attitudes that must be mastered by a respiratory physiotherapist working with adults and/or children. It also provides indications for minimum clinical exposure, forms of learning and assessment.

2019 - Manual Massage Therapy for Patients with COPD: A Scoping Review. [Articolo su rivista]
Polastri, Massimiliano; Clini, Enrico; Nava, Stefano; Ambrosino, Nicolino
abstract

Background and objectives: Manual massage therapy is a therapeutic option for the treatment of several pathological conditions affecting the musculoskeletal system. It has been pointed out that massage might be beneficial for COPD patients thanks to therapeutic effects primarily related to hyperemia, increased both skin temperature and blood flow, and activation of the lymphatic system. The present study reports current evidence on the systemic effects of manual massage in patients with COPD. Materials and Methods: A scoping review was conducted on five major databases. The search went through all databases since their inception until December 2018. Results: Seventy-eight citations were retrieved; after the selection process was completed, seven articles were considered eligible. In patients receiving manual massage, improvements were observed in FEV1, dyspnea perception, and in the 6-minute walking test. Conclusions: To date the use of the manual massage in patients with COPD is not supported by substantial evidence in the literature: indeed, it is proposed as a therapeutic option in association with other interventions such as physical exercise.

2019 - Prognostication by concomitant organ failure in mechanically ventilated patients in ICU: important issue to face with [Articolo su rivista]
Beghè, B; Clini, E
abstract

Not available

2019 - Pulmonary Rehabilitation [Capitolo/Saggio]
de Blasio, Francesca; de Blasio, Francesco; Clini, Enrico
abstract

Disability in chronic respiratory diseases (CRD) represents the impact of the disease on the patient’s life. Chronic airway diseases, included but not limited to COPD, are leading this burden. Overall, the mobility-related dyspnea and the resulting decrease in exercise capacity substantially contribute to increased risk of disability, even after taking lung function impairment into account. Therefore, non-pharmacological interventions such as pulmonary rehabilitation (PR) might be particularly beneficial for these symptomatic patients to limit and to counteract the progressive loss of physical function and related problems. In this chapter we will discuss the most recent evidence related to the assessment of individual’s disability in this population, and we will describe the variety of methods used in the clinical process of care called PR. To date, PR results in substantial effectiveness when applied at the very early onset of disability in individuals suffering from CRD. Programme composition and strategies aimed at behavioural changes in the long-term appear the keys for success in the clinical practice.

2019 - Real-life comparison of Pirfenidone and Nintedanib in patients with Idiopathic Pulmonary Fibrosis: a 24-month assessment. [Articolo su rivista]
Cerri, Stefania; Monari, Matteo; Guerrieri, Aldo; Donatelli, Pierluigi; Bassi, Ilaria; Garuti , Martina; Luppi, Fabrizio; Betti, Sara; Bandelli, Giampiero; Carpano , Marco; Bacchi-Reggiani, Marialuisa; Tonelli, Roberto; Clini, Enrico; Nava, Stefano.
abstract

Background: Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce. Methods: We compared the efficacy of either pirfenidone (n=78) or nintedanib (n=28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n=36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded. Results: Over time, the decline in FVC and DLCO was significantly higher (p=0.0053 and p=0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups. Conclusion: This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.

2019 - Respiratory mechanics and diaphragmatic dysfunction in COPD patients who failed non-invasive mechanical ventilation [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Livrieri, Francesco; Bedogni, Sabrina; Ruggieri, Valentina; Pisani, Lara; Nava, Stefano; Clini, Enrico
abstract

Background. Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure. Methods. Twelve AECOPD with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017-2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end expiratory lung volume (EELV) were measured after 30 minutes of volume control mode MV. Subsequently transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 minutes of spontaneous breathing trial. Linear regression analysis and Pearson’s correlation coefficient served to assess associations. Results. Average Pdisniff was 23.3 (standard deviation, SD=29) cmH20 with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=-0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=-0.55, p=0.06), EELV (r=-0.4, p=0.3), airway resistance (r=-0.2, p=0.54), chest wall and total elastance (r=-0-01, p=0.96 and r=0.3, p=0.36 respectively). Significant linear inverse correlation was found between Pdi/Pdisniff and Pdisniff (r=-0.82, p=0.02). Conclusion. The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload.

2019 - Serial Ultrasound Assessment of Diaphragmatic Function and Clinical Outcome in Patients with Amyotrophic Lateral Sclerosis. [Articolo su rivista]
Fantini, Riccardo; Tonelli, Roberto; Castaniere, Ivana; Tabbì, Luca; Pellegrino, Maria Rosaria; Cerri, Stefania; Livrieri, Francesco; Giaroni, Francesco; Monelli, Marco; Ruggieri, Valentina; Fini, Nicola; Mandrioli, Jessica; Clini, Enrico; Marchioni, Alessandro; Stefania, Cerri
abstract

Background: Ultrasound (US) evaluation of the diaphragm may be a non-volitional useful tool in the clinical management of patients with ALS. Aim of the present study was then to evaluate the impact of serial assessment of ΔTmax index on clinical outcomes during the follow-up in these patients and to correlate non-volitional US indices and other volitional measures with these outcomes. Methods: A cohort of 39 consecutive patients with ALS was followed up to 24 months. At baseline and every 3-month spirometry (forced vital capacity-FVC), sniff inspiratory nasal pressure (SNIP), and US of the diaphragm (ΔTdi and ΔTmax) were recorded. These parameters were correlated with clinical outcomes (hypercapnia, nocturnal hypoventilation, NIV start in the following 6 month, and death within 1 year). Results: The occurrence of ΔTmax >0.75 during follow-up increased the risk for NIV (HR=5.6, p=0.001) and death (HR=3.7, p=0.0001) compared with patients with stable lower values. The evidence of diaphragmatic dysfunction, i.e. ΔTmax >0.75, occurs 3.2 month earlier than the onset of NIV. Moreover, ΔTmax >0.75 correlated with onset of nocturnal hypoventilation, NIV initiation within 6 months, and death within 12 months, similarly to FVC <50% predicted and better than other functional indices. Conclusions: Serial monitoring of diaphragmatic ΔTmax by US may be useful to predict initiation of NIV and death in patients with ALS. The occurrence of an abnormal ΔTmax value in the follow-up precedes the decision for starting NIV.

2019 - Subclinical atherosclerosis at peripheral arteries in obese subjects [Abstract in Rivista]
Farinetti, Alberto; Clini, Enrico; Migaldi, Mario; Gelmini, Roberta; Serra, Francesco; Spatafora, Francesco; Scaringi Raspagliesi, Flavia; Ara, Nicoletta
abstract

2019 - Three-year hospitalization and mortality in elderly smokers with COPD or CHF. [Articolo su rivista]
Beghé, B; Fabbri, Lm; Garofalo, M; Schito, M; Verduri, A; Bortolotti, M; Stendardo, M; Ruggieri, V; Fucili, A; Sverzellati, N; Della Casa, G; Maietti, E; Clini, E; Boschetto, P.
abstract

Background: In elderly smokers, COPD and CHF usually present with dyspnoea. COPD and CHF are associated almost invariably with concomitant chronic diseases which contribute to severity and prognosis. Objectives: We investigated similarities and differences in the clinical presentation, concomitant chronic diseases and risk factors for mortality and hospitalization at 3-year follow-up in elderly smokers/ex-smokers with a primary diagnosis of COPD or CHF recruited and followed in specialized centers. Methods: We examined 144 patients with COPD and 96 with CHF, ≥ 65 yrs, ≥20 pack/years, and measured CAT score, mMRC, NYHA, and Charlson Index, routine blood test, eGFR, HRCTscan, 6MWT. In addition, in each patient we actively searched for CHF, COPD, peripheral vascular disease, and metabolic syndrome. Results: COPD and CHF patients had mild to moderate disease, but the majority was symptomatic. Comorbidities were highly prevalent and often unrecognized in both groups. COPD and CHF patients had a similar risk of hospitalization and death at 3 years. Lower glomerular filtration rate, shorter 6MWT and ascending aorta calcification score ≥2 were independent predictors of mortality in COPD, whereas previous 12 month hospitalizations, renal disease and heart diameter were in CHF patients. Lower glomerular filtration rate value, higher CAT score and lower FEV1/FVC ratio were associated with hospitalization in COPD, whilst age, lower FEV1 % predicted and peripheral vascular disease were in CHF. Conclusions: There are relevant similarities and differences between patients with COPD and CHF even when admitted to specialized outpatient centers, suggesting that these patients should be manage in multidisciplinary units.

2018 - Acute exacerbation of Idiopathic Pulmonary Fibrosis: lessons learned from the Acute Respiratory Distress Syndrome [Articolo su rivista]
Marchioni, A; Tonelli, R; Ball, L; Fantini, R; Castaniere, I; Cerri, S; Luppi, F; Malerba, M; Pelosi, P; Clini, E.
abstract

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with the Acute Respiratory Distress Syndrome (ARDS), a very severe condition commonly treated in this setting. A review of the literature has been here conducted to underline similarities and differences for caring and managing patients with AE-IPF and ARDS. During AE-IPF, a diffuse alveolar damage and massive loss of aeration occurs, similarly to what is observed in patients with ARDS. Differently from ARDS, no studies have concluded yet on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in these patients, as well as the precise role of other types of respiratory assistance (e.g. ECMO) or innovative therapies (e.g. polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controverial and potentially associated with increased risk of serious adverse reactions. Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

2018 - An uncommon cause of hemoptysis: aortobronchial fistula. [Articolo su rivista]
Fontana, M; Tonelli, R; Gozzi, F; Castaniere, I; Marchioni, A; Fantini, R; Coppi, F; Natali, F; Rovatti, Elisabetta; Clini, E.
abstract

Background- Hemoptysis is a frequent sign of respiratory and non-respiratory diseases. While in most cases the underlying cause is rapidly identified, sometimes the real etiology might be misdiagnosed with dramatic delay in treatment. Case presentation- A 46-year-old man with hiatal hernia and a history of aortic surgery for aortic coarctation presented with dramatic episodes of hemoptysis and subsequent severe anemia (6,9 g/dl). Digestive and respiratory endoscopy resulted not exhaustive thus he underwent a contrast-enhanced computed tomography (CT) scan of the chest that showed an aneurysmal dilatation of the descending thoracic aorta with suspected aortobronchial fistula. He underwent cardiac surgery that confirmed the diagnosis and successfully treated the fistula. Conclusion- We briefly review the literature to raise clinical awareness on this uncommon cause of hemoptysis.

2018 - Assessment of Symptoms in Patients with COPD: Strengths and Limitations of Clinical Scores [Articolo su rivista]
Polastri, Massimiliano; Ambrosino, Nicolino; Vitacca, Michele; Nava, Stefano; Clini, Enrico.
abstract

Purpose of Review: Health questionnaires are valuable tools to quantify, in an objective and standardized manner, the impact of chronic obstructive pulmonary disease on the health status of patients and on their well-being, and to track changes over time.Therefore, filling out these questionnaires allows clinicians to obtain the necessary information that can be easily related to clinical outcomes. Recent Findings: Most importantly, symptoms’ assessment represents a very relevant part of these clinical tools when applied to patients suffering from chronic respiratory diseases. Comparing scores between visits is also indicative of the patient’s health status, as changes in quality of life are related to worse outcomes such as hospitalization and exacerbation. However, each respiratory questionnaire may be peculiar in catching specific aspects of a similar symptom (i.e., dyspnoea); therefore, different tools are not interchangeable or comparable.Summary: Detecting the minimal clinically important difference is a necessary evaluation procedure which affords the change inpatient’s management and directs the therapeutic action towards more active treatments.

2018 - Breathlessness, but not cough, suggests chronic obstructive pulmonary disease in elderly smokers with stable heart failure. [Articolo su rivista]
Roversi, S; Boschetto, P; Beghè, B; Schito, M; Garofalo, M; Stendardo, M; Ruggieri, V; Tonelli, R; Fucili, A; D'Amico, R; Banchelli, F; Fabbri, Lm; Clini, E.
abstract

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of heart failure (HF), but remains often undiagnosed, and we aimed to identify symptoms predicting COPD in HF. As part of an observational, prospective study, we investigated stable smokers with a confirmed diagnosis of HF, using the 8-item COPD-Assessment-Test (CAT) questionnaire to assess symptoms. All the items were correlated with the presence of COPD, and logistic regression models were used to identify independent predictors. 96 HF patients were included, aged 74, 33% with COPD. Patients with HF and COPD were more symptomatic, but only breathlessness when walking up a hill was an independent predictor of COPD (odds ratio=1.33, p=0.0484). Interestingly, COPD-specific symptoms such as cough and phlegm were not significant. Thus, in elderly smokers with stable HF, significant breathlessness when walking up a hill is most indicative of associated COPD, and may indicate the need for further lung function evaluation.

2018 - Endothelial dysfunction by non-invasive peripheral arterial tonometry in patients with Chronic Obstructive Pulmonary Disease compared with healthy subjects [Articolo su rivista]
Malerba, Mario; Radaeli, Alessandro; Nardin, N. . . .; Clini, Enrico; Carpagnano G., Elisiana; Sciatti, E. . . . .; Salghetti, F. . . .; Bonadei, I. . . . .; Platto, F. . . . .; Vizzardi, E. . . . . . .
abstract

available in the printed version

2018 - Evaluatuion of health-related quality of life in pulmonary diseases. [Articolo su rivista]
Polastri, M; Clini, E; Nava, S; Vitacca, M; Ambrosino, N.
abstract

Not available

2018 - Incidence, etiology and clinico-pathologic features of endobronchial benign lesions: 10 consecutive years rerospective study [Articolo su rivista]
Marchioni, Alessandro; Casalini, E; Andreani, A; Cappiello, G; Castaniere, Ivana; Fantini, R; Mengoli, C; Tonelli, Roberto; Clini, E; Rossi, G.
abstract

Introduction. Airways can be largely affected by non-neoplastic lesions including infectious and inflammatory diseases leading to critical stenosis of the lumen. The real-life incidence, etiology and clinical significance of endobronchial benign lesions are not systematically characterized. This study aimed at assessing the epidemiology of non-malignant processes involving the bronchial tree on clinical, pathologic, endoscopic and radiological grounds. Materials and methods. We retrospectively analyzed bronchoscopy procedures over 10 years (January 2005 to December 2014) at the Bronchoscopy Unit of the University Hospital of Modena. All the endoscopically-visible growing benign lesions with histological confirmation were considered, including casesassociated with critical stenosis of the lumen. For each lesion, we evaluated demographics, clinical features and outcome, endoscopic aspect, and radiological characteristic by means of Computed Tomography (CT) as assessed by two experienced radiologists blinded to the diagnosis. Results. Over the study period, we analyzed 10431 bronchoscopies and identified 2,075 cases of tracheobronchial alterations. Among these, 11.2% (n=232) had a benign etiology with an average annual incidence of 23 (range, 16-36) new cases/year and a general incidence of 2.2%. Among all the lesions, 81% (n=1691) was malignant, 7% (n=152) of unknown cause,38% (n=88) was inflammatory, 32% (n=74) infectious, 16% (n=36) were benign neoplasms,and 13% (n=31) iatrogenic diseases. Anthrachosis (36 cases, 15.5%) was the most prevalent bronchial lesion. Twenty-two% of benign lesions presented airway stenosis greater than 50% and required bronchoscopic treatment. The most frequent endobronchial diseases requiring medical treatment were endobronchial tuberculosis (14.2%), sarcoidosis (8.2%) and aspergillosis (10.8%). Bronchial stenosis was most frequently observed in tuberculosis (p=0.031) and aspergillosis (p=0.020) when compared to sarcoidosis. Immunosuppressive status was significantly associated with endobronchial aspergillosis (p=0.0001). Neither diagnosis of tuberculosis, sarcoidosis, and aspergillosis nor the immune system condition influenced one-year survival. Conclusion: A consistent proportion of endobronchial benign lesions is reported from the real-life bronchoscopic procedures. One-fifth of these are associated with critical stenosis of the airway lumen, requiring rigid bronchoscopy intervention. One-year survival was not significantly affected by the host immunity status.

2018 - LABA/LAMA fixed dose combinations in patients with COPD: a systematic review [Articolo su rivista]
Rogliani, P; Calzetta, L; Braido, F; Cazzola, M; Clini, E; Pelaia, G; Rossi, A; Scichilone, N; Di Marco, F.
abstract

Objectives: To assess the current evidence for long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) in the treatment of COPD. Methodology: A systematic literature search of randomized-controlled trials published in English up to September 2017 of LABA/LAMA FDCs versus LABA or LAMA or LABA/inhaled corticosteroid (ICS) FDCs in COPD patients was performed using PubMed, Embase, Scopus and Google Scholar. Outcomes including forced expiratory volume in 1 s (FEV1), Transition Dyspnea Index (TDI) scores, St. George's Respiratory Questionnaire (SGRQ) scores, exacerbations, exercise tolerance (ET), inspiratory capacity (IC) and rescue medication use were evaluated. Results: Twenty-seven studies were included in the review. LABA/LAMA FDCs significantly improved lung function (FEV1) at 12 weeks compared with LABA or LAMA or LABA/ICS. These effects were maintained over time. Significant improvements with LABA/LAMA FDCs versus each evaluated comparator were also observed in TDI and SGRQ scores, even if significant differences between different LABA/LAMA FDCs were detected. Only the LABA/LAMA FDC indacaterol/glycopyrronium has shown superiority versus LAMA and LABA/ICS for reducing exacerbation rates, while olodaterol/ tiotropium and indacaterol/glycopyrronium have been shown to improve ET and IC versus the active comparators. Rescue medication use was significantly reduced by LABA/LAMA FDCs versus the evaluated comparators. LABA/LAMA FDCs were safe, with no increase in the risk of adverse events with LABA/LAMA FDCs versus the monocomponents. Conclusions: Evidence supporting the efficacy of LABA/LAMA FDCs for COPD is heterogeneous, particularly for TDI and SGRQ scores, exacerbation rates, ET and IC. So far, indacaterol/glycopyrronium is the LABA/LAMA FDC that has the strongest evidence for superiority versus LABA, LAMA and LABA/ICS FDCs across the evaluated outcomes. LABA/LAMA FDCs were safe; however, more data should be collected in a real-world setting to confirm their safety.

2018 - Looking for a Chronic Care Model in COPD patients [Articolo su rivista]
Clini, Enrico; Castaniere, Ivana; Tonelli, Roberto
abstract

Not available

2018 - NIV in Chronic COPD. [Monografia/Trattato scientifico]
Clini, E; Ambrosino, N; Crisafulli, E; Vagheggini, G
abstract

Chronic Respiratory Failure (CRF) develops very frequently in the late stage of Chronic Obstructive Pulmonary Disease (COPD). At present, only long term oxygen-therapy (LTOT) is a recognised treatment able to significantly improve survival in chronically hypoxaemic COPD patients. Although long-term non invasive ventilation (NIV) is widely accepted for the treatment of chronic hypercapnia due to restrictive thoracic or neuromuscular diseases its use in stable hypercapnic COPD patients is still discussed. Four potential mechanisms explaining the effectiveness of NIV, as applied by positive pressure (NIV), in these patients rely to: 1) unloading respiratory muscles, 2) improvement of sleep quality and correction of hypoventilation, 3) “resetting” of respiratory centers, and 4) cardiovascular effects. In hypercapnic COPD, home NIV was associated to longer survival as compared with standard care when it was targeted to maximise reduction of hypercapnia, or in patients being discharged after acute on CRF. Despite the ability to improve gas exchange and health related quality of life, and to reduce readmissions, the generalized use of NIV in hypercapnic stable COPD still remain questionable. International documents provide indications for NIV prescription in COPD. Presence of nocturnal hypoventilation, sleep fragmentation and multiple acute exacerbations per/year are considered the optimal indication for home NIV in these patients, in particular when a progressive deterioration of clinical conditions and instability of the respiratory function are reported.

2018 - Pretreatment rate of decay in forced vital capacity predicts long-term response to pirfenidone in patients with idiopathic pulmonary fibrosis. [Articolo su rivista]
Biondini, D.; Balestro, E.; Lacedonia, D.; Cerri, S.; Milaneschi, R.; Luppi, F.; Cocconcelli, E.; Bazzan, E.; Clini, E.; Foschino, M. P.; Cosio, M. G.; Saetta, M.; Spagnolo, P.
abstract

Pirfenidone reduces functional decline and disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. In this study, we evaluated whether response to pirfenidone is influenced by the pre-treatment rate of forced vital capacity (FVC) decline. Fifty-seven IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or <10% predicted. Patients were followed-up every 6 months and up to 24 months following institution of pirfenidone treatment. In the entire population, pirfenidone reduced significantly the rate of FVC decline from 222 ml/yr to 68 ml/yr at 12 month (p<0.01) and 86 ml/yr at 24 month (p=0.04) follow-up. In RP, the reduction of FVC decline was evident at 6 months (706 ml/yr pre-treatment vs 35 ml/yr; p<0.01) and maintained, though to a lesser degree, at 12 (105 ml/yr; p< 0.01) and 24 months (125 ml/yr; p<0.02). Conversely, among SP the reduction in FVC decline was not significant at any of the time points analyzed. Pirfenidone reduces significantly the rate of FVC decline in patients with IPF. However, the beneficial effect is more pronounced and long-lasting in patients with rapidly progressive disease.

2018 - Pulmonary rehabilitation for patients with COPD during and after an exacerbation-related hospitalization: back to the future ? [Articolo su rivista]
Spruit, Martijn A.; Singh, Sally; Rochester, Carolyn; Greening, Neil; Franssen, Frits; Pitta, Fabio; Troosters, Thierry; Nolan, Claire; Vogiatzis, Ioannis; Clini, Enrico; Man, William; Burtin, Chris; Goldstein, Roger; Vanfleteren, Lowie; Kenn, Klaus; Nici, Linda; Janssen, Daisy; Casaburi, Richard; Shioya, Takanobu; Garvey, Chris; Carlin, Brian; Zuwallack, Richard; Steiner, Michael; Wouters, Emiel; Puhan, Milo
abstract

Not available

2018 - Tai Chi recreational exercise is not rehabilitation [Articolo su rivista]
Ambrosino, N; Polastri, M; Vitacca, M; Nava, S; Clini, E.
abstract

Not available

2018 - Textbook of Pulmonary Rehabilitation [Monografia/Trattato scientifico]
Clini, Enrico; Holland, Anne; Pitta, Fabio; Troosters, Thierry
abstract

This book provides up-to-date knowledge on all aspects of the multidisciplinary approach to pulmonary rehabilitation that is essential in order to achieve optimal results. It will be an ideal resource especially for pulmonologists in training, but will also be of value for physiotherapists, other health care professionals, and technicians. Detailed information is presented on the diverse program components in pulmonary rehabilitation, with clear explanation of the roles of the nutritionist, psychologist, occupational therapist, respiratory nurse, and physical activity coach. Guidance is provided on identification of candidates for pulmonary rehabilitation and on all aspects of assessment, including exercise capacity, muscle function, and physical activity. Patient-centered, economic, and other outcomes are examined, with separate discussion of combined outcome assessment. Furthermore, due consideration is given to organizational aspects of pulmonary rehabilitation and to rehabilitation in specific scenarios, e.g., thoracic oncology and surgery, transplantation, and the ICU. The authors are internationally recognized experts selected for their expertise in the topics they discuss.

2018 - The encaged lung: rapidly progressive idiopathic pleurisy. [Articolo su rivista]
Castaniere, I; Tonelli, R; Fantini, R; Marchioni, A; Garofalo, M; Clini, E; Cerri, S.
abstract

Here we present a case of an idiopathic fibrinous pleurisy affecting a 56-year old non-smoker male that has shown a rapidly progressive course. With a brief review of the literature we discuss the absence of any identified cause of pleurisy as a relatively common condition, requiring attention and clinical awareness.

2018 - Ultrasound assessed Diaphragm Impairment is a Predictor of Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease undergoing Non-Invasive Ventilation. [Articolo su rivista]
Marchioni, Alessandro; Castaniere, Ivana; Tonelli, Roberto; Fantini, Riccardo; Fontana, Matteo; Luca, Tabbi; Andrea, Viani; Francesco, Giaroni; Ruggieri, Valentina; Cerri, Stefania; Clini, Enrico
abstract

Background. Ultrasound (US) evaluation of diaphragm dysfunction (DD) has proved to be a reliable technique in critical care. In this single center prospective study we investigated the impact of US assessed DD on Non Invasive Ventilation (NIV) failure in AECOPD patients and its correlation with the trans-diaphragmatic pressure assessed through invasive sniff maneuver (Pdi sniff). Methods. A population of 75 consecutive AECOPD with hypercapnic acidosis admitted in our Respiratory Intensive Care Unit (RICU) were enrolled. Change of the diaphragm thickness (ΔTdi) < 20% during tidal volume was the pre-definite cut off to identify DD+/-. Correlations between ΔTdi <20% NIV failure and other clinical outcomes was investigated. Correlation between ΔTdi and Pdi sniff values was analyzed in a subset of 10 patients. Results. DD+ had higher risk for NIV failure as compared with DD- (RR= 4.4, p<0.001) and was significantly associated with greater RICU, in-hospital and 90-day mortality rate, MV duration, tracheostomy rate, and RICU stay. A huge increase in NIV failure (HR=6.2, p< 0.0001) and 90-day mortality (HR=4.7, p=0.008) in DD+ was reported at the Kaplan-Meyer analysis. ΔTdi highly correlated with Pdi sniff (r Pearson = 0.81, p= 0.004). ΔTdi< 20% showed better accuracy in predicting NIV failure when compared to baseline pH value and early change of both arterial blood pH and pCO2 following NIV start (AUC=0.84, 0.51, 0.56, 0.54 respectively, p<0.0001). Conclusion. Early and non-invasive US assessment of DD during severe AECOPD is reliable and accurate in identifying patients at major risk for NIV failure and worse prognosis.

2018 - Use of adjunctive cardiovascular therapy in patients hospitalized for acute exacerbations of COPD. [Articolo su rivista]
Roversi, S; Tonelli, R; Beghè, Bianca; Banchelli, F; D’Amico, Roberto; Malerba, Mario; Fabbri, Lm; Clini, E.
abstract

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is one of the most frequent diagnoses in patients presenting with acute dyspnea or respiratory failure. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document, it is defined clinically, as acute worsening of respiratory symptoms that result in additional therapies, being bronchodilators, corticosteroids, and antibiotics the cornerstone of acute management. However, comorbidities in COPD, including cardiac disease, contribute significantly to heterogeneity of the single acute episode in real-life practice. Therefore, we were interested in evaluating how patients admitted to the hospital with a clinical diagnosis of AECOPD were managed at admission, and we analyzed the therapeutic approach at onset of AECOPD in hospitalized patients, aiming at assessing the adjunctive use of diuretic therapy.

2018 - Vanishing lung emphysema during chemotherapy for malignant pleural mesothelioma. [Articolo su rivista]
Castaniere, I; Tonelli, R; Taddei, S; Taschini, S; Fantini, R; Marchioni, A; Covi, M; Clini, E.
abstract

We report the case of a 79-year-old man with a tobacco smoke-related left dystrophic bullous emphysema that showed a considerable recovery of the cystic abnormalities during chemotherapy for pleural malignant mesothelioma. We suggest that the disappearance of the dystrophic emphysema could be explained by the combined effect of chemotherapy and pleural disease. We briefly review the literature and we discuss the possible mechanism of this unforeseen manifestation.

2017 - An uncommon cause of pneumonia: The golden diagnosis [Articolo su rivista]
Fabbri, Laura; Tonelli, Roberto; Andreani, Alessandro; Castaniere, Ivana; Fantini, Riccardo; Marchioni, Alessandro; Clini, Enrico
abstract

A 28-year-old sub-Saharan African Italian non-smoker male presented with signs and symptoms of pneumonia and respiratory failure. Despite antibiotic treatment he experienced a significant worsening of respiratory conditions and admission to intensive care unit. He thus underwent chest computed tomography followed by fiberopict bronchoscopy with bronchoalveolar lavage whose macroscopic examination led to the diagnosis of acute chest syndrome. A brief literature review was conducted to discuss the first manifestation of this disease.

2017 - COPD exacerbation and diaphragmatic dysfunction: Conditions with mutual influence influencing outcomes? - Reply. [Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Antenora, Federico; Fantini, Riccardo; Clini, Enrico
abstract

Not available

2017 - Chronic respiratory abnormalities in the multi-morbid frail elderly [Articolo su rivista]
Beghe', Bianca; Clini, Enrico; Fabbri, L. M.
abstract

Two-thirds of people aged ≥ 65 years have multi-morbidity, with people living in the most deprived areas developing multi-morbidity 10-15 years even earlier. Multi-morbidity is associated with higher mortality, polypharmacy and high treatment burden, higher rates of adverse drug events, and much greater health services use including emergency hospital admissions. Multi-morbidity includes both physical and mental health conditions, as anxiety and depression, that almost invariably affect patients with multiple symptomatic chronic diseases. The main message of the present paper is that the management of a patient with any of the chronic diseases that are part of multi-morbidity is not just the management of that single index disease, but must include the active search and proper treatment of concomitant chronic diseases. The presence of concomitant chronic diseases should not alter the management of the index disease (eg COPD), and concomitant chronic disease should be treated according to single diseases guidelines regardless of the presence of the index disease, obviously with careful consideration that this choice implies complex management, polypharmacy and potential adverse effects. Ongoing multidisciplinary hospital and home base management programmes suggest that an olistic integrated approach might improve quality of life and reduce hospital admissions and death in these multimorbid patients.

2017 - Effectiveness of pulmonary rehabilitation in patients with INTERSTITIAL LUNG DISEASE of different etiology: a multicenter prospective study [Articolo su rivista]
Tonelli, Roberto; Cocconcelli, Elisabetta; Lanini, Barbara; Romagnoli, Isabella; Florini, Fabio; Castaniere, Ivana; Andrisani, Dario; Cerri, Stefania; Luppi, Fabrizio; Fantini, Riccardo; Beghe', Bianca; Marchioni, Alessandro; Gigliotti, Francesco; Clini, Enrico
abstract

Recent evidences show that Pulmonary Rehabilitation (PR) is effective in patients with Interstitial Lung Disease (ILD). Uncertainty still remains on how disease severity and/or etiology might impact on benefits. We designed this prospective study 1) to confirm the efficacy of rehabilitation in a population of patients with ILDs and 2) to investigate whether baseline exercise capacity, disease severity or ILD etiology might affect outcomes . Forty-one patients (IPF 63%, age 66.9 ± 11 ys) were enrolled in a standard PR course in two centers. Lung function, incremental and endurance cyclo-ergometry, Six Minutes Walking Distance (6MWD), chronic dyspnea (Medical Research Council scale-MRC) and quality of life (St. George Respiratory Questionnaire-SGRQ) were recorded before and at the end of PR to measure any pre-to-post change. Correlation coefficients between the baseline level of Diffuse Lung Capacity for Carbon monoxide (DLCO), Forced Vital Capacity (FVC), 6MWD, power developed during incremental endurance test, GAP index (in IPF patients only) and etiology (IPF or non-IPF) with the functional improvement of and HRQoL were assessed. Out of the 41 patients, 97% (n=40) completed the PR course. Exercise performance (both at peak load and submaximal effort), symptoms (iso-time dyspnea and leg fatigue), SGRQ and MRC significantly improved after PR (p < .001). Patients with lower baseline 6MWD showed greater improvement in 6MWD (Spearman r score = - .359, p = .034) and symptoms relief at SGRQ (r = -.315, p = .025) regardless of underlying disease. Present study confirms that comprehensive rehabilitation is feasible and effective in patients with ILD of different severity and etiology. The baseline submaximal exercise capacity inversely correlates with both functional and symptom gains in this heterogeneous population.

2017 - GOLD 2017 recommendations for COPD patients: toward a more personalized approach [Articolo su rivista]
Roversi, Sara; Corbetta, Lorenzo; Clini, Enrico
abstract

The Global Initiative for Chronic Obstructive Lung Disease (GOLD), an international committee of experts, has recently published its updated report on diagnosis and management of Chronic Obstructive Pulmonary Disease (COPD). Compared to the previous version, this documents has been an extensively revised: the definition has been simplified, highlighting the importance of respiratory symptoms, and disease development is further discussed, including new insights on lung development. Spirometry is still required for the diagnosis, and it is described as fundamental tool for evaluating prognosis, disease progression, and non-pharmacologic treatment. However, differently from the previous version, spirometry is no longer included in the ABCD tool (ie, a practical tool proposed to assess COPD symptom burden and guide pharmacologic treatment), which is now centered exclusively on respiratory symptoms and history of exacerbation. Subsequently, pharmacologic treatment has been shifted towards a more personalized approach, reflecting the ongoing process toward a comprehensive, patient-tailored management

2017 - Integrating the care of the complex COPD patient [Articolo su rivista]
Donner, Claudio; Carrozzi, Laura; Maio, Sara; Baldacci, Sandra; Pistelli, Francesco; Viegi, Giovanni; Purro, Andrea; Torchio, Roberto; Clini, Enrico; Amaducci, Sandro; Goldstein, Roger; Morgan, Mike; Bourbeau, Jean; Vagheggini, Guido; Wouters, Emiel FM; Zuwallack, Richard L.
abstract

The European Seminars in Respiratory Medicine has represented an outstanding series updating new science in respiratory disease from the 1990’s up to the early beginning of this 21st century [1,2]. Its aim is to update issues and current science, focusing on the multidisciplinary approach to patients with respiratory disease. As such, it represents a unique opportunity for specialists in Respiratory Medicine involved in Basic and Clinical Research to discuss topical and debated problems in medical care, at a top level forum guided by an expert panel of authors. The structure of the seminar is based on the following pillars: • Attendance at the Seminars is strictly limited: selection of participants is based, in order of priority, on scientific curriculum, age (younger specialists are privileged), and early receipt of the application form. • Each topic is allotted considerable time for presentation and discussion. The first section is devoted to a series of presentations (with adequate time allocated for discussion) by an expert panel of researchers and clinicians. In the second section involves discussions of controversial issues, in a smaller audience format encouraging interaction between the panel and audience. • “Meet the expert” seminars discuss topical subjects in more depth, utilizing an interactive tutorial.

2017 - Manuale di Pneumologia [Monografia/Trattato scientifico]
Clini, Enrico; Pelaia, Girolamo
abstract

Il manuale rappresenta un trattato di medicina specialistica in ambito pneumologico che aggiorna le più attuali conoscenze. Ad esso hanno contribuito numerosi autori e docenti delel più prestigiose sedi accademiche e ospedaliere del nostro paese.

2017 - Pneumologia [Capitolo/Saggio]
Clini, Enrico; Beghe', Bianca; Cerri, Stefania; Fabbri, L. E. O. N. A. R. D. O.
abstract

Non disponibile

2017 - Prevalence and outcome of diaphragmatic dysfunction assessed by ultrasound technology during acute exacerbation of chronic obstructive pulmonary disease: a pilot study. [Articolo su rivista]
Antenora, F; Fantini, R; Iattoni, A; Livrieri, Francesco; Castaniere, Ivana; Sdanganelli, Antonia; Tonelli, Roberto; Zona, Stefano; Clini, Enrico; Marchioni, A.
abstract

Background. The prevalence and clinical consequences of diaphragmatic dysfunction (DD) during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are still not known. The aim of this study was a) to evaluate the prevalence of DD as assessed by ultrasonography, b) to report the impact of DD on non-invasive ventilation (NIV) failure, length of hospital stay, and short and long-term mortality in severe AECOPD patients admitted to intensive care. Method. Forty one consecutive patients with AECOPD and respiratory acidosis admitted over a 12 month period to the respiratory Intensive Care Unit (ICU) of the University Hospital of Modena were studied. Diaphragmatic ultrasound was performed on admission before starting NIV. A change of diaphragm thickness (ΔTdi) less than 20% during spontaneous breathing was considered to confirm the presence of dysfunction (DD+). NIV failure and other clinical outcomes (duration of MV, tracheostomy, length of hospital stay and mortality ) were also recorded. Results. Ten out of 41 patients (24.3%) presented DD+, which was significantly associated with steroid use (p=0.002, R-squared=0.19). DD+ was found to correlate with NIV failure (p&lt;0.001, R-squared=0.27), longer ICU stay (p=0.02, R-squared=0.13), prolonged mechanical ventilation (p=0.023, R-squared=0.15) and need for tracheostomy (p=0.006, R-squared=0.20). Moreover, the Kaplan-Meyer survival estimates showed that NIV failure (log-rank=0.001) and mortality in respiratory ICU (log-rank=0.039) were significantly associated with DD+. Conclusions. In AECOPD patients hospitalised and submitted to NIV, severe dysfunction of the diaphragm was seen in almost a quarter of patients. Dysfunction of the diaphragm may cause NIV failure, and impact on the use of clinical resources and on the patient’s short-term mortality.

2017 - The potential role of endothelial dysfunction and platelet activation in the development of thrombotic risk in COPD patients [Articolo su rivista]
Malerba, ; M:, Nardin; M:, Radaeli; A, ; Montuschi, P; Carpagnano, G; Clini, Enrico
abstract

Introduction: Despite lack of knowledge in the field, several studies have underlined the role of endothelium dysfunction and platelet activation as significant players in the development and progression of chronic obstructive pulmonary disease (COPD). Indeed, endothelium plays a crucial role in vascular homeostasis and impairment, due to the inflammation process enhanced by smoking. Chronic inflammation and endothelial dysfunction have been proved to drive platelet activity. Consequently, thrombotic risk is enhanced in COPD, and might explain the higher percentage of cardiovascular death in such patients. Areas covered: This review aims to clarify the role of endothelium function and platelet hyper-activity as the pathophysiological mechanisms of the increased thrombotic risk in COPD. Expert commentary: In COPD patients, chronic inflammation does not impact only on lung parenchyma, but potentially involves all systems, including the endothelium of blood vessels. Impaired endothelium has several consequences, such as reduced vasodilatation capacity, enhanced blood coagulation, and increased platelet activation resulting in higher risk of thrombosis in COPD patients. Endothelium dysfunction and platelet activation are potential targets of therapy in patients with COPD aiming to reduce their risk of cardiovascular events.

2016 - Etiology and Level of Lung Derangement Do Not Affect the Beneficial Effect of Pulmonary Rehabilitation in Patients with Interstitial Lung Diseases [Abstract in Rivista]
Tonelli, Roberto; Lanini, Barbara; Romagnoli, Isabella; Presi, Ilenia; Cocconcelli, Elisabetta; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Gigliotti, Francesco; Clini, Enrico
abstract

A growing body of literature suggests that comprehensive Pulmonary Rehabilitation (PR) improves symptoms and functional capacity also in patients with Interstitial Lung Disease. Aim of this study was to investigate whether the baseline level of functional capacity or lung derangement, and ILD etiology may predict and affect outcomes’ response to PR in these patients. MATERIALS AND METHODS Patients with ILD of different etiology were referred and prospectively admitted to PR, delivered according to a standardized protocol. Spirometry, Diffuse Lung Capacity for Carbon Monoxide [DLCO], incremental cyclo-ergometry test, Six Minutes Walking Distance Test [6MWDT], questionnaires on dyspnea and quality of life (St. George Respiratory Questionnaire-SGRQ, 5-point Medical Research Council scale-MRC) were assessed pre- and post- rehabilitation course; change from baseline of any measured variables was considered to assess the impact of PR on functional capacity, perceived symptoms and quality of life, respectively. Patients were stratified according to their level of DLCO, Forced Vital Capacity (FVC), 6MWTD, etiology (IPF or non-IPF), and GAP index (in IPF patients only). Analyses of changes from baseline and correlation test were conducted as appropriate. RESULTS Thirty-nine patients (mean age 66.87 ± 10.9 ys, IPF 62.5%) were enrolled and completed the PR course. 6MWDT (+54.3m, 95%CI 34.9-73.7, p < .0001), cycling time (+ 70.0%, p = .0009) and power (+60.4%, p= .008), iso-time dyspnea (-33.1%, p < .0001) and limb fatigue (-40.8%, p < .0001), SGRQ, MRC (p < .0001) significantly improved over time. Patients with lower baseline 6MWD showed greater change in 6MWD (Pearson r score = - .359, p = .034) and symptoms relief at SGRQ (r = -.229, p = .038). Different levels of FVC, DLCO, GAP index and etiology did not correlate with functional and symptoms outcomes. CONCLUSION Present study confirms that comprehensive rehabilitation is effective in patients with ILDs of different severity, and etiology and that baseline walking capacity inversely correlates with functional and symptom changes. Lung derangement or etiology does not affect outcomes following rehabilitation.

2016 - Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers [Articolo su rivista]
Santini, G.; Mores, N.; Shohreh, R.; Valente, S.; Dabrowska, M.; Trové, A.; Zini, G.; Cattani, P.; Fuso, L.; Mautone, A.; Mondino, C.; Pagliari, G.; Sala, A.; Folco, G.; Aiello, M.; Pisi, R.; Chetta, A.; Losi, M.; Clini, Enrico; Ciabattoni, G.; Montuschi, P.
abstract

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P  <  0.02; healthy subjects: P  <  0.03), whereas EBC PGE2 was elevated in current (P  =  0.0065) and ex-smokers with COPD (P  =  0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P  <  0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P  <  0.01; healthy subjects: P  <  0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P  =  0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

2016 - Increasing Implementation and Delivery of Pulmonary Rehabilitation: Key Messages from the New ATS/ERS Policy Statement. [Articolo su rivista]
Vogiatzis, I; Rochester, Cl; Spruit, Ma; Thierry Troosters, T; Clini, Enrico; on behalf of the American Thoracic Society/European Respiratory Society Task Force on Policy in Pulmonary, Rehabilitation
abstract

In December 2015 the Official ATS/ERS Policy Statement on Enhancing Implementation, Use and Delivery of Pulmonary Rehabilitation (PR) was published [1] with the aim of providing policy recommendations to increase implementation and delivery of PR worldwide. Major areas addressed included increasing healthcare professional, payer and patient awareness and knowledge of PR, increasing patient access to PR, improving quality of PR programs and future research directions to advance evidence-based policy in PR. This ATS/ERS document was developed via an iterative consensus process by an ad hoc Task Force on Policy in PR comprised of experts from the ATS Pulmonary Rehabilitation Assembly, the ERS Rehabilitation and Chronic Care Group, the ATS and ERS Documents Development and Implementation Committees, representatives from the European Lung Foundation (ELF) and primary care representatives from the USA and Europe between May 2013 and January 2015. Input was obtained via informal surveys from patients, patient advocacy groups, (including the ATS Public Advisory Roundtable and ELF), insurance payers, as well as primary and pulmonary specialty healthcare providers. The Policy Statement was approved by the Board of Directors of the ATS and the Science Council and Executive Committee of the ERS. This editorial provides ERJ readers with a concise reflection on the key issues addressed and summarizes the policy recommendations made in the ATS/ERS Policy Statement[1] to enhance implementation, use and delivery of PR.

2016 - Organization of a weaning Unit [Capitolo/Saggio]
Clini, Enrico; Montanari, G; Ciobanu, L; Vitacca, M.
abstract

Weaning from mechanical ventilation (MV) is an essential and universal element in the care of critically ill patients receiving MV for a prolonged time to restore unassisted breathing. There is much evidence that weaning tends to be delayed, exposing the patient to unnecessary discomfort, increased risk of complications, and increased cost of care. In the past 15 years, availability of beds in intensive care units (ICUs) and new technologies, such as noninvasive mechanical ventilation, coupled with improved levels of care, have highlighted a new population of patients labeled as survivors of a catastrophic illness. Although this group of patients represents less than 10 % of all ICU admissions, they account for a disproportionate burden on health-care financial resources. In most studies, weaning failure occurs when a spontaneous breathing trial (SBT) fails and reintubation is needed [1]. Failure of an SBT is defined by (1) objective indices of failure, such as tachypnea, tachycardia, ypertension, hypotension, hypoxemia or acidosis, and arrhythmia, and (2) subjective indices, such as agitation or distress, depressed mental status, diaphoresis, and evidence of increasing effort. Several studies have proposed the use of noninvasive ventilation (NIV) for extubated patients in different clinical situations, including prophylactic intervention in patients with chronic obstructive pulmonary disease who failed SBT [2], patients with repeated SBT failure [3], and postsurgical patients.

2016 - Platelet activation and cardiovascular co-morbidities in patients with chronic obstructive pulmonary disease. [Articolo su rivista]
Malerba, M; Olivini, A; Radaeli, A; Ricciardolo, F; Clini, Enrico
abstract

Objective: Platelet activation in COPD patients is associated with an increased risk of cardiovascular events. Aim of the study: to assess the mean platelet volume (MPV), as an index of platelet activation, in patients with COPD both when stable or during exacerbation. Research design and methods: 478 patients with COPD (75 with exacerbation) and 72 age-matched healthy controls were enrolled. Medical history, co-morbidities, medications, pulmonary function tests, MPV and blood cell count, erythrocyte sedimentation rate (ERS) and C reactive protein (CRP) were recorded. Results: MPV was higher in COPD patients than in controls (8.7 ± 1.1 fL and 8.4 ± 0.8 fL respectively, p = 0.025) and increased across the severity of the diseases as assessed by the GOLD post bronchodilator FEV1 categorized I to IV (p>0.05). MPV was higher in COPD patients during acute exacerbation as compared with stable condition (8.7 ± 1.0 fL and 8.9 ± 1.0 fL, p = 0.021). MPV ≥ 10.5 fL correlated with the presence of at least one co-existing cardiovascular disease (p = 0.008) . No correlation was observed between MPV and CRP or ERS in patients or in controls. An inverse significant correlation was found between platelets count and MPV in COPD patients. Conclusions: Elevated MPV is associated with lower platelet count and with cardiovascular co-morbidity in COPD patients. MPV value is higher in more severe COPD and during acute exacerbation. Present findings warrant future studies to confirm a possible clinically relevant role for platelet activation and cardiovascular risk in the population of COPD.

2016 - Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis. [Articolo su rivista]
Fantini, R; Mandrioli, J; Zona, S; Antenora, F; Iattoni, A; Monelli, M; Fini, N; Tonelli, Roberto; Clini, Enrico; Marchioni, A.
abstract

Background: Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (Tdi) with a new parameter (Tmax index). Methods: 41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or TLC, and their ratio (Tmax) were recorded. Changes (Δ) in Tdi indices during tidal volume (TdiVt) and maximal inspiration (TdiTLC) were also assessed. Results: TdiTLC (p &lt;0.001) and Tmax (p= 0.007), but not TdiVt, differed between patients and controls. Significant correlation (p&lt;0.05) was found between TdiTLC, Tmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Δtmax than with ΔtdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25). Conclusions: Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. Tmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests.

2016 - What is the origin of dyspnoea in smokers without airway disease ? [Articolo su rivista]
Clini, Enrico; Beghe', Bianca; Fabbri, Leonardo
abstract

Not available

2015 - 8th International conference on management and rehabilitation of chronic respiratory failure: the long summaries – Part 3 [Articolo su rivista]
Ambrosino, N.; Casaburi, R.; Chetta, A.; Clini, Enrico; Donner, C. F.; Dreher, M.; Goldstein, R.; Jubran, A.; Nici, L.; Owen, C. A.; Rochester, C.; Tobin, M. J.; Vagheggini, G.; Vitacca, M.; Zuwallack, R.
abstract

This paper summarizes the Part 3 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 3) presents a section regarding Moving Across the Spectrum of Care for Long-Term Ventilation (Moving Across the Spectrum of Care for Long-Term Ventilation, New Indications for Non-Invasive Ventilation, Elective Ventilation in Respiratory Failure - Can you Prevent ICU Care in Patients with COPD?, Weaning in Long-Term Acute Care Hospitals in the United States, The Difficult-to-Wean Patient: Comprehensive management, Telemonitoring in Ventilator-Dependent Patients, Ethics and Palliative Care in Critically-Ill Respiratory Patients, and Ethics and Palliative Care in Ventilator-Dependent Patients).

2015 - 8th International conference on management and rehabilitation of chronic respiratory failure: the long summaries – part 2 [Articolo su rivista]
Ambrosino, N.; Casaburi, R.; Chetta, A.; Clini, Enrico; Donner, C. F.; Dreher, M.; Goldstein, R.; Jubran, A.; Nici, L.; Owen, C. A.; Rochester, C.; Tobin, M. J.; Vagheggini, G.; Vitacca, M.; Zuwallack, R.
abstract

This paper summarizes the Part 2 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 2) includes sections regarding: Promoting Physical Activity across the Spectrum of COPD (Physical activity: definitions, measurements, and significance; Increasing Physical Activity through Pharmacotherapy in COPD); Pulmonary Rehabilitation in Critical Illness (Complex COPD with comorbidities and its impact during acute exacerbation; Collaborative Self-Management in COPD: A Double-Edged Sword?; and Pulmonary Rehabilitation in Critical Illness.

2015 - 8th international conference on management and rehabilitation of chronic respiratory failure: the long summaries – part 1 [Articolo su rivista]
Ambrosino, N.; Casaburi, R.; Chetta, A.; Clini, Enrico; Donner, C. F.; Dreher, M.; Goldstein, R.; Jubran, A.; Nici, L.; Owen, C. A.; Rochester, C.; Tobin, M. J.; Vagheggini, G; Vitacca, M.; Zuwallack, R.
abstract

This paper summarizes the Part 1 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 1) includes sections regarding: Advances in Asthma and COPD Therapy (Novel Therapeutic Targets for Asthma: Proteinases, Blood Biomarker Changes in COPD Patients); The problem of Hospital Re-Admission following Discharge after the COPD Exacerbation (Characteristics of the Hospitalized COPD Patient, Reducing Hospital Readmissions Following COPD Exacerbation).

2015 - A Prospective Multicentric Study of Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease and Different Clinical Phenotypes [Articolo su rivista]
Ambrosino, N.; Venturelli, E.; De Blasio, F.; Paggiaro, P.; Pasqua, F.; Vitacca, M.; Vagheggini, G.; Clini, Enrico
abstract

Background. Recently it has been proposed that different clinical phenotypes can be recognised in COPD patients, namely predominant airway disease or parenchymal destructive changes. Objectives. The aim of this prospective multicentric study was to evaluate whether these two phenotypes may influence outcomes following a pulmonary rehabilitation program (PRP). Methods. We have prospectively evaluated 364 consecutive COPD (70±8 years, 76.3% males) admitted to a standard hospital-based PRP in 6 Italian centres and divided according to their phenotype into airway obstructive (Group 1, n=208) or parenchimal destructive (Group 2, n=156). Pre-to-post PRP values of six-minute walking distance, perceived breathlessness score (Medical Research Council), health related quality of life (St.George’s Respiratory Questionnaire), and respiratory muscle function (maximal inspiratory and expiratory pressure) were recorded. Results. PRP resulted in significant improvements in all outcome measures without any significant differences between groups. Conclusions. Our study confirms that COPD patients may benefit from pulmonary rehabilitation independent on their clinical phenotype.

2015 - Advances in Ambulatory Oxygen workshop and Longterm Oxygen therapy in real-life practice. [Articolo su rivista]
Clini, Enrico; Veale, D.; Winck, J. C.; Muir, J. F.; Kampelmacher, M.; Vivodtzev, I.; Little, S.
abstract

The practical workshop presented recent advances in the field of ambulatory oxygen (AO), with experts discussing identification of patients who would benefit from AO, as well as current trials to measure specific benefits of AO in chronic patients. In particular, AO prescription in clinical practice and developments in pulsed-dose delivery of AO as a more efficient method of oxygen delivery were extensively discussed. After audience questions, the attendees had the opportunity to handle the AO systems on display in order to gain greater insight into their functionality and wearability, which should assist them in providing the most appropriate device for each patient. The symposium addressed considerations required when prescribing long-term oxygen therapy (LTOT). Dr Kampelmacher reviewed current indications for LTOT, emphasising the importance of accurate assessment of patients for LTOT, optimisation of oxygen dose, and patient education. Dr Vivodtzev discussed the evidence for LTOT in patients with exercise-induced desaturation, the role of portable oxygen concentrators, and the optimisation necessary to benefit from their use. The symposium concluded with a health economic study presented by Dr Little, demonstrating the cost benefits of a reform of the Scottish healthcare oxygen supply service.

2015 - An official American Thoracic Society/European Respiratory Society policy statement: Enhancing implementation, use, and delivery of pulmonary rehabilitation [Articolo su rivista]
Rochester, C. L.; Vogiatzis, I.; Holland, A. E.; Lareau, S. C.; Marciniuk, D. D.; Puhan, M. A.; Spruit, M. A.; Masefield, S.; Casaburi, R.; Clini, Enrico; Crouch, R.; Garcia Aymerich, J.; Garvey, C.; Goldstein, R. S.; Hill, K.; Morgan, M.; Nici, L.; Pitta, F.; Ries, A. L.; Singh, S. J.; Troosters, T.; Wijkstra, P.; Yawn, B. P.; Zuwallack, R. L.
abstract

Rationale: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom-reducing, psychosocial, and health economic benefits for patients with chronic respiratory diseases, yet it is underutilized worldwide. Insufficient funding, resources, and reimbursement; lack of healthcare professional, payer, and patient awareness and knowledge; and additional patient-related barriers all contribute to the gap between theknowledge of the science andbenefits of PR and the actual delivery of PR services to suitable patients. Methods: Members of the American Thoracic Society (ATS) Pulmonary Rehabilitation Assembly and the European Respiratory Society (ERS) Rehabilitation and Chronic Care Group established a Task Force and writing committee to develop a policy statement on PR. The document was modified based on feedback from expert peer reviewers. After cycles of review and revisions, the statement was reviewed and formally approved by the Board of Directors of the ATS and the Science Council and Executive Committee of the ERS. Main Results: This document articulates policy recommendations for advancing healthcare professional, payer, and patient awareness and knowledge of PR, increasing patient access to PR, and ensuring quality of PR programs. It also recommends areas of future research to establish evidence to support the development of an updated funding and reimbursement policy regarding PR. Conclusions: The ATS and ERS commit to undertake actions that will improve access to and delivery of PR services for suitable patients. They call on their members and other health professional societies, payers, patients, and patient advocacy groups to join in this commitment.

2015 - An official American Thoracic Society/European Respiratory Society statement: research questions in COPD [Articolo su rivista]
Celli, B. R.; Decramer, M.; Wedzicha, J. A.; Wilson, K. C.; Agustí, A.; Criner, G. J.; Macnee, W.; Make, B. J.; Rennard, S. I.; Stockley, R. A.; Vogelmeier, C.; Anzueto, A.; Au, D. H.; Barnes, P. J.; Burgel, P. R.; Calverley, P. M.; Casanova, C.; Clini, Enrico; Cooper, C. B.; Coxson, H. O.; Dusser, D. J.; Fabbri, L. M.; Fahy, B.; Ferguson, G. T.; Fisher, A.; Fletcher, M. J.; Hayot, M.; Hurst, J. R.; Jones, P. W.; Mahler, D. A.; Maltais, F.; Mannino, D. M.; Martinez, F. J.; Miravitlles, M.; Meek, P. M.; Papi, A.; Rabe, K. F.; Roche, N.; Sciurba, F. C.; Sethi, S.; Siafakas, N.; Sin, D. D.; Soriano, J. B.; Stoller, J. K.; Tashkin, D. P.; Troosters, T.; Verleden, G. M.; Verschakelen, J.; Vestbo, J.; Walsh, J. W.; Washko, G. R.; Wise, R. A.; Wouters, E. F. M.; Zuwallack, R. L.
abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes.

2015 - An official American Thoracic Society/European Respiratory Society statement: research questions in chronic obstructive pulmonary disease [Articolo su rivista]
Celli, Bartolome R; Decramer, Marc; Wedzicha, Jadwiga A.; Wilson, Kevin C.; Agustí, Alvar; Criner, Gerard J.; Macnee, William; Make, Barry J.; Rennard, Stephen I.; Stockley, Robert A.; Vogelmeier, Claus; Anzueto, Antonio; Au, David H.; Barnes, Peter J.; Burgel, Pierre Regis; Calverley, Peter M.; Casanova, Ciro; Clini, Enrico; Cooper, Christopher B.; Coxson, Harvey O.; Dusser, Daniel J.; Fabbri, Leonardo; Fahy, Bonnie; Ferguson, Gary T.; Fisher, Andrew; Fletcher, Monica J.; Hayot, Maurice; Hurst, John R.; Jones, Paul W.; Mahler, Donald A.; Maltais, François; Mannino, David M.; Martinez, Fernando J.; Miravitlles, Marc; Meek, Paula M.; Papi, Alberto; Rabe, Klaus F.; Roche, Nicolas; Sciurba, Frank C.; Sethi, Sanjay; Siafakas, Nikos; Sin, Don D.; Soriano, Joan B.; Stoller, James K.; Tashkin, Donald P.; Troosters, Thierry; Verleden, Geert M.; Verschakelen, Johny; Vestbo, Jorgen; Walsh, John W.; Washko, George R.; Wise, Robert A.; Wouters, Emiel F. M.; Zuwallack, Richard L.
abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. METHODS: Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified. RESULTS: Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. CONCLUSIONS: Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.

2015 - An official American thoracic society/ European respiratory society statement: Research questions in COPD [Articolo su rivista]
Celli, B. R.; Decramer, M.; Wedzicha, J. A.; Wilson, K. C.; Agusti, A. A.; Criner, G. J.; MacNee, W.; Make, B. J.; Rennard, S. I.; Stockley, R. A.; Vogelmeier, C.; Anzueto, A.; Au, D. H.; Barnes, P. J.; Burgel, P. -R.; Calverley, P. M.; Casanova, C.; Clini, E. M.; Cooper, C. B.; Coxson, H. O.; Dusser, D. J.; Fabbri, L. M.; Fahy, B.; Ferguson, G. T.; Fisher, A.; Fletcher, M. J.; Hayot, M.; Hurst, J. R.; Jones, P. W.; Mahler, D. A.; Maltais, F.; Mannino, D. M.; Martinez, F. J.; Miravitlles, M.; Meek, P. M.; Papi, A.; Rabe, K. F.; Roche, N.; Sciurba, F. C.; Sethi, S.; Siafakas, N.; Sin, D. D.; Soriano, J. B.; Stoller, J. K.; Tashkin, D. P.; Troosters, T.; Verleden, G. M.; Verschakelen, J.; Vestbo, J.; Walsh, J. W.; Washko, G. R.; Wise, R. A.; Wouters, E. F. M.; ZuWallack, R. L.
abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes.

2015 - Chronic critical illness: the price of survival [Articolo su rivista]
Marchioni, A.; Fantini, Riccardo; Antenora, F.; Clini, Enrico; Fabbri, Leonardo
abstract

BACKGROUND: The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients. MATERIALS &amp; METHODS: No absolute definition of the disease is currently available, although most patients are characterized by the need for prolonged mechanical ventilation. Mortality rates are still high even after dismissal from intensive care unit (ICU) and transfer to specialized rehabilitation care settings. RESULTS: In recent years, some studies have tried to clarify the pathophysiological characteristics underlying chronic critical illness (CCI), a disease that is also characterized by severe endocrine and inflammatory impairments, partly accounting for the almost constant set of symptoms. DISCUSSION: Currently, no specific treatment is available. However, a strategic early therapeutic approach on ICU admission might try to prevent the progress of the acute disease towards chronic critical illness.

2015 - Clinical highlights: messages from Munich [Articolo su rivista]
Vogiatzis, I.; Marvisi, M.; Coolen, J.; Gasparini, S.; Antoniou, K.; Stallberg, B.; Herth, F.; Clini, Enrico
abstract

This article reviews a selection of presentations in the area of clinical problems that were presented at the 2014 European Respiratory Society International Congress in Munich, Germany. We review the most recent and relevant topics of interest in the area of clinical respiratory medicine, encompassing novel reports and studies that are of particular interest to healthcare professionals. Topics ranging from basic science to translation research are presented and discussed in the context of the most up-to-date literature. In particular, the reviewed topics deal with chronic obstructive pulmonary disease and asthma, idiopathic pulmonary fibrosis (pathogenesis and therapy), advances in functional chest imaging, interventional pulmonology, pulmonary rehabilitation, and chronic care.

2015 - Development of a syllabus for postgraduate respiratory physiotherapy education: the Respiratory Physiotherapy HERMES project [Articolo su rivista]
Troosters, T.; Pitta, F.; Oberwaldner, B.; Lewko, A.; Inal Ince, D.; Grant, K.; Gosselink, R.; Burtin, C.; Emtner, M.; Clini, Enrico; Chatwin, M.; Mitchell, S.
abstract

Not available

2015 - Impaired function in the complex patient with COPD: a matter to be considered [Articolo su rivista]
Clini, Enrico; Tonelli, Roberto
abstract

Not available

2015 - Insufficienza Respiratoria acuta e cronica (cap.21). [Capitolo/Saggio]
Clini, Enrico; Bonsignore, M; Confalonieri, Marco; Corrado, Arianna; Crisafulli, E; Fabbri, Leonardo; Longhini, F; Marchioni, Alessandro; Moretti, Matteo; Navalesi, P; Potena, A; Scala, R; Spanevello, A; Torregiani, C.
abstract

Non disponibile

2015 - La NIV nel paziente con insufficienza respiratoria cronica, la gestione domiciliare - Competenza specialistica nelle patologie pneumologiche pure [Articolo su rivista]
Marchioni, A.; Clini, Enrico; Beghe', Bianca
abstract

Questo capitolo ha lo scopo di revisionare la letteratura in merito ai meccanismi dell’insufficienza respiratoria cronica e gli effetti fisiologici e l’efficacia della ventilazione meccanica non invasiva nei pazienti affetti da BPCO in fase di stabilità clinica, cercando di dare indicazioni sulla selezione dei pazienti che potrebbero maggiormente beneficiare di questo trattamento.

2015 - Response to pulmonary rehabilitation: toward personalised programmes? [Articolo su rivista]
Ambrosino, N.; Clini, Enrico
abstract

Not available

2014 - A 6-week, home-based, unsupervised exercise training program is not effective in patients with chronic respiratory disease directly following a hospital admission [Rapid response to: BMJ 2014;349:g4315] [Articolo su rivista]
Spruit, M. A.; Rochester, C. L.; F., Pitta; R., Goldstein; T., Troosters; L., Nici; Zuwallack, R. L.; Clini, Enrico; Wouters, E. F. M.
abstract

Not available

2014 - A conceptual framework for reporting experience with physical activity in COPD. [Articolo su rivista]
Clini, Enrico; L., Fregonese
abstract

Not available

2014 - A core syllabus for postgraduate training in respiratory physiotherapy. [Articolo su rivista]
Pitta, F; Mitchell, F; Chatwin, M; Clini, Enrico; Emtner, M; Gosselink, R; Grant, K; Inal Ince, K; Lewko, A; Oberwaldner, B; Williams, J; Troosters, T.
abstract

Physiotherapy contributes significantly to improving quality of life for patients with respiratory disease. Physiotherapists specialised in dealing with respiratory pathology and its associated problems are not only central in the delivery of pulmonary rehabilitation but also provide strategies and techniques for exercise testing, airway clearance, breathlessness management, mobility and function improvement and pain management. Published evidence-based recommendations have paved the way for standardised practice while also unravelling the extended scope of responsibilities of the respiratory physiotherapist. The breakdown of traditional roles and allocation of new responsibilities is not confined to the respiratory physiotherapist within healthcare systems. Team-based healthcare and interprofessional treatment of patients is prevalent in the provision of care across the globe. New methods of healthcare delivery indicate that tasks are entrusted to those deemed competent to perform them. It has therefore been necessary to train allied health professionals to take over parts of clinical care.

2014 - An Official ERS Statement on Physical Activity in Chronic Obstructive Pulmonary Disease. [Articolo su rivista]
Watz, H; Pitta, F; Rochester, C; Garcia Aymerich, J; Zuwallack, R; Troosters, T; Vaes, A; Puhan, M; Jehn, M; Polkey, M; Vogiatzis, I; Clini, Enrico; Tooth, M; Gimeno Santos, E; Waschki, B; Esteban, C; Hayot, M; Casaburi, R; Porszasz, J; Mcauley, E; Singh, S; Langer, D; Wouters, E; Magnussen, H; Spruit, M. A.
abstract

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic respiratory disease affecting about 10% of the adult population above 40 years of age. Besides progressive chronic airflow limitation patients with COPD may also present multiple extra-pulmonary effects and comorbidities. This may, at least in part, be explained by the low levels of regular physical activity in patients with COPD. The “Global initiative for chronic Obstructive Lung Disease” has recommended regular physical activity for all patients with COPD. However, the clinical relevance of regular physical activity has not been addressed in depth. The purpose of this Official European Respiratory Society (ERS) Statement is to highlight the existing science regarding physical (in)activity in patients with COPD, including, but not limited to, its prevalence, determinants, consequences, measurement, and possible treatment.

2014 - Clinical highlights from the ERS congress in Barcelona. [Articolo su rivista]
Spruit, M. A.; M., Marvisi; J., Coolen; V., Poletti; S., Gasparini; B., Ställberg; Herth, F. J. F.; Clini, Enrico
abstract

This article reviews a selection of scientific presentations in the area of clinical problems at the 2013 European Respiratory Society Annual Congress in Barcelona, Spain. The article discusses the most relevant topics of interest in the field of clinicalrespiratory medicine, including breakthrough reports, and studies of particular interest to the healthcare professionals. Topics are presented and discussed in the context of the most up-to-date literature, including basic science and translational research. In particular, the reviewed topics especially deal with the areas of the complex chronic obstructive pulmonary disease and asthma even in the primary care setting, idiopathic pulmonary fibrosis (pathogenesis and therapy), advances in functional chest imaging, interventional pulmonology, pulmonary rehabilitation and chronic care. The 2013 European Respiratory Society (ERS) Annual Congress was held in Barcelona, Spain, with the largest worldwide attendance in the field of respiratory medicine (around 20.900 participants). A total of 4.401 abstracts were presented (77% acceptance rate), of which half dealt with clinical problems. Furthermore, outstanding lectures based on the most recent clinical updates were presented by international experts (1-6). The present article summarizes the most relevant topics of interest in the field of clinical respiratory medicine.

2014 - Comorbidities in Chronic Obstructive Pulmonary Disease from Assessment to Treatment. [Articolo su rivista]
Clini, Enrico; P., Boschetto; M., Lainsscak; W., Janssens
abstract

Not available

2014 - Differences in content and organizational aspects of pulmonary rehabilitation programs. [Articolo su rivista]
Ma, Spruit; F., Pitta; C., Garvey; Rl, Zuwallack; Cm, Roberts; Eg, Collins; R., Goldstein; R., Mcnamara; P., Surpas; K., Atsuyoshi; J., López Campos; I., Vogiatzis; Ja, Williams; S., Lareau; D., Brooks; T., Troosters; Sj, Singh; S., Hartl; Clini, Enrico; EFM W. o. u. t. e. r. s. On behalf of ERS Scientific Groups 0. 1., 02; 0. 9., 02; Aacvpr, ; ATS Pulmonary Rehabilitation, Assembly; ERS COPD Audit, Team
abstract

Objective: To study the overall content and organizational aspects of pulmonary rehabilitation programs from a global perspective to get an initial appraisal on the degree of heterogeneity worldwide. Methods: A twelve-question survey on content and organizational aspects was completed by representatives of pulmonary rehabilitation programs that previously participated in the European Respiratory Society (ERS) COPD Audit. Moreover, all ERS members affiliated with the ERS Scientific Groups 01.02 (Rehabilitation and Chronic Care) and/or 09.02 (Physiotherapy), all members of the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR), and all ATS Pulmonary Rehabilitation Assembly members were asked to complete the survey via multiple e-mailings. Results: The survey has been completed by representatives of 430 centres from 40 countries. The findings demonstrate large differences among pulmonary rehabilitation programs across continents for all aspects that were surveyed, including the setting, the case-mix of individuals with a chronic respiratory disease, composition of the pulmonary rehabilitation team, completion rates, methods of referral, and types of reimbursement. Conclusions: The current findings stress the importance of future development of process and performance metrics to monitor pulmonary rehabilitation programs, to be able to start international benchmarking, and to provide recommendations for international standards based on evidence and best practice.

2014 - Exercise performance after standard rehabilitation in COPD patients with lung hyperinflation. An observational multicentre cohort study. [Articolo su rivista]
E., Crisafulli; E., Venturelli; G., Biscione; G., Vagheggini; A., Iattoni; S., Lucic; N., Ambrosino; F., Pasqua; A., Cesario; Clini, Enrico
abstract

Background: The role of pulmonary rehabilitation (PR) in COPD patients with lung hyperinflation has not yet been fully investigated. Aim: In three Italian rehabilitation centres we retrospectively evaluated the effect of a standard PR course on exercise tolerance and symptoms according to the presence or absence of associated lung hyperinflation, as defined by lung function parameters. Methods: In a cohort of 823 COPD patients (age 71±8 yrs, FEV1 56±18 % pred.) we have systematically recorded: changes (D) in six minute walking test (6MWD) as the primary outcome; dyspnoea (D); muscle fatigue (F); SO2nadir during effort; perceived breathlessness score (MRC); and specific health related Quality-of-Life (SGRQ). Outcomes were compared between patients with lung hyperinflation (n=283, LH) or without (n=540 No-LH).Results: Groups were comparable for age, body mass index, baseline exercise tolerance, and breathlessness. D-6MWD (+72±47 vs +62±42 m, p<0.05); D-D (- 2.3±1.7 vs -1.9±1.3 point, p<0.05) and D-SO2nadir (+1.4±3.0 and +0.5±3.3 point, p<0.05) were greater in LH than in No-LH. Using a multivariate linear regression model, D-6MWD in the LH group significantly correlated with lower functional residual capacity (p=0.021) and baseline 6MWD (p=0.004).Conclusion: Tolerance, gas exchange and perceived symptoms during effort are the parameters that proved to gain a significant benefit from standard rehabilitation in COPD patients with a lung hyperinflation condition.

2014 - Fat Free Mass Depletion is Associated to Poor Exercise Capacity Irrespective of Dynamic Hyperinflation in COPD Patients. [Articolo su rivista]
E., Teopompi; P., Tzani; M., Aiello; S., Ramponi; F., Andrani; E., Marangio; Clini, Enrico; A., Chetta
abstract

BACKGROUND: In patients with COPD, we investigated the effect of the fat-free mass (FFM) on maximal exercise capacity and the relationship with changes in operational lung volumes during exercise. METHODS: In a cross-sectional study fifty-seven patients (16 females; age 65 ± 8 yrs) were consecutively assessed by resting lung function, symptom-limited cardiopulmonary exercise test, and body composition by means of bioelectrical impedance analysis to measure the FFM index (FFMI, kg/m2). RESULTS: Patients were categorized as depleted (n = 14) or non depleted (n = 43) according to FFMI. No significant difference in gender, age and in resting lung function was found between depleted and non depleted patients. When compared with non depleted, the depleted COPD patients had a significantly lower O2 uptake at peak of exercise and at anaerobic threshold as well as peak O2 pulse, O2 uptake efficiency slope (OUES) and heart rate recovery (HRR) (p < 0.05 for all comparisons), but similar inspiratory capacity/total lung capacity ratio at peak of exercise. Moreover, they also reported significantly higher leg fatigue (p < 0.05), but not dyspnea on exertion. In all patients, significant correlations (p < 0.01) were found between FFMI and peak O2Pulse, OUES, HRR and leg fatigue. CONCLUSIONS: This study shows that FFM depletion per se plays a part in the reduction of exercise capacity of COPD patients, regardless of dynamic hyperinflation, and is strictly associated to poor cardiovascular response to exercise and to leg fatigue, but not to dyspnoea.

2014 - Impaired arm activity in COPD: a questionable goal for rehabilitation. [Articolo su rivista]
Clini, Enrico; Ambrosino, N.
abstract

Not available

2014 - In COPD patients on prolonged mechanical ventilation Heart Rate Variability during the T-piece trial is better after Pressure Support Ventilation plus PEEP. A pilot physiological study. [Articolo su rivista]
M., Vitacca; S., Scalvini; M., Volterrani; Clini, Enrico; M., Paneroni; A., Giordano; N., Ambrosino
abstract

Objectives- To evaluate heart rate variability (HRV), hemodynamics, mechanics, dyspnea and blood gases following different mechanical ventilation (MV) settings. Background- No study has evaluated physiological changes during T-piece trials following different MV settings. Methods- In 8 COPD patients on prolonged MV we applied in random order two MV settings: i) pressure support (PS) 20cmH2O + positive end-expiratory pressure (PEEP) 0cmH2O (setting-1) and ii) PS 15cmH2O + PEEP 5cmH2O (setting-2), each followed by a 30-min T-piece trial. Results- Setting-1 induced greater minute ventilation, tidal volume/inspiratory time and lower pulmonary artery occlusion pressure; setting-2 reduced intrinsic PEEP. Mechanics and hemodynamics data did not differ, but all HRV time domain indices were reduced only after setting-1, suggesting a decreased parasympathetic and increased sympathetic cardiac modulation. Conclusions- The T-piece trial following setting-2 seems less stressful on neural control of HRV. Future studies on T-piece trials should consider the residual effect of the MV setting.

2014 - Multimorbidity in elderly patients with chronic obstructive pulmonary disease: stop smoking! Go exercise? [Articolo su rivista]
P. R., Burgel; Clini, Enrico
abstract

Not available

2014 - Poor adherence to guidelines for long-term oxygen therapy (LTOT) in two Italian university hospitals. [Articolo su rivista]
Verduri, Alessia; L., Ballerin; M., Simoni; M., Cellini; E., Vagnoni; P., Roversi; A., Papi; Clini, Enrico; Fabbri, Leonardo; A., Potena
abstract

Long-term oxygen therapy (LTOT) improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. Adherence to LTOT guidelines is problematic, both because efficacy has been demonstrated only in specific groups of COPD patients, and because it implies high costs. Introduces treatment high costs. The aim of our study was to examine retrospectively the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT between January 2005 and December 2006 in two Italian university hospitals (Ferrara and Modena). Out of a total of 191 medical records of patients prescribed LTOT, only 157 had adequate clinical data considering the three main criteria for appropriateness (arterial blood gas and/or pulse oximetry measurement, oxygen administration, smoking status). Out of these 157 patients, only 73 (46.5 %) fulfilled all three criteria recommended by the guidelines. Adherence was higher for LTOT prescribed by pulmonologists compared to internists. This survey showed that the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT is poor. Considering the high costs and the impact on the patients' quality of life of LTOT, these results suggest that the adherence should be carefully monitored.

2014 - Pulmonary Rehabilitation in Italy: professional barriers to overcome. [Articolo su rivista]
B., Balbi; N., Ambrosino; M., Lazzeri; F., Pasqua; M., Vitacca; Clini, Enrico
abstract

Not available

2014 - Rehabilitation and supportive therapy in elderly patients with COPD. [Articolo su rivista]
Crisafulli, E; Morandi, A; Olivini, A; Malerba, M; Clini, Enrico
abstract

Chronic Obstructive Pulmonary Disease (COPD) very often coexists with cardiovascular, musculoskeletal and metabolic comorbidities. This condition significantly impact on the general health, function, frailty and disability of such patients, and consequently on their prognosis. Indeed, complex and recurrent symptoms of general dysfunction are commonly present and burden on the health status. Symptomatic COPD patients, even with chronic and complex comorbidities or with different degree of severity, may benefit from rehabilitation including exercise and maintenance of physical activity, in order to reducing symptoms and restoring the highest possible level of independent function. This review will focus on the associated and relevant clinical problems of these patients at the onset of disability, methods of assessment and useful non-pharmacological treatments for caring and supporting them.

2014 - Strategie per migliorare la capacità di esercizio. [Capitolo/Saggio]
Clini, Enrico; Brogi, S; Salonini, E; Scorsone, D.
abstract

Non disponibile

2014 - Symptomatic elderly patients. The urgent need for comprehensive assessment and management [Articolo su rivista]
Clini, Enrico; Beghe', Bianca; Fabbri, Leonardo
abstract

Not available

2013 - An Official American Thoracic Society / European Respiratory Society Statement: Key concepts and advances in pulmonary rehabilitation - An Executive Summary. [Articolo su rivista]
Spruit, M. A.; Singh, S. J.; C., Garvey; R., Zuwallack; L., Nici; C., Rochester; K., Hill; Holland, A. E.; Lareau, S. C.; Man, W. D. C.; F., Pitta; L., Sewell; J., Raskin; J., Bourbeau; R:crouch, ; Franssen, F. M. E.; R., Casaburi; Vercoulen, J. H.; I., Vogiatzis; R., Gosselink; Clini, Enrico; Effing, T. W.; F., Maltais; J., Van der Palen; T., Troosters; Janssen, D. J. A.; E., Collins; J., Garcia Aymerich; D., Brooks; Fahy, B. F.; Puhan, M. A.; M., Hoogendoorn; R., Garrod; A., Schols; B., Carlin; R., Benzo; P., Meek; M., Morgan; Rutten van Mölken, M. P.; Ries, A. L.; B., Make; Goldstein, R. S.; Dowson, C. A.; Brozek, J. L.; Donner, C. F.; Wouters, E. F. M.
abstract

Background: Pulmonary rehabilitation is recognized as a core-component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. Purpose: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. Methods: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02 ‘Rehabilitation & Chronic Care’ determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed upon by all members. Results: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease (COPD), and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. Conclusion: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease.

2013 - COPD and metabolic syndrome: an intriguing association [Articolo su rivista]
Clini, Enrico; E., Crisafulli; A., Radaeli; M., Malerba
abstract

Chronic Obstructive Pulmonary Disease (COPD) has been recently recognized a condition involving not only the lungs. The presence of common factors in COPD and in other chronic extrapulmonary diseases, as well as the co-existence of these conditions in the same adult individual, support the hypothesis of a shared pathogenetic pathway.We will here review the interplay role between coexisting COPD and Metabolic Syndrome (MS), based on the most updated knowledge we will discuss this clinical condition from the definition, to the pathophysiology, and to the clinical implications.Basically, MS is more likely to be present in a COPD patients, and increased levels of circulatory pro-inflammatory proteins from both the lung and the adipose tissue coincide in these patients.Actually, the relative impact of the coexisting COPD and MS may depend on several factors: mainly the presence of physical inactivity and of systemic inflammation related to smoking habit,sedentary lifestyle, airways inflammation and obstruction, adipose tissue and inflammatory markers activation. More studies will be required to elucidate the association between COPD and MS andto formulate individualized management approaches for this specific disease phenotype.

2013 - Chronic Obstructive Pulmonary Disease is just one component of the complex multimorbidities in patients with COPD. [Articolo su rivista]
Clini, Enrico; Beghe', Bianca; Fabbri, Leonardo
abstract

Not available

2013 - Diagnosis of Chronic Obstructive Pulmonary Disease, simpler is better. Complexity and simplicity. [Articolo su rivista]
Clini, Enrico; E., Crisafulli; M., Roca; M., Malerba
abstract

So far, spirometry has always been the basis for diagnosis of COPD using FEV1/FVC fixed ratio or LLN, but no one of these two parameters is actually able to fully characterize the complex diagnostic features of this disease. Indeed, COPD presents additional and remarkable extra pulmonary and systemic manifestations which need to be captured and addressed. For this reason, the GOLD initiative have recently introduced the concept of a COPD staging and classification including factors which stand over the spirometric definition of the disease. Moreover, in the last decade, multidimensional indices such as BODE, ADO, DOSE, and COTE came up from research field in the appropriate attempt to "simplify the complex diagnosis" of a COPD patient. In particular,assessment of different phenotypes according to either clinical and biological features appears to be a still unmet expectation in helping the most accurate identification of each patients, thus providing a therapy targeted on his/her specified needs. In the era of the system biology, this olistic approach appears to be a real step forward a more accurate diagnosis, prognosis and cure rather than the assessment and identification of lung function and bronchodilating properties only in the COPD population.

2013 - Effect of rehabilitative exercise training on peripheral muscle remodelling in patients with COPD: targeting beyond the lungs [Articolo su rivista]
I., Nasis; Kortianou, E. A.; Clini, Enrico; Koulouris, N. G.; I., Vogiatzis
abstract

Locomotor muscle dysfunction and weakness are frequently observed in patients with Chronic Obstructive Pulmonary Disease (COPD). In addition to intolerable sensations of dyspnoea which importantly contribute to exercise limitation, intrinsic muscle abnormalities have also been implicated in inducing leg muscle fatigue/discomfort during exercise in these patients. It is, however, uncertain whether these intrinsic muscle abnormalities are linked to a specific 'myopathy' or they constitute a consequence of the disease. Besides muscle disuse, other factors which may contribute to peripheral muscle dysfunction include systemic inflammation, oxidative and nitrosative stress, chronic hypoxia, corticosteroid use and malnutrition. There is clear evidence that rehabilitative exercise training induces significant skeletal muscle fibre remodelling and improvements in functionality in the absence of changes in lung function. The ultimate purpose of this review is to identify and summarize the results of studies implementing diverse types of exercise training on peripheral muscle fibre phenotypic and genotypic modifications in patients with COPD.

2013 - Efficacy of Temporary Positive Expiratory Pressure (TPEP) in patients with lung diseases and chronic mucus hypersecretion. The UNIKO project: a multicentre randomised controlled trial. [Articolo su rivista]
E., Venturelli; E., Crisafulli; A., De Biase; D., Righi; P., Cavicchioli; G., Vagheggini; F., Dabrosca; B., Balbi; M., Paneroni; L., Bianchi; M., Vitacca; V., Galimberti; M., Zaurino; G., Schiavoni; A., Iattoni; N., Ambrosino; Clini, Enrico
abstract

Objective: To evaluate whether Temporary Positive Expiratory Pressure provides benefit in patients with lung diseases and chronic hypersecretion.Design: Single blind multicentre randomised trial.Setting: 5 Italian rehabilitation centres.Participants: 98 patients with Chronic Obstructive Pulmonary Disease and/or Chronic Bronchitis (n=78), or Bronchiectasis (n=20), with a Peak Cough Expiratory Flow >150 l/min and sputum production >30 mL/day, randomly included in two treatment groups. Interventions: For 10 consecutive days, Active group performed twice a day 20-min cycles of Manually Assisted Breathing Techniques in sequence with the addition of 15-min of Temporary Positive Expiratory Pressure, while Control group was treated by Manually Assisted Breathing Techniques alone.Measures: Within and between group changes of arterial oxygenation index, lung volumes and respiratory muscles strength were recorded at enrolment, after 3, and 10 treatment sessions. Pre-to-post treatment change of sputum volume and bronchial encumbrance (Δ-VAS), sputum density and purulence, were compared daily within the study period. Results: No significant changes were recorded for the oxygenation index, while dynamic lung volumes and respiratory muscle strength significantly (p <0.05) improved in Active group. The group comparison analysis of the pre-to-post change showed that Inspiratory Capacity was significantly higher in Active than in Control group (+19.5% and +2.2%, p=0.044) at day 10. A greater improvement in Δ-VAS was recorded in Active group at day 3 and 8. Conclusions: These preliminary data suggest that Temporary Positive Expiratory Pressure improves lung volumes and speeds up the improvement of bronchial encumbrance in patients with lung diseases and hypersecretion.

2013 - Feasibility and effectiveness of an educational program in italian COPD patients undergoing rehabilitation. [Articolo su rivista]
M., Paneroni; Clini, Enrico; E., Crisafulli; E., Guffanti; A., Fumagalli; A., Bernasconi; A., Cabiaglia; A., Nicolini; S., Brogi; N., Ambrosino; R., Peroni; L., Bianchi; M., Vitacca
abstract

Background. Self-management education is associated with improvement in quality of life and reduction of hospital admissions. Despite this, data are insufficient to formulate clearrecommendations regarding the type and content of education programs for COPD patients and few data are available on knowledge of the disease itself. Aim. To test: i) the level of patients’ knowledge of their disease and therapy at baseline and after an educational program (COPD-EP), ii) the feasibility of structured educational sessions, iii)influence of clinical status (degree of severity of disease, presence of comorbidities, oxygen use), demographics status (age, sex), previous knowledge level, previous lessons attendance and adherence of COPD-EP to the variation ofknowledge after program.Methods. Selected COPD inpatients and outpatients referred to Rehabilitative hospital departments were enrolled. The study was divided in two parts: i) Pre Study Phase (educational materials andhealth team preparation) and ii) Study Phase: all COPD patients received one educational brochure and were invited to attend seven 30-min group lessons to complete the educational program.Learning effect was evaluated by a 20-questions multiple choice Learning Questionnaire (LQ).Results. 158 patients were enrolled. 69.7 % of patients had previous formal education lessons on COPD management and 44.9 % had previous rehabilitative hospitalizations. At baseline, LQ total score was 15.2±3.5 points which increased to 16.9±3.0 point post COPD-EP (p<0.001). Pre-to-post change of LQ scores significantly correlated with adherence (R=0.24, p=0.002) and Severity Index of Cumulative Illness Rating Scale score (R= -0.22, p=0.001). Patients with low baseline knowledge were more likely to have improved LQ scores than patients with greater levels of knowledge. Patients without prior educational COPD lessons improved more than patients which attended previous education.Conclusions. A formal COPD-EP is feasible and effective in improving patient knowledge and self-management. Specific learning instruments to follow in this population should be validated.

2013 - High complexity rehabilitation in prolonged weaning patient: Role of pneumologist An Experts' Panel Position Paper [Articolo su rivista]
Vitacca, M.; Clini, E.; Nava, S.; Ambrosino, N.
abstract

Aim of this position paper is to recognize scientific specificity of patients under prolonged weaning from mechanical ventilation, to enhance the expertise of the respiratory physician in this field, to propose criteria of appropriateness and to discuss educational, organizational and technological standards of high complexity rehabilitation to offer to these patients. The document takes into account the definition of a patient with prolonged weaning; it analyzes the extent of the problem from the epidemiological point of view, the pathophysiological causes leading to this condition, the clinical and psychological consequences related to the quality of life and the social and health costs; finally, it also stresses the programs and methods of treatment, summarizes the main findings of the literature showing a photograph of the state of the art in Italy. There is already an important international consensus of the specific issues related to those patients under prolonged weaning. The creation of an italian network of specialized centers dedicated to "highly complex" rehabilitation may be the best cost/benefit answer to the dramatic economical impact that this population has on the Regional Health System.

2013 - La Riabilitazione Respiratoria. In: Malattie dell'Apparato Respiratorio (eds. L.M.Fabbri, S.A.Marsico)) [Monografia/Trattato scientifico]
Clini, Enrico; E., Venturelli; E., Crisafulli
abstract

Non disponibile

2013 - Mechanisms of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease [Articolo su rivista]
Roca, Mihai; Verduri, Alessia; Corbetta, Lorenzo; Clini, Enrico; Fabbri, Leonardo; Beghe', Bianca
abstract

Exacerbations of chronic obstructive respiratory disease (ECOPD) are acute events characterized by worsening of the patient's respiratory symptoms, particularly dyspnoea, leading to change in medical treatment and/or hospitalisation. AECOP are considered respiratory diseases, with reference to the respiratory nature of symptoms and to the involvement of airways and lung. Indeed respiratory infections and/or air pollution are the main causes of ECOPD. They cause an acute inflammation of the airways and the lung on top of the chronic inflammation that is associated with COPD. This acute inflammation is responsible of the development of acute respiratory symptoms (in these cases the term ECOPD is appropriate). However, the acute inflammation caused by infections/pollutants is almost associated with systemic inflammation, that may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (eg acute heart failure, thromboembolism, etc) almost invariably associated with COPD. Most concomitant chronic diseases share with COPD not only the underlying chronic inflammation of the target organs (i.e. lungs, myocardium, vessels, adipose tissue), but also clinical manifestations like fatigue and dyspnoea. For this reason, in patients with multi-morbidity (eg COPD with chronic heart failure and hypertension, etc), the exacerbation of respiratory symptoms may be particularly difficult to investigate, as it may be caused by exacerbation of COPD and/or ≥ comorbidity, (e.g. decompensated heart failure, arrhythmias, thromboembolisms) without necessarily involving the airways and lung. In these cases the term ECOPD is inappropriate and misleading.

2013 - Noninvasive mechanical ventilation with high pressure strategy remains a “double edged sword” ? [Articolo su rivista]
A., Esquinas; G., Siscaro; Clini, Enrico
abstract

Not available

2013 - Platelet activation as a novel mechanism of atherothrombotic risk in chronic obstructive pulmonary disease. [Articolo su rivista]
M., Malerba; Clini, Enrico; M., Malagola; Avanzi, G. C.
abstract

Chronic pulmonary Obstructive Disease (COPD) is characterised by pulmonary and systemic inflammation. In particular, the clinical course of this disease typically leads to periodic exacerbation involving inflammatory response and both respiratory and cardiovascular symptoms. Even though the exact mechanisms underlying the pathogenesis of COPD and its chronic and acute inflammation have not yet been fully understood, many studies have been highlighting the role of the endothelium, platelets (PTLs), and other circulating blood cells. PLTs themselves are crucial for haemostasis and, once activated by a number of different factors, will mediate endothelium adhesion and the rolling and activation of other circulating cells, such as neutrophils, which itself becomes a cause of cause tissue damage during the inflammatory process. The aim of this review is to highlight the onset of activation, thrombus formation, and inflammatory amplification with particular regard to the COPD patients and the course of their acute exacerbations.

2013 - Predicting walking-induced oxygen desaturations in COPD patients: a statistical model. [Articolo su rivista]
E., Crisafulli; A., Iattoni; E., Venturelli; Siscaro, Gherardo; C., Beneventi; A., Cesario; Clini, Enrico
abstract

Background- Oxygen desaturation during walking can have important consequence on prognosis of COPD patients. However, a standard 6-minute walking test (6MWT) useful to detect walking desaturators (WD+), can be difficult to execute in some settings of COPD management, as in the community health care service. Aim of our study was to validate and evaluate the accuracy of a newly composed score of risk of oxygen desaturation during walking in COPD patients: the Walking Desaturation Score-WDS. Methods- Data on symptomatic COPD inpatients admitted for rehabilitation (derivation cohort) and outpatients referred to the local community health service (validation cohort) were recorded. By pulse-oximetry oxygen saturation (SpO2) was monitored during 6MWT to obtain minimal values (SpO2 nadir); patients were thus divided into WD+ or non-desaturators (WD-). By a regression analysis model we have assigned a weighted score proportional to the measured percentage of explained variance for each variable. Risk estimate was computed by odds ratio (OR). A Receiver Operating Curve (ROC) analysis and a Hosmer-Lemeshow (HL) goodness of fit test were then performed to measure discrimination and calibration of WDS. Results- Baseline characteristics in derivation (n=435, WD+ 74%) and validation (n=238, WD+ 37%) cohorts were different. Resting arterial oxygen saturation-SO2, arterial partial pressure of oxygen-PaO2 and forced expiratory volume in the 1st second-FEV1 % pred. were the variables predicting walking desaturation. The proportion of WD+ patients (and OR estimate) gradually increased according to WDS (range 0 to 6) and associated categories of desaturation risk (low 0-1 in total score of WDS, high 2-3, and very high 4-6) (X2<0.001). A considerable predictive discrimination (area under curve-AUC 0.90, 95% CI 0.86 to 0.93, P< 0.001) and calibration (HL X2 1.31, P=0.859) values have been shown. Conclusions- WDS accurately predicts and classifies the risk of walking desaturation in COPD patients.

2013 - Pulmonary Rehabilitation Improves Cardiovascular Response to Exercise in COPD. [Articolo su rivista]
S., Ramponi; P., Tzani; M., Aiello; E., Marangio; Clini, Enrico; A., Chetta
abstract

Background: Pulmonary rehabilitation (PR) has emerged as a recommended standard of care in symptomatic COPD. Objectives: We now studied whether PR may affect cardiovascular response to exercise in these patients. Methods: Twenty-seven patients (9F; age: 69 yrs ± 8) with moderate to severe airflow obstruction admitted to a 9-week PR course performed a pre-to-post evaluation of lung function test and symptom-limited cardiopulmonary exercise test (CPET). Oxygen uptake (VO2), tidal volume (VT), dyspnoea and leg fatigue scores were measured during CPET. Cardiovascular response was assessed by means of oxygen pulse (O2Pulse), the oxygen uptake efficiency slope (OUES) and heart rate recovery at the 1st min (HRR). Results: A significant increase in peak VO2 and in all cardiovascular parameters (p<0.05) was found following PR, as compared to baseline. Leg fatigue (p<0.05), but not dyspnoea was significantly reduced after RP. When assessed at metabolic and ventilatory iso levels (%VCO2max and %VEmax), O2Pulse and VT were significantly higher (p<0.05) at submaximal exercise (75% and 50% of VCO2max and VEmax) after RP, when compared to baseline. VT percent changes at 75% VCO2max and 75% VEmax after RP significantly correlated with corresponding changes in O2Pulse (p<0.01). Conclusions: In COPD patients, a PR training program improved the cardiovascular response during exercise at submaximal exercise independent on the external workload. This change was associated with an enhanced ventilatory function during exercise.

2013 - Respiratory muscle training in patients recovering recent open cardio-thoracic surgery: a randomized-controlled trial. [Articolo su rivista]
E., Crisafulli; E., Venturelli; G., Siscaro; F., Florini; A., Papetti; D., Lugli; M., Cerulli; Clini, Enrico
abstract

Objectives- To evaluate the clinical efficacy and feasibility of an expiratory muscle training (EMT) device (Respilift™) applied to patients recovering from recent open cardio-thoracic surgery (CTS). Design- Prospective, double-blind, 14-day randomised-controlled trial. Participants and setting- 60 inpatients recovering from recent CTS and early admitted to a pulmonary rehabilitation program. Interventions- Chest physiotherapy plus EMT with a resistive load of 30 cm H2O for active group and chest physiotherapy plus EMT with a sham load for control group. Measures- Changes in maximal expiratory pressure (MEP) was considered as primary outcome, while maximal inspiratory pressures (MIP), dynamic and static lung volumes, oxygenation, perceived symptoms of dyspnoea, thoracic pain and well being (evaluated by visual analogic scale-VAS) and general health status were considered secondary outcomes. Results- All outcomes recorded showed significant improvements in both groups; however, the change of MEP (+34.2 mmHg, p<0.001 and +26.1%, p<0.001 for absolute and % of predicted, respectively) was significantly higher in Active group. Also VAS-dyspnoea improved faster and more significantly (p<0.05) at day 12 and 14 in Active group when compared with Control. The drop out rate was 6%, without differences between groups. Conclusions- In patients recovering from recent CTS specific EMT by Respilift™ is feasible and effective.

2013 - Selected clinical highlights from the 2012 ERS Congress in Vienna. [Articolo su rivista]
M., Marvisi; F. J. F., Herth; S., Ley; V., Poletti; N. H., Chavannes; M. A., Spruit; Clini, Enrico; V., Cottin
abstract

This article reviews a selection of scientific presentations at the 2012 annual meeting of the European Respiratory Society held in Vienna, Austria. The best abstracts from the groups of the Clinical Assembly (Clinical Problems, Rehabilitation and Chronic Care, Imaging, Interventional Pulmonology, Diffuse Parenchymal Lung Disease, and General Practice and Primary Care) are here presented and discussed in the context of the most updated literature. The reviewed topics especially deal with the area of chronic obstructive pulmonary disease (acute exacerbations, comorbidities, prognosis, rehabilitation), the diagnosis and management of idiopathic pulmonary fibrosis, sarcoidosis, endobronchial techniques in emphysema, functional imaging, and issues in respiratory medicine relevant for the primary care setting, including aspects related to the end-of-life and palliation.

2013 - Systemic inflammatory pattern of community-acquired pneumonia (CAP) patients with and without chronic obstructive pulmonary disease (COPD) [Articolo su rivista]
E., Crisafulli; R., Menendez; A., Huerta; R., Martinez; B., Montull; Clini, Enrico; A., Torres
abstract

BackgroundSeveral clinical studies have evaluated the role of chronic obstructive pulmonary disease (COPD) in community-acquired pneumonia (CAP) patients. We investigated the systemic inflammatory response of CAP patients with (CAP+COPD) and patients without associated COPD (CAP only).MethodsClinical, microbiological and immunological data were collected from367 prospective patients on admission towere collected at hospital admission during a 3-year period. Comparative analyses were performed between CAP+COPD (n=117) and CAP only patients (n=250) and between patients with and without domiciliary use of inhaled (ICS) and oral corticosteroids.ResultsDetailed characteristics of clinical severity and prognosis (mortality on hospitalization, at 30 days and at 90 days) were similar between CAP+COPD and CAP only patients. The re-admission rate and the frequency of a previous pneumonia were higher in the group of CAP+COPD patients. On day -1 (admission to hospital) CAP+COPD patients had significantly lower serum levels of tumour necrosis factor (TNF) α, interleukin (IL) 1 and IL-6 compared with CAP only patients; the remaining inflammatory biomarkers (C-reactive protein, procalcitonin, IL-8 and IL-10) were similar at days 1 and 3. The exclusion of patients with domiciliary use of ICS and oral corticosteroids confirms lower levels of TNF-α on day 1 in CAP+COPD patients. Finally, lower levels of IL-6 was were found only among those COPD patients who were currently using habitually used ICS.ConclusionOur prospective study demonstrates a different, disease-specific early inflammatory pattern between CAP patients with and without associated COPD; these finding are not completely corticosteroid-mediated.

2013 - Towards health benefits in chronic respiratory diseases: Pulmonary Rehabilitation [Articolo su rivista]
M., Spruit; Clini, Enrico
abstract

To date, pulmonary rehabilitation is defined by the ATS and ERS as a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies which include, but are not limited to, exercise training, education and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors. Daily symptoms, lower-limb muscle function, exercise capacity and health status will improve following pulmonary rehabilitation in individuals with chronic respiratory disease. Moreover, healthcare costs are likely to decrease following a pulmonary rehabilitation course. So, it seems fair to conclude that pulmonary rehabilitation is a cardinal part of COPD management, and a useful intervention in other chronic respiratory diseases. Taking all these facts into account, the Editorial Board of the European Respiratory Review decided to invite a group of international experts to write a review series on pulmonary rehabilitation

2012 - Anthropometry as Measure of Risk in COPD Patients (chapter 145) [Capitolo/Saggio]
E., Crisafulli; Costi, Stefania; Clini, Enrico
abstract

In the last decade, Chronic Obstructive Pulmonary Disease (COPD) has been redefined and newly approached not only as an airway-disease condition, but as a multi-component disease including extra-pulmonary manifestations, such as peripheral muscle weakness and malnutrition.The evaluation of body composition (as a part of nutritional assessment) fairly integrates the simple body mass index (BMI) measure by measuring the individual’s active metabolism (fat free mass, FFM). Indeed, BMI and FFM are both parameters correlated with many COPD-strong out- comes. In several epidemiological studies of COPD population admitted to both in- or outpatient rehabilitation programmes, the estimated prevalence of weight loss ranges from 17% to 53%. Nonetheless, weight reduction, together with FFM depletion, is a common feature in emphysema as well as in chronic bronchitis.A nutritionally depleted patient is usually defined by a BMI of £ 20 kg/m2. Several studies aimed at evaluating the prognostic value of BMI in COPD patients have documented that BMI £ 25 kg/m2 and weight reduction of >3 kg/m2 are strong predictors of mortality. Moreover, other studies confirmed that FFM and measurement of the cross-sectional area of muscle mass (mid-thigh and mid-arm) also correlate to survival rates.In future research, studies looking at other anthropometric, metabolic and functional factors able to predict the long-term survival should be welcomed in patients with other diseases, such as pul- monary fibrosis, similarly leading to chronic respiratory failure.

2012 - COPD in the elderly is almost invariably associated with one or more chronic comorbidities [Relazione in Atti di Convegno]
Verduri, A; Roca, M; Bortolotti, M; Garofalo, M; Balduzzi, S; Veronesi, J; Leuzzi, C; Clini, Enrico; Modena, Maria Grazia; Fabbri, Leonardo; Beghe', Bianca
abstract

non presente

2012 - Clinical highlights from the 2011 ERS Congress in Amsterdam [Articolo su rivista]
M. A., Spruit; N. H., Chavannes; F. J. F., Herth; V., Poletti; S., Ley; O. C., Burghuber; Clini, Enrico; V., Cottin
abstract

This review article reports selected news pertinent to most important clinical problems in the field of respiratory medicine. Expert authors from the Clinical Assembly have selected updated reports related to the presentations at the 2011 annual meeting of the European Respiratory Society held in Amsterdam (TheNetherlands), where more than 20,000 attendants met. The hot topics and selected abstracts from the study groups of the Clinical Assembly are discussed here in the context of recent literature.

2012 - Clinical highlights from the 2011 ERS Congress in Amsterdam [Repere clinice de la Congresul ERS 2011 de la Amsterdam] [Articolo su rivista]
Spruit, M. A.; Chavannes, N. H.; Herth, F. J. F.; Poletti, V.; Ley, S.; Burghuber, O. C.; Clini, E.; Cottin, V.
abstract

This article reports on selected papers pertinent to the most important clinical problems in the field of respiratory medicine. Expert authors from the Clinical Assembly of the European Respiratory Society (ERS) have selected updated reports related to presentations given at the 2011 ERS Annual Congress, which was held in Amsterdam (the Netherlands) and attended by more than 20,000 participants. The hot topics and selected abstracts from the scientific groups of the Clinical Assembly are discussed here in the context of recent literature.

2012 - Pulmonary rehabilitation following radical chemo-radiation in locally-advanced non surgical NSCLC: preliminary evidences. [Articolo su rivista]
F., Pasqua; D'Angelillo, ; F., Mattei; S., Bonassi; Biscione, G. L.; K., Geraneo; V., Cardaci; L., Ferri; S., Ramella; P., Granone; S., Sterzi; E., Crisafulli; Clini, Enrico; F., Lococo; L., Trodella; A., Cesario
abstract

Non disponibile (letter)

2012 - Rehabilitation, Weaning and Physical Therapy Strategies in the Critically Ill patients [Articolo su rivista]
N., Ambrosino; Venturelli, Elena; G., Vagheggini; Clini, Enrico
abstract

In critically ill patients prolonged hospital stay as a consequence of the initial acute insult, combined with adverse side effects of drug therapy, often on the background of chronic disease, causes severe late complications like muscle weakness, prolonged symptoms, mood alterations and poor health-related quality of life. The clinical aims of physical rehabilitation for patients in both medical and surgical intensive care units (ICUs) are focussed on the patient as a whole to improve short- and even long-term care of patients admitted to these units.Purpose of this review article is to sum up the currently available evidence of comprehensive rehabilitation programs in critically ill patients, with a description of the key components and techniques used particularly in those individuals specifically admitted to specialised ICUs.Despite literature suggesting that several techniques have led to beneficial effects, and that muscle training is associated with weaning success, the scientific evidence is limited. Although there are limitations associated with undertaking comparative studies in the intensive care environment, further studies with solid clinical short- and long-term outcome measures are now welcomed.

2011 - Advanced COPD patients under home mechanical ventilation and/or long term oxygen therapy: italian health care costs. [Articolo su rivista]
M., Vitacca; L., Bianchi; A., Bazza; Clini, Enrico
abstract

Introduction. Little information is available on health care costs for patients with very severe chronic obstructive pulmonary disease The aim of the current work was to evaluate Italian health care costs in these patients. Patients and Methods. Prospective 1-year analysis were assessed in three subgroups of patients; non-invasively ventilated (n=30); invasively-ventilated (n=12) and on long-term oxygen therapy (n= 41). Acute costs for care were a sum of fees for doctor’s consultations, admissions to hospital (ward and intensive care unit) and emergency drugs. Chronic costs were the sum of costs for pharmacotherapy and home ventilation and/or oxygen care. Results. Mean cost/day/patient was 96±112 € (range 9-526 €), with acute costs accounting for 72% and chronic costs for 28% of the total cost burden, with no significant differences in costs associated with the three subgroups. Acute costs had a non-normally distribution (range 0 to 510 €) with cost for hospitalization being the highest cost burden with greater than 30 % of acute care costs were attributed to only a small segment of patients. Chronic care costs were also unevenly distributed among the various groups (ANOVA p=0.006), with home oxygen supply being the highest cost burden. Conclusions. The current Health Care System is in urgent need for a reassessment of the high cost burden associated with hospitalizations and home oxygen supply.

2011 - COPD and comorbidities: The importance of the disease management [Articolo su rivista]
Clini, E. M.; Beghe, B.; Crisafulli, E.; Fabbri, L. M.
abstract

2011 - Co-morbidities in chronic respiratory patients: limitations or opportunities for caring ? [Articolo su rivista]
E., Crisafulli; Venturelli, Elena; Iattoni, Andrea; Clini, Enrico
abstract

In the population of chronic respiratory patients a new subset with clinical complexity and with multiple coexisting organ failure and diseases is rapidly growing. Mainly due to the aging process, the associated frailty - not strictly related to the patient’s age - consists in a progressive and physiologic decline in multiple body systems leading to a substantial loss of functions and physiologic reserve. It is commonly acquainted that frailty, co-morbidities (several medical conditions associated) and disability (decline in physical functions) overlap each other: both frailty and co-morbidities can predict physical disability, whereas disability per se may exacerbate frailty and co-morbidities. Specific interventions (as rehabilitation) targeting at the physical activity the old population have been shown to improve physical function and have a benefit along the full spectrum of health status. However, there is a substantial need for a multidimensional and personalized care approach: patient’s complexity, in fact, may play a role in determining the patient’s response to treatment. In particular, each disease as a single entity might reduce the response to treatment, depending on its effect on body functions and target therapies. Notwithstanding, the clinical complexity of these patients and the presence of several co-morbidities, does not preclude per se the application and the effectiveness of a comprehensive rehabilitation program targeted to the individual’s needs.

2011 - Complessità del paziente con insufficienza respiratoria cronica associata a BPCO [Articolo su rivista]
F., Sgambato; Clini, Enrico
abstract

Article Outline-Introduzione-Epidemiologia-Complessità e fisiopatologia-Patogenesi-Ventilazione alveolare-Capacità funzionale residua, rapporto ventilazione/perfusione, pressione dell’arteria polmonare-Quantità di acqua intrapolmonare e/o intratoracica-Terapia-Interventi non farmacologici-Conclusioni

2011 - Dynamic Hyperinflation is Associated with a Poor Cardiovascular Response to Exercise in COPD Patients. [Articolo su rivista]
P., Tzani; M., Aiello; D., Elia; L., Boracchia; E., Marangio; D., Olivieri; Clini, Enrico; A., Chetta
abstract

Background: Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. Methods: We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. Results: Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75 % as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg ∙ bpm (0.720 sensitivity and 0.783 specificity), respectively. Conclusion: The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.

2011 - Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnoea in COPD patients. A pilot study. [Articolo su rivista]
P., Tzani; E., Crisafulli; G., Nicolini; M., Aiello; Chetta, Alfredo Antonio; Clini, Enrico; D., Olivieri
abstract

Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnoea and exercise capacity limitation.Objectives: the present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control.Methods: COPD patients with FEV1 <65% and plethysmographic functional residual capacity 120% of predicted were randomized to a double-blind, double-dummy, 12 week, parallel group, treatment with either BDP/F 400/24 µg/day or FP/S 500/100µg/day. Lung volumes were measured with full body plethysmography and dyspnoea was measured with transition dyspnoea index.Results: 18 patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnoea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F vs. FP/S. Conclusion: BDP/F extra-fine combination is effective in reducing air trapping and dyspnoea in COPD patients with lung hyperinflation.

2011 - Energy expenditure at rest and during walking in patients with chronic respiratory failure: a prospective two-phase case-control study [Articolo su rivista]
E., Crisafulli; C., Beneventi; V., Bortolotti; N., Kidonias; Fabbri, Leonardo; A., Chetta; Clini, Enrico
abstract

Measurement of Energy Expenditure (EE) at rest (REE) and during physical activities are increasing in interest in chronic patients. In this study we aimed at evaluating the validity/reliability of the SenseWear®Armband (SWA) device in terms of REE and EE during assisted walking in Chronic Respiratory Failure (CRF) patients receiving long-term oxygen therapy (LTOT).In a two-phase prospective protocol we studied 40 severe patients and 35 age-matched healthy controls. In phase-1 we determined the validity and repeatability of REE measured by SWA (REEa) in comparison with standard calorimetry (REEc). In phase-2 we then assessed EE and Metabolic Equivalents-METs by SWA during the 6-minute walking test while breathing oxygen in both assisted (Aid) or unassisted (No-Aid) modalities. When compared with REEc, REEa was slightly lower in patients (1351±169 vs 1413±194 kcal/day respectively, p<0.05), and less repeatable ithan in healthy controls (0.14 and 0.43 coefficient respectively). COPD patients with CRF patients reported a significant gain with Aid as compared with No-Aid modality in terms of meters walked, perceived symptoms and EE.SWA provides a feasible and valid method to assess the energy expenditure in CRF patients on LTOT, and it shows that aided walking results in a substantial energy saving in this population.

2011 - Functional recovery following physical training in tracheotomised and chronically ventilated patients. An observational prospective cohort study. [Articolo su rivista]
Clini, Enrico; Crisafulli, E; Degli Antoni, F; Beneventi, C; Costi, Stefania; Fabbri, Leonardo; Nava, S.
abstract

Background: Rehabilitation is a non-pharmacological therapy able to restore health status and reversing the patient’s disability. Since the efficacy of this treatment in critically ill patients is not enough documented, the present study aimed to assess whether the degree of change in individual’s functional status after comprehensive rehabilitation may influences the in-hospital clinical outcomes in a population of long-term ventilated patients.Methods: In a prospective cohort study we observed 77 tracheotomized patients (aged 75±7 yrs) admitted for difficult weaning in a regional weaning centre (RICU). Care plan including peripheral muscle training was delivered on a daily basis. Demographic, anthropometric and functional characteristics were measured at admission in all patients. Pre-to-post change in basic activity of daily living score (Δ-BADL), survival and weaning success rate were recorded as clinical outcomes. Pearson’s correlation analysis and a linear regression model with Δ-BADL as the dependent variable were performed to test the predictive power of any measurement taken at baseline.Results: Sixty-seven patients (87%) survived whereas 55 of them (74%) succeded weaning during stay in RICU. Δ-BADL was +2.53 point (SD 2.03, median 2). Performance of the broadest muscle of back (BMB) at baseline predicted Δ-BADL (β 0.388, 95% CI 0.111-1,664, p=0.026). Probability to remain ventilator-free (p=0.043) and to survive (p=0.001) differed across the categories of Δ-BADL (0=no change, 1-2=least improvement, and >2=improvement above median change). Conclusions: Mortality rate and weaning success vary according to the degree of change in basic activities following active training in tracheotomised, ventilated and difficult-to-wean patients. Broadest muscle of back performance was the only significant predictor of change in these activities.

2011 - Non-invasive ventilation in elderly patients with acute hypercapnic respiratory failure: a randomized controlled trial. [Articolo su rivista]
Nava, S; Grassi, M; Fanfulla, F; Domenighetti, G; Carlucci, C; Perren, A; Dell’Orso, D; Vitacca, M; Ceriana, P; Clini, Enrico
abstract

Background Older patients usually receive less invasive and costly hospital care, especially if they meet the criteria for Intensive Care Unit (ICU) admission or have a ‘do not intubate’(DNI) order. Objective: The aim of this randomized, control trial was to assess the effectiveness of non-invasive mechanical ventilation (NIV) vs standard medical therapy (SMT) in reducing the need of intubation, improving survival and reducing respiratory distress in very old patients with acute hypercapnic respiratory failure.Methods: Eighty-two patients aged >75 years (mean age 81.3±3.5 years) with acute hypercapnic respiratory failure were randomized to receive NIV or SMT Results: primary outcome was the need of meeting the intubation criteria (ETIc);secondary outcomes were: 12-months mortality “history”; respiratory rate, dyspnea score, and arterial blood gases.Meeting the ETIc was lower in the NIV in comparison with SMT group (7.3 vs. 63.4% of patients, respectively; p<0.001), as well as the mortality risk (OR=0.40; 95%CI: 0.19-0.83; p=0.014). 22/41 SMT patients with DNI received NIV as a “rescue” therapy. The risk of death in this latter group was comparable with the NIV group and significantly lower than in those patients receiving ETI(OR=0.60, 95%CI: 0.18-1.92 vs. 4.03, 95%CI: 2.35-6.94, respectively; p=0.009). Arterial blood gases, respiratory rate and dyspnoea improved significantly faster with NIV than with SMT.Conclusions Compared to SMT, NIV decreased the meeting of ETIc, and the mortality “history” of very old patients with AHRF. NIV should be offered as an alternative to patients considered poor candidates for intubation and those with a DNI order.NCT00600639 at: www.ClinicalTrials.gov

2011 - Palliative care for patients affected by non oncological advanced and chronic diseases. Position Paper by Italian Association of Hospital Pneumologists, in collaboration with SIAARTI and ARIR [Articolo su rivista]
Vitacca, M.; Clini, E.; Ambrosino, N.; Nava, S.; Vianello, A.; Orsi, L.; Vagheggini, G.; Moretti, F.; Lazzeri, M.; Paneroni, M.; Vitulo, P.; Morales, J.; Bonito, V.; Malacarne, P.; Cuomo, A. M.; Marchese, S.; Redaelli, D.; Gristina, R.; Barbisoni, M.; Scala, R.
abstract

2011 - Rehabilitation in COPD patients admitted for exacerbation [Articolo su rivista]
Clini, Enrico; E., Venturelli; E., Crisafulli
abstract

Recovery of lung function is delayed up to 2 months following acute exacerbation (AE) of COPD patients. After AE, even with optimal medical therapy, it takes considerable time for COPD patients to recover to baseline ability to perform usual physical activity.Despite pulmonary rehabilitation (PR) has been so far considered a useful non-pharmacological therapy in stable COPD individuals, still few studies have examined the effect of rehabilitation during and/or early after AE.The present review updates the application of early PR and main physical therapies both during hospital acute care and following discharge of COPD patients undergoing exacerbation.Only recently, literature has shown feasibility and effectiveness of early PR in COPD patients undergoing AE. Notwithstanding, it clearly appears a treatment indicated just after or even during an acute episode in hospital.Future studies should be able to clarify the practical role and effects of a timely application of rehabilitation to acute COPD, as well as the preferred modalities, duration and techniques to apply in this condition.

2011 - Rehabilitation in COPD patients: evergreen in Pneumology and beyond. [Articolo su rivista]
Clini, Enrico; N., Ambrosino
abstract

Several studies have shown so far that pulmonary rehabilitation (PR) has a beneficial effect on symptoms and on Health Related Quality of Life (HRQoL) in stable COPD patients.Nowadays major effort should be addressed to implement optimal rehabilitation regimens focused on individual needs, clarifying the effects of different PR components, exercise modalities and feasible settings. In this issue of the journal the first review article of a new series “Novelties in Pulmonary Rehabilitation” dealing with all these innovative aspects associated to the rehabilitation of COPD patients is invited (see also table 1). As the guest editors of these review articles we have chosen 5 main topics of interest to assure readers of some of the hot topics and/or unanswered questions on the clinical ground.

2011 - Rehabilitation in Critically Ill Patients [Articolo su rivista]
E., Venturelli; E., Crisafulli; F., Degli Antoni; L., Trianni; Clini, Enrico
abstract

Prolonged stay in the hospital and difficult response to pharmacotherapy can often lead to severe complications in critically ill patients for muscle weakness, physical deconditioning, recurrent symptoms, mood alterations, and poor quality of life. Rehabilitation is a treatment able to expand short- and long-term management of chronic patients admitted to intensive care. Recovery of individual’s physical and respiratory functions are both aims of a rehabilitation course in this area.The purpose of this review article is to resume a ‘‘state of art’’ of the currently available evidence for a rehabilitation strategy in critically illpatients, with a description of the main activities and techniques adopted.Despite the use of several activities and techniques that have led to short-term beneficial effects on both pulmonary and physical functions,muscle retraining represents the most important evidence-based aspect of Intensive Care Unit-rehabilitation: indeed, it is associated with weaning success and helps patients to recover at their maximum at discharge.

2011 - Safety and efficacy of short-term intrapulmonary percussive ventilation in patients with bronchiectasis [Articolo su rivista]
Paneroni, M; Clini, Enrico; Simonelli, C; Bianchi, L; Degli Antoni, F; Vitacca, M.
abstract

Background. Treatment of bronchiectasis includes drugs, oxygen therapy and bronchial clearance maneuvers. The aim of the current study was to assess safety and efficacy of IntrapulmonaryPercussive Ventilation when compared with usual Chest Physical Therapy in patients with bronchiectasis Methods. In two consecutive days, 22 patients underwent both Intrapulmonary Percussive Ventilation and Chest Physical Therapy following a randomized cross-over design. At inclusion (T0), at the end of 30-min session (T1), and after 30 min (T2) and 4 hrs (T3), side effects, heart rate, oxygen saturation rate, respiratory rate, sensation of phlegm encumbrance and dyspneameasured by visual analogue scales, were recorded. At T1, discomfort measured by visual analogue scales was also recorded. At T3, we evaluated efficacy in terms of volume (ml), and wet and dry weight (g) of sputum. Results. Side effects were not so severe as to determine study discontinuation and were similar (27%) between the two treatments. Heart rate (p<.001) and respiratory rate (p=0.047) decreased over time while sensation of phlegm encumbrance improved (p=0.026) withboth treatments. Only Intrapulmonary Percussive Ventilation improved (p=0.004) sensation of dyspnea and resulted more comfortable than Chest Physical Therapy (p=0.032). The two treatments caused important phlegm production without differences in total volume, and both wet and dry weight. Conclusions. In patients with bronchiectasis and productive cough, short-term application of Intrapulmonary Percussive Ventilation is similarly safe and effective than traditional chestPhysical Therapy with less discomfort. Further studies on cost-effectiveness of using IPV is recommended.

2011 - Selected clinical highlights from the ERS congress. [Articolo su rivista]
C., Robalo Cordeiro; S., Singh; F., Herth; S., Ley; Chavannes, N. H.; Clini, Enrico; V., Cottin
abstract

This article reviews a selection of presentations at the 2010 annual meeting of the European Respiratory Society held in Barcelona, Spain, which was the largest congress ever in the field of respiratory medicine. The best abstracts from the groups of the clinical assembly (clinical problems, rehabilitation and chronic care, imaging of the lung, interventional pulmonology, diffuse parenchymal lung disease, and general practice and primary care) are presented in the context of the current literature. The 2010 European Respiratory Society (ERS) meeting congress was held in Barcelona, Spain, September 18-22, 2010. The largest congress ever in the field of respiratory medicine included a large programme, with both presentation of original scientific presentations with published abstracts, and many symposia devoted to synthetic presentation of medical literature and experience. Here is reported an overview of the abstracts of the Clinical Assembly based on scientific merit, novelty, and relevance. Due to space constraints, only a non-exhaustive selection in the field of the six scientific groups of this Assembly can be presented. They cover the spectrum of clinical problems, rehabilitation and chronic care, imaging of the lung, interventional pulmonology, diffuse parenchymal lung disease, and general practice and primary care.The 2010 European Respiratory Society (ERS) meeting congress was held in Barcelona, Spain, September 18-22, 2010. The largest congress ever in the field of respiratory medicine included a large programme, with both presentation of original scientific presentations with published abstracts, and many symposia devoted to synthetic presentation of medical literature and experience. Here is reported an overview of the abstracts of the Clinical Assembly based on scientific merit, novelty, and relevance. Due to space constraints, only a non-exhaustive selection in the field of the six scientific groups of this Assembly can be presented. They cover the spectrum of clinical problems, rehabilitation and chronic care, imaging of the lung, interventional pulmonology, diffuse parenchymal lung disease, and general practice and primary care.

2011 - Sub-clinical left ventricular diastolic dysfunction in early stage of chronic obstructive pulmonary disease [Articolo su rivista]
M., Malerba; B., Ragnoli; M., Salameh; G., Sennino; M. L., Sorlini; A., Radaeli; Clini, Enrico
abstract

Sub-clinical cardiac dysfunction may be significantly associated with chronic obstructive pulmonary disease (COPD) with different degree of severity. In a cross-sectional design we aimed at evaluating the frequency of left ventricular diastolic dysfunction (LVdd) and its correlation with lung function, pulmonary arterial pressure and systemic inflammation in a selected population of COPD at an early stage of their disease. Fifty-five COPD patients with no clinical signs of cardiovascular dysfunction were recruited and compared to 40 matched healthy controls. All the subjects underwent pulmonary function testing, doppler echocardiography, and interleukin 6 blood sampling. Presence of LVdd was defined and according to the significant change in both the ratio between early and late diastolic transmitral flow velocity (E/A ratio), isovolumetric relaxation time (IVRT), and deceleration time (DT) . The frequency of LVdd was higher in COPD group (70,9%) compared to controls (27,5%). In these patients decreased E/A ratio, and prolonged IVRT and DT clearly pointed to left ventricular filling impairment, a condition we found to be especially severe in those patients suffering from lung static hyperinflation as expressed by inspiratory-to-total lung capacity ratio (IC/TLC) <0.25. Circulating levels of interleukin 6 as well were higher among COPD patients compared to controls. The results of the present study suggest that sub-clinical left ventricular filling impairment is frequently found in COPD patients at the earlier stage of the disease even in the absence of any other cardiovascular dysfunction. Doppler echocardiography may help the early identification of LVdd in COPD patients .

2010 - Early rehabilitation: much better than nothing [Articolo su rivista]
Clini, Enrico; P., Roversi; E., Crisafulli
abstract

Not available

2010 - Efficacy of standard Rehabilitation in COPD Outpatients with Co-morbidities. [Articolo su rivista]
Crisafulli, E; Gorgone, P; Vagaggini, B; Pagani, M; Rossi, G; Costa, F; Guarriello, V; Paggiaro, P; Chetta, A; de Blasio, F; Olivieri, D; Fabbri, Leonardo; Clini, Enrico
abstract

A prospective study was performed to 1) confirm the prevalence pattern of the most frequent co-morbidities and 2) evaluate whether characteristics of patients, specific co-morbidities, and increasing number of co-morbidities are independently associated with poorer outcomes in a population of complex COPD submitted to rehabilitation (PR). Three-hundred and sixteen outpatients (age 68±7 yrs) were studied. Co-morbidities and proportion of patients with a pre-defined minimally significant change in exercise tolerance (6MWD, +54 mt), breathlessness (MRC score, -1 point) and quality-of-life (SGRQ, -4 points) as outcomes were recorded. Sixty-two % of patients reported co-morbidities; systemic hypertension (35%), dyslipidemia (13%), diabetes (12%), and coronary disease (11%) were the most frequent. Above 45% of them improved over MCID in all the outcomes. In a logistic regression model, baseline 6MWD (OR 0.99 95%CI 0.98-0.99, p=0.001), MRC (OR 12.88 95%CI 6.89-24.00, p=0.001), and PaCO2 (OR 1.08 95%CI 1.00-1.15, p=0.034) related with the proportion of patients who improved 6MWD and MRC, respectively. Presence of osteoporosis reduced the success rate in 6MWD (OR 0.28 95%CI 0.11-0.70, p=0.006). A substantial prevalence of co-morbidities in COPD outpatients referred to rehabilitation was confirmed. The individual’s disability and the presence of osteoporosis only were independently associated with poorer rehabilitation outcomes. (registered at ClinicalTrials.gov: NCT00992498.)

2010 - Insufficienza Respiratoria acuta e cronica [Capitolo/Saggio]
Corrado, A; Crisafulli, E; Moretti, M; Nava, S; Clini, Enrico
abstract

Trattazione della fisiopatologia eclinica della insufficienza respiratoria acuta ecronica; guida alle terapie correnti (razionale, obiettivi, indicazioni, efficacia)

2010 - La broncopneumopatia cronica ostruttiva nell'anziano [Capitolo/Saggio]
Beghe', Bianca; Fabbri, Leonardo; Clini, Enrico
abstract

La broncopneumopatia cronica ostruttiva (BPCO) rappresenta una affezione a carico dell’apparato respiratorio di frequente riscontro nella popolazione adulta, di elevato impatto epidemiologico nella fascia di età oltre i 50 anni, con manifestazioni cliniche rilevanti in fase avanzata di malattia, in un paziente tipicamente anziano e che presenta, al tempo stesso numerose altre patologie croniche concomitanti, dette comorbilità.Questa caratteristica determina un modello clinico di paziente complesso che, oltre alle caratteristiche legate alla patologia respiratoria, presenta rilevanti effetti patologici extrapolmonari che pure necessitano di essere riconosciuti e trattati.Nel presente capitolo discuteremo appunto, partendo dalla malattia respiratoria, i fondamentali elementi patogenetici, clinici e terapeutici che identificano il paziente anziano con la BPCO.

2010 - La broncopneumopatia cronica ostruttiva nell'anziano. In: M.Mongardi (ed) L'Assistenza all'Anziano. [Monografia/Trattato scientifico]
Beghe', Bianca; Fabbri, Leonardo; Clini, Enrico
abstract

Nel capitolo vengono delineati gli aspetti epidemiologici, diagnostici, clinici e terapeutici della BPCO, patologia di assoluto rilievo nell'età avanzata. Completano il capitolo aspetti di integrazione dell'assistenza professionale nella patologia in oggetto.

2010 - Last 3 months of life in home ventilated patients: the family perception [Articolo su rivista]
M., Vitacca; M., Grassi; N., Hill; L., Barbano; V., Galavotti; C., Sturani; A., Vianello; E., Zanotti; L., Ballerin; A., Potena; R., Scala; A., Peratoner; P., Ceriana; L., Di Buono; Clini, Enrico; N., Ambrosino; S., Nava
abstract

Background: Information on quality of care in end-stage home ventilated patients is lackingMethods: To describe the family’s perception of quality of care delivered to these patients during the last 3 months of life, 11 Respiratory Units proposed a questionnaire to close relatives of 168 deceased patients. Results: Response rate was 98.8%. Answers to the binary 35-item questionnaire were distributed into just 4 groups (COPD or non-COPD and tracheostomized or NIV users) for each of 6 identified domains (Control of symptoms, awareness of disease, family burden, process of dying, medical troubles, technical problems). More than 80% of patients were thought to be conscious of their illness, and only 59% had satisfactory control of symptoms, while who did not, mainly COPD patients (50%), required increased use of drugs. 46% of patients died at home, but a large portion (83%) of COPD patients required hospital admission (mainly in ICU) during the last 3 months of life. NIV patients required more technical interventions and settings adjustments than tracheotomized patients (20% and 12 % p=0.038, respectively), irrespective of the diagnosis. Conclusions: Close relatives of home ventilated patients in their last 3 months of life, perceive that most of their beloved have high awareness of prognosis. Symptoms control was not always achieved and COPD patients and those with NIV needed more frequent health care assistance, notwithstanding, half of patients died at home. This report suggests a stronger way forward improvement in the quality of care in terminally-ill ventilated patients.

2010 - Learning impact of education during pulmonary rehabilitation program. An observational short-term cohort study [Articolo su rivista]
Crisafulli, E; Loschi, S; Beneventi, C; De Biase, A; Tazzioli, B; Papetti, A; Lorenzi, C; Clini, Enrico
abstract

Background: Among the several components integrating a pulmonary rehabilitation (PR) course, education may contribute to the individual’s recognition of symptoms and worsening of the disease. However, the specific gain of education is far to be clearly documented to the health care providers. Aim of our preliminary study was to assess the learning impact of educational sessions (ES) in Chronic Obstructive Pulmonary Disease (COPD) patients referred to standard PR.Methods: Six ES on 3 areas (Symptoms-Therapies, Aids, Mood) were applied during PR at our clinic. The learning effect was prospectively evaluated by a specific questionnaire (ESQ) in 285 COPD patients (age 69±8 years, FEV1 53±14 % pred), then grouped into those who have completed ES (Completers group, n=226) or who did not (mean 2±1 ES) (Control group, n=59). Total and partial ESQ scores, and PR outcomes (6-minute walking test-6MWD, effort-dyspnoea at Medical Research Council scale-MRC, and health-related quality of life scale-SGRQ) were assessed in a pre (T0) to post (Tend) design.Results: Similar improvement in PR outcomes was recorded in both groups at Tend, whereas ESQ total and partial scores significantly increased in Completers only (p&lt;0.001). ESQ-Aids score improved to a greater extent in Completers than in Control (+0.60±1.03 vs +0.27±1.27 point respectively, p=0.036). A higher proportion of Completers improved above the median change of both ESQ total and aids scores (p&lt;0.05).Conclusion: Attending educational sessions produces a specific short-term learning effect during rehabilitation of COPD patients.

2010 - Measures of dyspnea in pulmonary rehabilitation. [Articolo su rivista]
E., Crisafulli; Clini, Enrico
abstract

Dyspnea is the main symptom perceived by patients affectedby chronic respiratory diseases. It derives from a complex interaction of signals arising in the central nervous system, which is connected through afferent pathway receptors to the peripheral respiratory system (airways, lung, and thorax). Notwithstanding the mechanism that generates the stimulus is always the same, the sensation of dyspnea is often described with different verbal descriptors: these descriptors, or linguistic ‘clusters’, are clearly influenced by socio-individual factors related to the patient. These factors can play an important role in identifying the etiopathogenesis of the underlying cardiopulmonary disease causing dyspnea. The main goal of rehabilitation is to improve dyspnea; hence, quantifying dyspnea through specific tools (scales) is essential in order to describe the level of chronic disability and to assess eventual changes after intervention. Improvements, even if modest, are likely to determine clinically relevant changes (minimal clinically important difference, MCID) in patients.Currently there exist a large number of scales to classify andcharacterize dyspnea: the most frequently used in everydayclinical practice are the clinical scales (e.g. MRC or BDI/TDI, inwhich information is obtained directly from the patients through interview) and psychophysical scales (such as the Borg scale or VAS, which assess symptom intensity in response to a specific stimulus, e.g. exercise).It is also possible to assess the individual’s dyspnea in relationto specific situations, e.g. chronic dyspnea (with scales that classify patients according to different levels of respiratorydisability); exertional dyspnea (with tools that can measure the level of dyspnea in response to a physical stimulus); and transitional (or ‘follow up’) dyspnea (with scales that measure the effect in time of a treatment intervention, such as rehabilitation).

2010 - Non-invasive ventilation in chronic obstructive pulmonary disaese (chapter 23). In: Elliott M, Nava S, Schonhofer B. (eds) Non-inavsive Ventilation and Weaning: principles and practice. [Monografia/Trattato scientifico]
Clini, Enrico; Crisafulli, E; Ambrosino, N.
abstract

Advanced chronic obstructive pulmonary disease (COPD) is associated with peripheral and respiratory muscular weakness with nocturnal and daytime arterial blood gases abnormalities (including hypercapnia) leading to chronic respiratory failure (CRF). At present, long-term oxygen-therapy (LTOT) is the only recognized long-term treatment that has been shown to significantly improve survival in these patients. An alternative therapeutic approach proposed, especially in patients with worsening hypercapnia, is nocturnal non-invasive ventilation (NIV). The three main theories that explain the efficacy of NIV, as applied by positive pressure (NIPPV), in these patients are:opportunity for resting of fatigued respiratory muscles, improvement in thoracic-pulmonary mechanics, and the ‘resetting’ of the central respiratory drive. In contrast with the strong evidence favouring the use of NIV in acute exacerbation of COPD, many studies performed in severe but stable patients have shown inconsistent and conflicting results. In the short term, NIV has been shown to reduce the rate of hospitalization, as well as to improve both the patient’s quality of life and their functional status. However, long-term assessments did not find any effect on survival and the strongest outcomes were not affected by the use of NIPPV even when added to LTOT.Recommendations of an international consensus conference published in 1999 provided the basis for NIV prescription in stableadvanced COPD patients – nocturnal hypoventilation, sleep fragmentation and daytime arterial hypercapnia; which are stillconsidered the optimal indications for domiciliary NIV, in particular in the presence of severe-progressive deterioration of the clinical condition and instability of respiratory function.

2010 - Non-invasive ventilation in chronic obstructive pulmonary disease [Capitolo/Saggio]
Clini, E. M.; Crisafulli, E.; Ambrosino, N.
abstract

Advanced chronic obstructive pulmonary disease (COPD) is associated with peripheral and respiratory muscular weakness with nocturnal and daytime arterial blood gas abnormalities (including hypercapnia) leading to chronic respiratory failure (CRF). At present, long-term oxygen therapy (LTOT) is the only recognized long-term treatment that has been shown to significantly improve survival in these patients. An alternative therapeutic approach proposed, especially in patients with worsening hypercapnia, is nocturnal non-invasive ventilation (NIV). The three main theories that explain the efficacy of NIV, as applied by positive pressure (NIPPV), in these patients are: opportunity for resting of fatigued respiratory muscles, improvement in thoracic-pulmonary mechanics, and the ‘resetting’ of the central respiratory drive. In contrast with the strong evidence favouring the use of NIV in acute exacerbation of COPD, many studies performed in severe but stable patients have shown inconsistent and conflicting results. In the short term, NIV has been shown to reduce the rate of hospitalization, as well as to improve both the patient’s quality of life and their functional status. However, long-term assessments did not find any effect on survival and the strongest outcomes were not affected by the use of NIPPV even when added to LTOT. Recommendations of an international consensus conference published in 1999 provided the basis for NIV prescription in stable advanced COPD patients – nocturnal hypoventilation, sleep fragmentation and daytime arterial hypercapnia – which are still considered the optimal indications for domiciliary NIV, in particular in the presence of severe-progressive deterioration of the clinical condition and instability of respiratory function.

2010 - Obesity and eating disorders. Indications for the different levels of care. An italian Expert Consensus Document [Articolo su rivista]
Donini, Lm; Cuzzolaro, M; Spera, G; Badiali, M; Basso, N; Bollea, Mr; Bosello, O; Brunani, A; Busetto, L; Cairella, G; Cannella, C; Capodaglio, P; Carbonelli, Mg; Castellaneta, E; Castra, R; Clini, Enrico; Contaldo, F; Dalla Ragione, L; Dalle Grave, R; D'Andrea, F; Del Balzo, V; De Cristofaro, P; Di Flaviano, E; Fassino, S; Ferro, Am; Forestieri, P; Franzoni, E; Gentile, Mg; Giustini, A; Jacoangeli, F; Lubrano, C; Lucchin, L; Manara, F; Marangi, G; Marcelli, M; Marchesini, G; Marri, G; Marrocco, W; Melchionda, N; Mezzani, B; Migliaccio, P; Muratori, F; Nizzoli, U; Ostuzzi, R; Panzolato, G; Pasanisi, F; Persichetti, P; Petroni, Ml; Pontieri, V; Prosperi, E; Renna, C; Rovera, G; Santini, F; Saraceni, V; Savina, C; Scuderi, N; Silecchia, G; Strollo, F; Todisco, P; Tubili, C; Ugolini, G; Zamboni, M.
abstract

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

2010 - Patients’ characterization, hospital course and clinical outcomes in five Italian Respiratory Intensive Care Units [Articolo su rivista]
E., Polverino; S., Nava; M., Ferrer; P., Ceriana; Clini, Enrico; E., Spada; E., Zanotti; L., Trianni; L., Barbano; C., Fracchia; B., Balbi; M., Vitacca
abstract

Background: Respiratory intensive care units (RICU) dedicated to weaning could be suitable facilities for clinical management of “post-ICU” patients Methods: We retrospectively analyzed the time course of patients' characteristics, clinical outcomes and sanitary staff utilization in 5 Italian RICU by comparing 3 periods of 5 consecutive years (from 1991 to 2005). Results: 3,106 patients (age, 76±4 yrs; 72% males) were analyzed. The number of co-morbidities per patient (from 1.8 to 3.0, p=0.05) and the previous intensive care unit stay (from 25 to 32 days, p=0.002) increased over time. The doctor-to-patients ratio significantly decreased over time (from 1:3 to 1:5, p&lt;0.01) while the physiotherapist-to-patients ratio mildly increased (from 1:6 to 1:4.5, p&lt;0.05). The overall weaning success rate decreased (from 87% to 66%, p&lt;0.001) and the discharge destination changed (p&lt;0.001) over time; less patients were discharged to home (from 22% to 10%), and more patients to nursing home (from 3% to 6%), acute hospitals (from 6% to 10%) and rehabilitative units (from 70% to 75%). The mortality rate increased over time (from 9% to 15%). Significant correlations between the doctor-to-patients ratio and the rates of weaning success (r=0.679, p=0.005), home discharge (r=0.722, p=0.002), and the RICU length of stay (LOS) (r=-0.683, p=0.005) were observed.Conclusions: The clinical outcomes of our units worsened over 15 years, likely as consequence of admitting more severely-ill patients. The potential negative influence of reduced medical staff availability on weaning success, home discharge and LOS warrants further prospective investigations.

2010 - Sindrome da distress respiratorio acuto [Capitolo/Saggio]
M., Confalonieri; C., Torregiani; Clini, Enrico
abstract

Trattazione della fisiopatologia, clinica e intervento terapeutico razionale nelle sindromi ipossiemiche dell'adulto.

2010 - The role of pre- and post rehabilitation in lung resection surgery [Articolo su rivista]
E., Venturelli; E., Crisafulli; A., De Biase; C., Lorenzi; Clini, Enrico
abstract

Pulmonary Rehabilitation (PR) is a non-pharmacologic hospital-based multidisciplinary and comprehensive intervention aimed at reducing disability of candidates. The surgical patient may per se represent a “serious” patient to be evaluated with the scope to be included in rehabilitation. Indeed, it is clear from the clinical experience that a considerable proportion of patients undergoing thoracic surgery may have a increased risk for severe postoperative pulmonary complications and/or death. Notwithstanding, relevance of PR in special conditions such as pre-post abdominal and or thoracic surgery is not widely valuable. In this review we would like to emphasize both the rationale and the activities of a pre- or post rehabilitation program dedicated to candidates to lung resection. We deal with selection of candidates, role of rehabilitation and the most popular applied techniques in this clinical area.At present PR, which is known to hasten respiratory patients’ physical performance, may be of benefit in patients who have to undergo lung resection surgery and also may improve respiratory functions in their postoperative period. However, further research is urgent in order to consider priorities of PR application in this field.

2009 - ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy) [Articolo su rivista]
Brunelli, A; Charloux, A; Bolliger, Ct; Rocco, G; Sculier, Jp; Varela, G; Licker, Mj; Ferguson, Mk; Faivre Finn, C; Huber, Rm; Clini, Enrico; Win, T; De Ruysscher, D; Goldman, L; on behalf of the European Respiratory, Society; European Society of Thoracic Surgeons joint task force on fitness for radical, Therapy
abstract

The European Respiratory Society (ERS), in collaboration with the European Society of Thoracic Surgery (ESTS), has proposed to bring together multidisciplinary experts on functional evaluation of lung cancer patients to draw up recommendations in order to provide clinicians with clear, up-to-date guidelines on fitness for surgery and chemo-radiotherapy.The subject was divided in different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, no central literature review being performed. The draft reports written by the experts on each topic were reviewed, discussed and voted by the entire expert panel. The evidence supporting each recommendation was summarized, and graded as described by the Scottish intercollegiate Guidelines Network Grading Review Group. Clinical practice guidelines were generated and finalized in a functional algorithm for risk-stratification of the lung resection candidatesemphasizing cardiologic evaluation, systematic carbon monoxide lung diffusion capacity and exercise testing. Contrary to lung resection, for which the scientific evidences are more robust, we were unable to recommend any specific test, cut-off value, or algorithm before radio-chemotherapy due to the lack of data. We recommend that lung cancer patients should be managed in specialized settings by multidisciplinary teams.

2009 - ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy) (European Respiratory Journal (2009) 34 (17-41)) [Articolo su rivista]
Brunelli, A.; Charloux, A.; Bolliger, C. T.; Rocco, G.; Sculier, J. -P.; Varela, G.; Licker, M.; Ferguson, M. K.; Faivre-Finn, C.; Huber, R. M.; Clini, E. M.; Win, T.; De Ruysscher, D.; Goldman, L.
abstract

2009 - Effects of early inpatient rehabilitation after acute exacerbation of COPD [Articolo su rivista]
Clini, Enrico; Ernesto, Crisafulli; Costi, Stefania; Giuseppina, Rossi; Cristina, Lorenzi; Fabbri, Leonardo; Nicolino, Ambrosino
abstract

We have undertaken an observational retrospective cohort study to assess feasibility and clinical effectiveness of early rehabilitation in patients recovering from acute exacerbation of COPD (AECOPD).A cohort of 1826 inpatients (73% male, age 70±8 yrs, FEV1 50±16% pred.) admitted to a pulmonary rehabilitation (PR) program and completing at least 15 sessions were divided into categories according to their dyspnoea grade (Medical Research Council -MRC scores 2 to 5) as assessed before AECOPD. The pre-post changes in 6 minute walking distance test (6MWD), perceived end-effort dyspnoea (Borg scale), and self-reported quality of life (St George respiratory Questionnaire: SGRQ) were measured throughout. Absolute change in 6MWD (52 [95%CI 45 to 59], 65 [95%CI 60 to 70], 63 [95%CI 59 to 66], and 70 [95%CI 67 to 74] meters in MRC-2 to 5 respectively) and the percentage of patients achieving the minimal clinically important difference (MCID) of +54 m (40, 55, 57, and 61%, respectively, p=0.001) differed across MRC grades. Proportion of patients able to reach ≥350 m at the 6MWD after PR was higher in MRC 4 and 5 (18 and 22%) as compared to MRC 2 and 3 (6 and 15%). Early PR in a cohort of AECOPD patients is feasible and it is associated to clinically meaningful improvement in exercise tolerance independent on the severity of dyspnoea. The proportion of patients reaching the limit of ≥350 m after this intervention is higher in the most severe patients.

2009 - Effects of unsupported upper extremity training in patients with chronic airway obstruction: a randomized clinical trial. [Articolo su rivista]
Costi, Stefania; Ernesto, Crisafulli; Francesca Degli, Antoni; Claudio, Beneventi; Fabbri, Leonardo; Clini, Enrico
abstract

Introduction: Recent guidelines on pulmonary rehabilitation (PR) recommend upper extremity exercise training (UEET) in patients with chronic obstructive pulmonary disease (COPD). However, literature still questions the effectiveness of systematic UEET in this population.Objective: We aimed to verify the effects of unsupported UEET on functional exercise capacity, ability to perform activities of daily living (ADL) and symptoms perceived during activities involving upper extremity in COPD patients.Methods: We conducted a randomized trial comparing the effects of unsupported UEET plus PR (Intervention) to those of PR alone (Control). Change in 6-minute ring test (6MRT) was the primary outcome; ADL field test (4 shuttle stations), dyspnea score as assessed by Medical Research Council (MRC) scale, London Chest Activity of Daily Living scale (LCADL), and 6-minute walked distance (6MWT) served as secondary outcomes of the study . Results: Fifty COPD patients were consecutively randomized into the two groups and completed the study. At the end of rehabilitation period, 6MRT specifically improved in Intervention (p&lt;0.001) but not in Control group; number of rings moved at 6MRT, shuttles completed at the ADL field test, 6MWT and MRC significantly and greatly changed (p&lt;0.01) in Intervention as compared with Control group. At 6-month follow-up, rings moved at 6MRT (p=0.039) and LCADL (p=0.001) were still significantly better in Intervention as compared with Control group.Conclusion: Our trial corroborates the effectiveness of unsupported UEET in specifically improving functional exercise capacity of COPD patients. Moreover, it also provides evidence that this training modality may ameliorate and maintain the patients’ autonomy over and above standard PR.

2009 - Erratum: Subjective sleep quality during Average Volume Assured Pressure Support (AVAPS) ventilation in patients with hypercapnic COPD: A physiological pilot study (Lung (2009) 187: 5 (299-305) DOI: 10.1007/s00408-009-9167-1) [Articolo su rivista]
Crisafulli, E.; Manni, G.; Kidonias, M.; Trianni, L.; Clini, E. M.
abstract

2009 - Exercise Capacity as a Pulmonary Rehabilitation Outcome [Articolo su rivista]
Clini, Enrico; Crisafulli, E.
abstract

Disabled patients with chronic respiratory disease and peripheral skeletal muscle disorders have limitations in their exercise capacity, which may be improved after specific training in a pulmonary rehabilitation (PR) program. Individual assessment of exercise capacity by clinically available exercise tests represents an important patient-centered outcome that should be embedded in the rehabilitation process. These measurements include laboratory (treadmill and/or cycle ergometer) and field (walking) tests. The cardiopulmonary exercise test, both performed with incremental (incremental-load test) or predetermined (constant-load or endurance test) loading, is an excellent means to describe the profile of an individual's maximal exercise capacity and to record its change after PR. Among the variety of field-based tests, 6-min walking and shuttle walking are 2 simple tests widely used during PR. These tests are inexpensive and provide information on an individual's functional abilities: the 6-min walking test has been shown to provide level of disability and functional status, whereas the shuttle walking test has been shown to be more suitable to detect change of physical performance following PR. Overall, several available physiologically targeted tests are useful to measure the patient's tolerance to exercise, and many are even sensitive to change once intervention has taken place. In particular, endurance modality tests seem to provide better measurement of changes after PR than incremental exercise tests.

2009 - Home non-invasive mechanical ventilation and long-term oxygen therapy in stable hypercapnic chronic obstructive pulmonary disease patients: Comparison of costs [Articolo su rivista]
Clini, Enrico; Giovanna, Magni; Ernesto, Crisafulli; Stefano, Viaggi; Nicolino, Ambrosino
abstract

BACKGROUND: A cost analysis of nocturnal non-invasive ventilation (NNV) in stable chronic obstructive pulmonary disease (COPD) patients would be helpful in decision making, when the balance between the increased demand and the availability of resources should be checked. OBJECTIVES: Based on data from the Italian trial in stable hypercapnic COPD patients, this study compares the cost of care associated with the use of NNV when added to the usual long-term oxygen therapy (LTOT) with the cost of care of LTOT regimen alone. METHODS: Cost was calculated in 77 of 90 patients included into that trial. Analysis included drug therapy, hospitalisations due to acute exacerbation, oxygen and ventilator equipment. An estimation of charges was made according to the national sources of cost for drugs and hospital admissions and the actualised reimbursement for the home care provided to both oxygen and ventilator users. The cost/day comparison was made between the individual patients in the 2 groups (NNV + LTOT, n = 35; LTOT, n = 42). RESULTS: The mean cost of drugs and oxygen was similar in both groups, whereas the cost of hospitalisation tended to be lower in NNV + LTOT compared to LTOT alone (8.25 +/-10.29 vs. 12.50 +/- 20.28 EUR/patient/day, p &lt; 0.05). Inclusion of the ventilator equipment increased the total cost to 23.73 EUR/day in the NNV + LTOT compared to 21.42 EUR/day in the LTOT group (not significant). CONCLUSIONS: The present report suggests that long-term management with addition of non-invasive ventilation does not increase costs compared with the usual LTOT regimen: the hospital-related costs were reduced when using the ventilator in these hypercapnic COPD patients.

2009 - Long-Term Weight Loss and Maintenance in Morbidly Obese Individuals with Obstructive Sleep Apnea. (letter) [Articolo su rivista]
Clini, Enrico; Lugli, D; Prato, F; Crisafulli, E.
abstract

Non disponibile

2009 - Lung function evaluation before surgery in lung cancer patients: how are recent advances put into practice ? [Articolo su rivista]
A., Charloux; A., Brunelli; Bolliger, C. T.; G., Rocco; Sculier, J. P.; G. Varela M., Licker; Ferguson, M. K.; C., Faivre Finn; R., Huber; Clini, Enrico; T., Win; D., De Ruysscher; L., Goldman; on behalf of the European Respiratory, Society; European Society of Thoracic Surgeons Joint Task Force on Fitness for Radical, Therapy
abstract

Objective: This survey in preparation of the task force work investigated how the recent advances in pre-operative assessment of lung cancer patients have been put into practice among the European Society of Thoracic Surgeons (ESTS) and of the Thoracic Oncology Section of the European Respiratory Society (ERS). Methods: A web-based questionnaire was designed by the ERS/ESTS Task Force on Fitness for Radical Therapy in Lung Cancer Patients and sent to all members of the ESTS and of the ERS thoracic oncology section. Results: Two hundred sixty five physicians responded and 179 completely answered the questionnaire. Most of them (72%) were surgeons and worked in academic hospitals. Forty-two percent answered that the pre-op work-up is planned by a multidisciplinary team and 33% followed published recommendations. Only 30% of respondents use recommended cardiac indexes to stratify cardiac risk before lung resection. One third of participants assess DLCO in all patients although 75% think DLCO is a strong predictor of outcomes. About 80% of respondents think exercise tests have an important role in the decision to operate or not, but an integrated cardio-pulmonary exercise test is performed in only 0-30% of cases by about 80% of respondents. Exercise tests are prescribed by most physicians in patients with low predicted post-operative FEV1 or DLCO. Low-technology tests are of wide interest (only 7% never perform them) but various tests are used with various indications. Regarding patients’care management, 80% of physicians use physiotherapy before or after lung surgery and most of them assign many advantages to pulmonary rehabilitation. Eighty percent of respondents think that patients should be admitted to intensive care units after pneumonectomy. Almost 90% of participants emphasize that the ability to predict impairment of quality of life is an appropriate goal for future studies. Finally, about 70% of respondents stated that lung cancer patients should be treated only in specialized centres. Conclusions: This survey provides a snapshot of the opinion of more than 200 specialists from 38 countries regarding the management of patients with potentially resectable lung cancer. The results identify a lack of consensus in some areas as well as the difficulties of putting some recommendations into practice.

2009 - Physiotherapy of respiratory patients: An evidence-based intervention [Articolo su rivista]
Clini, E. M.; Confalonieri, M.
abstract

2009 - Short-Term Efficacy of Upper-Extremity Exercise Training in Patients With Chronic Airway Obstruction: A Systematic Review. [Articolo su rivista]
Costi, Stefania; M., Di Bari; P., Pillastrini; D'Amico, Roberto; E., Crisafulli; C., Arletti; Fabbri, Leonardo; Clini, Enrico
abstract

Background, Objectives, and Measurements Patients with chronic airway obstruction (CAO) frequently experience dyspnea and fatigue during activities performed by accessory muscles of ventilation, which competitively participate in arm elevation. This systematic review of randomized controlled trials (RCTs) concerning patients with CAO addresses the effects of upper-extremity exercise training (UEET), added to lower-extremity training or comprehensive pulmonary rehabilitation, on the following patient-centered outcomes: exercise capacity, symptoms, ability to perform daily activities, and health-related quality of life. METHODS:/b&gt; Studies were retrieved using comprehensive database and hand-search strategies. Two independent reviewers determined study eligibility based on inclusion criteria. A detailed description of treatments was mandatory. Reviewers rated study quality and extracted information on study methods, design, intervention, and results. RESULTS: /b&gt; Forty publications were evaluated. Four RCTs met the inclusion criteria but had serious methodological limitations, which introduce possible biases that reduce their internal validity. The outcomes measured were heterogeneous, and the results were inconsistent regarding maximal exercise capacity, dyspnea, and health-related quality of life. No effect of UEET was demonstrated for measures of arm fatigue. Limitations and CONCLUSIONS:/b&gt; The limited methodological quality of the studies retrieved prevented us from performing a meta-analysis, the results of which could be misleading. This systematic review shows that there is limited evidence examining UEET and that the evidence available is of poor quality. Therefore, a recommendation for the inclusion or exclusion of UEET in pulmonary rehabilitation programs for individuals with CAO is not possible. Further research is needed to definitively ascertain the effects of this training modality on patient-centered outcomes.

2009 - Subjective sleep quality during average volume assured pressure support (AVAPS) ventilation in patients with hypercapnic COPD: A physiological pilot study [Articolo su rivista]
Crisafulli, E; Manni, G; Kidonias, M; Trianni, L; Clini, Enrico
abstract

Non-invasive Positive Pressure Ventilation (NPPV) is an advanced treatment (1) aimed to improve both physiological (2-4) and clinical outcomes (5-7), including sleep (8-10), during the long-term management of patients with Chronic Respiratory Failure (CRF) due to severe hypercapnic Chronic Obstructive Pulmonary Disease (COPD). Several studies evaluating the nocturnal application of mask ventilation in stable COPD patients (11-13) have shown a limited effectiveness of pressure based modes of NPPV in this patient group. However, further studies have shown that compliance to ventilation may influence the long-term efficacy of this treatment as patients who are compliant with NPPV are able to maintain arterial blood gase (ABG) improvements over 6-months when compared with those who discontinued this therapy (14).A new NPPV modality, called Average Volume Assured Pressure Support (AVAPS), combines both the pressure and volume characteristics of ventilation and, accordingly, delivers a range of inspiratory pressures to guarantee a pre-fixed inspiratory tidal volume. This hybrid mode of ventilation has been studied in intubated patients with acute respiratory failure (15) and in patients with chronic hypoventilation linked to obesity (16,17) and other conditions (16). Under these circumstances AVAPS is able to induce high pulmonary volumes and reduce muscle workload, thus providing physiological benefits and comfort similar to those achieved by pressure support (PS) modes. However, positive effects on sleep quality have not yet been confirmed.This pilot evaluated short-term compliance, night-time efficacy and physiological responses to Average Volume Assured Pressure Support (AVAPS) ventilation in patients with stable hypercapnic COPD.

2009 - The European Respiratory Society and European Society of Thoracic Surgeons clinical guidelines for evaluating fitness for radical treatment (surgery and chemoradiotherapy) in patients with lung cancer [Articolo su rivista]
Brunelli, A; Charloux, A; Bolliger, Ct; Rocco, G; Sculier, Jp; Varela, G; Licker, Mj; Ferguson, Mk; Faivre Finn, C; Huber, Rm; Clini, Enrico; Win, T; De Ruysscher, D; Goldman, L.
abstract

The European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) established a joint task force with the purpose to develop clinical evidence-based guidelines on evaluation of fitness for radical therapy in patients with lung cancer. The following topics were discussed, and are summarized in the final report along with graded recommendations: Cardiologic evaluation before lung resection; lung function tests and exercise tests (limitations of ppoFEV1; DLCO: systematic or selective?; split function studies; exercise tests: systematic; low-tech exercise tests; cardiopulmonary (high tech) exercise tests); future trends in preoperative work-up; physiotherapy/rehabilitation and smoking cessation; scoring systems; advanced care management (ICU/HDU); quality of life in patients submitted to radical treatment; combined cancer surgery and lung volume reduction surgery; compromised parenchymal sparing resections and minimally invasive techniques: the balance between oncological radicality and functional reserve; neoadjuvant chemotherapy and complications; definitive chemo and radiotherapy: functional selection criteria and definition of risk; should surgical criteria be re-calibrated for radiotherapy?; the patient at prohibitive surgicalrisk: alternatives to surgery; who should treat thoracic patients and where these patients should be treated?

2009 - Use of functional independence measure in rehabilitation of inpatients with respiratory failure [Articolo su rivista]
Franco, Pasqua; Gian Luca, Biscione; Girolmina, Crigna; Romana, Gargano; Vittorio, Cardaci; Luigi, Ferri; Alfredo, Cesario; Clini, Enrico
abstract

Most outcomes do not deeply express the degree of disability in patients with respiratory failure (RF) following inpatient pulmonary rehabilitation (IPR). The aim of our study was to evaluate the efficacy of an IPR in patients with confirmed COPD and RF using functional independence measure (FIM) that determines the degree of disability experienced by patients and the progress they make during rehabilitation. This scale includes several items: self care, mobility, locomotion, communication and social recognition. Twenty-two patients (age 70+/-2 years, PO(2) 58.18+/-7.63mmHg, PCO(2) 46.82+/-9.11mmHg) were prospectively observed and studied. IPR included respiratory and peripheral muscle training, mucus evacuation techniques, and energy conservation techniques. FIM, Medical Research Council dyspnoea scale (MRC), St. George's Respiratory Questionnaire (SGRQ), and 6-min walking distance (6-MWD) were assessed on admission (pre) and discharge (post) from IPR. After IPR there was a statistically significant improvement (p&lt;0.01) in all the FIM items (total score in self care, mobility, locomotion, social recognition) except for communication. Changes of MRC (pre 4.32+/-0.84; post 3.00+/-1.15, p&lt;0.001), SGRQ (\%) (pre 69.86+/-4.62; post 46.50+/-11.94, p&lt;0.001), and 6-MWD (pre 164.54+/-98.63; post 214.32+/-97.64, p&lt;0.001) paralleled those improvements. An inverse correlation between MRC and FIM (r=-0.5042, p=0.016) was observed. Our preliminary study has shown that the benefits of IPR in COPD with RF do not only translate in dyspnoea, exercise capacity and quality of life but also within neuromotor disabilities as assessed by FIM. Our results warrant future studies in pulmonary rehabilitation using FIM as an outcome measure.

2008 - Activity and analysis of costs in a dedicated weaning centre. [Articolo su rivista]
Clini, Enrico; P., Siddu; L., Trianni; R., Graziosi; E., Crisafulli; M. T., Nobile
abstract

AIM: To analyse the diagnosis-related characteristics and the costs of treating patients with difficult/prolonged weaning from mechanical ventilation we have undertaken a retrospective observational study. METHODS: The study has considered all the patients admitted to our weaning unit of a regional Rehabilitation department during 3 consecutive periods since the opening date. Characteristics of the admitted patients and the DRG-related cares delivered have been recorded. A cost analysis has been obtained over time. RESULTS: The number of beds allocated to this unit (from 4 in the 1st period to 6 in the 2nd and 3rd periods) and the number of patients cared for (from 32 to 43 and to 65, respectively) increased over time. In particular, the COPD to non-COPD patient ratio (from 2.2 to 1.3 and to 1.0) and the DRG/patient weight (from 3.0 +/- 0.3 to 3.1 +/- 0.2 and to 3.3 +/- 0.2 point) changed significantly (p &lt; 0.05). The daily reimbursement per patient from the public health care system only slightly increased, whereas the operating margin (reimbursement less costs) per patient significantly improved (from -304, to +17 and +55 Euro/pt/day, respectively, p &lt; 0.05) due to a gradual restriction in the variable costs. Length of stay, mortality rate and weaning rate did not change over time. CONCLUSION: The weaning centre is a hospital area where economic burdens should be carefully evaluated. Given the actual reimbursement received on a national level for these patients, variable costs might be better spread, thus optimising the burdens without losing out on clinical outcomes.

2008 - Commencing rehabilitation in the ICU. [Articolo su rivista]
Clini, Enrico; F., Degli Antoni; Costi, Stefania; L., Trianni
abstract

Rehabilitation is an integral part of the management of patients inIntensive Care Units (ICUs).The most important aim in this area isto enhance the patient's overall functional capacity and to restorehis/her respiratory and physical independence, thus decreasing the risks of bed-rest and associated complications.The evidence for applying a weaning protocol and physiotherapytechniques (postures, percussion/vibration, limb exercise, and active mobilization) in these patients has proved to be effective according to the application rationale of each process. However, todate, there are only strong recommendations concerning the evidence-based strategies to speed weaning from mechanical ventilation.Early physiotherapy may be effective in the ICU: nonetheless,most techniques need to be further studied in a wider population.In particular, evidence supporting physiotherapy interventionsis limited as there are no studies examining the specific effectsof interventions on long-term outcomes.

2008 - Cost-effectiveness of NIV applied to chronic respiratory failure.(Chapter 26). [Monografia/Trattato scientifico]
Clini, Enrico; Crisafulli, E; Moretti, M; Fabbri, Leonardo
abstract

The expansion of HMV in the last 15 yrs was stimulated by the introduction of non-invasive mask ventilation and the recognition that more patient groups could benefit.In the management of health-care resources the costs-analysis currently represents a method to evaluate the expenditure due to the effects on health of a new (or specific) intervention and to assess it in the economic perspective. Disability-adjusted life years (DALYs), healthy year equivalents (HYEs), or quality-adjusted life years (QALYs) are all time-based measures of health that include the impact of interventions on years of life lost due to premature mortality and years of life lived with a non-fatal health outcome, weighted by the severity of that outcome.Despite effectiveness of non-invasive HMV has been addressed so far, the impact of this treatment on the overall costs is not clearly reported nor still demonstrated and very few data based on a true economic analysis in patients under non-invasive HMV are published. Direct and (partially) indirect cost calculation have been observed and reported especially in COPD patients under non-invasive HMV. The most recent data underlie the large impact of non-invasive HMV on both patients’ outcome (reduction of recurrent admissions and increase in quality of life) and families’ burden (unemployment, financial and social issues), thus prompting new studies with appropriate cost-effectiveness and/or cost-utility analysis.

2008 - Cost-effectiveness of NIV applied to chronic respiratory failure.Eur [Capitolo/Saggio]
Clini, Enrico; E., Crisafulli; M., Moretti; Fabbri, Leonardo
abstract

The expansion of home mechanical ventilation (HMV) in the last 15 yrs was stimulated by the introduction of noninvasive mask ventilation and the recognition that more patient groups could benefit.In the management of healthcare resources, cost-analysis currently represents a method for evaluation of the expenditure due to the effects on health of a new (or specific) intervention and for assessing it in the economic perspective. Disabilityadjustedlife-yrs, healthy-yr equivalents and quality-adjusted life-yrs are all time-based measures of health that include the impact of interventions on years of life lost due to premature mortality and years of life lived with a nonfatal health outcome, weightedby the severity of that outcome.Although the effectiveness of noninvasive HMV has been addressed, the impact of this treatment on the overall costs has not been clearly reported or demonstrated and very few data based on a true economic analysis in patients under noninvasive HMV have been published. Direct and (partially) indirect cost calculations have been observed and reported, especially in chronic obstructive pulmonary disease patients under noninvasive HMV. The most recent data underline the large impact ofnoninvasive HMV on both patient outcome (reduction of recurrent admissions and increase in quality of life) and family burden (unemployment, financial and social issues), thus prompting further studies with appropriate cost-effectiveness and/or cost-utility analysis.

2008 - Home-centred physical fitness programme in morbidly obese individuals: a randomized controlled trial [Articolo su rivista]
Riccardo, Tumiati; Gianni, Mazzoni; Ernesto, Crisafulli; Barbara, Serri; Claudio, Beneventi; Cristina M., Lorenzi; Giovanni, Grazzi; Francesco, Prato; Francesco, Conconi; Fabbri, Leonardo; Clini, Enrico
abstract

OBJECTIVE: To assess the effectiveness of domiciliary physical fitness programmes in obese individuals. DESIGN: Nine-month randomized controlled trial. SETTING: Home-based intervention with outpatient visits. SUBJECTS: Morbidly obese subjects (body mass index (BMI) > or = 30) aged 25-65 years suitable for physical activities at home. INTERVENTION: At the end of a preliminary one-month in-hospital rehabilitation programme (baseline), 52 patients were randomly assigned either to a structured educational programme (intervention group) of daily incremental physical activity at home (walking and skeletal muscle resistance training, with booklets and written instructions) or to a programme of general advice (control group) regarding exercise and long-term fitness. MAIN MEASURES: Both groups were evaluated at baseline and every three months for: (1) time, metabolic equivalents (METs), and heart rate reserve (HRR) during a standardized 2-km walking test (2kmWT); (2) anthropometric measures (body weight, BMI, abdominal and neck circumference); (3) the Polar Fitness Test index (PFTI), and (4) time to exhaustion while sustaining consecutive isoload extensions in the dominant leg (isoload LE). Time during 2kmWT was the study primary outcome. RESULTS: Body weight, BMI and abdominal circumference improved significantly (P < 0.05) over time in the intervention group. The cardiopulmonary fitness variables changed significantly (P < 0.05) over time in both study groups. However, all variables improved in the intervention patients, while some worsened or remained stable in the controls. Thus, the mean group difference in changes was significant (P < 0.05) for 2kmWT time (-77.4 seconds), HRR (11.7\%), and PFTI (5.4 points). CONCLUSION: This structured domiciliary fitness programme is feasible and provides sustained anthropometric and physiological benefits in some morbidly obese individuals.

2008 - ICU acquired neuropathy and myopathy [Articolo su rivista]
Clini, E. M.; Crisafulli, E.; Trianni, L.
abstract

Patients admitted to intensive care often develop complications. Among these, acquired difficulties with neuromuscular function are widely recognised as potential causes of clinical worsening and delayed recovery in these individuals. Critical Illness Pofineuropathy and Critical Illness Myopathy are the most commonly recognised disorders which often occur simultaneously in the critically ill patients. Incidence of both Critical Illness Polineuropathy (from 2 to 80%) and Critical Illness Myopathy (from 1 to 7%) vary consistently according to the patients' selection, being diagnosis mainly addressed by clinical signs and electromyography test. Awareness among health care professionals, early recognition and diagnosis, patient's education about outcome and long-term prognosis, streamlining rehabilitation perspectives are considered short- and long-term key aspects which may optimise care in these patients. This short review will provide the main aspects dealing with definitions, epidemiology, risk factors, and clinical management of acquired difficulties with neuromuscular function in the critical care area.

2008 - Indications and Physiological Basis of Rehabilitation in the ICU [Capitolo/Saggio]
Clini, E. M.; Ambrosino, N.
abstract

2008 - Indications and physiological basis of rehabilitation in ICU [Capitolo/Saggio]
Clini, Enrico; Ambrosino, N.
abstract

Description of new approach to early physiotherapy in severy ill patients admitted to intensive care areas.

2008 - Indications and physiological basis of rehabilitation in ICU. (Chapter 9) [Capitolo/Saggio]
Clini, Enrico; N., Ambrosino
abstract

Not available

2008 - Nonpharmacological treatment and relief of symptoms in COPD. [Articolo su rivista]
Clini, Enrico; N., Ambrosino
abstract

Evidence-based guidelines for chronic obstructive pulmonary disease (COPD) have recently been developed. Nonpharmacological treatments have evolved rapidly as an essential part of COPD therapy. They are especially important as complementary interventions in severe or very severe disease, when there is loss in function, a reduction in quality of life and when psychological impairments further complicate the disease. The present article discusses the most used nonpharmacological treatments for severe COPD patients (rehabilitation, long-term oxygen therapy, surgery, noninvasive positive pressure ventilation and supportive nutrition) and their evidence-based usefulness in promoting strategies that relieve symptoms. All of these interventions are used during end-stage disease, to promote self-efficacy, relieve symptoms and prevent further deterioration. These therapeutic options support physicians and allied professionals in improving symptom management for their patients.

2008 - Nutrition in the ICU [Capitolo/Saggio]
Clini, Enrico; L., Trianni; N., Ambrosino
abstract

Description of nutritional support techniques in critically ill individuals. Long-term strategies to implement nutrition at home in chronically ventilated individuals

2008 - Predictors of 6-month mortality in elderly patients with mild chronic obstructive pulmonary disease discharged from a medical ward after acute nonacidotic exacerbation. [Articolo su rivista]
Piera, Ranieri; Angelo, Bianchetti; Alessandro, Margiotta; Adriana, Virgillo; Clini, Enrico; Marco, Trabucchi
abstract

OBJECTIVES: To identify clinical outcomes and variables associated with 6-month mortality in very elderly patients admitted for nonacidotic acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Prospective cohort study. SETTING: General medicine acute care ward. PARTICIPANTS: Two hundred forty-four elderly patients with COPD (mean age+/-standard deviation 82+/-7, 55.7\% female) admitted to the hospital because of non-acidotic AECOPD. MEASUREMENTS: Cognitive and mood status and physiological variables were measured. Self-reported comorbidities were assessed using the Charlson Comorbidity Index. In-hospital and long-term mortality and clinical outcomes were recorded. RESULTS: At admission, this elderly population with AECOPD had low cognitive performance (mean Mini-Mental State Examination score 21+/-5), no presence of significant depressive symptoms (Geriatric Depression Scale score 4+/-3), good nutritional status (body mass index (BMI) 25.1+/-5.5), moderate comorbidity (Charlson Comorbidity Index 4.0+/-1.9), high functional disability (Barthel Index (BI) 52+/-34), and moderate severity of acute exacerbation (Acute Physiology and Chronic Health Evaluation (APACHE) II score 9.7+/-4.2). Two hundred twenty-five inpatients with AECOPD were successfully discharged, whereas 15 were transferred to the intensive care unit, and four died in the hospital. The 6-month cumulative mortality rate in discharged patients with AECOPD was 20\%. Multivariate Cox analysis shows that lower BMI (beta=-0.16; 95\% confidence interval (CI)=0.73-0.99), higher APACHE II score (beta=0,17; 95\% CI=1.03-1.36), and lower BI at discharge (beta=-0.02; 95\% CI=0.96-0.99) were independently associated with 6-month mortality. CONCLUSION: Malnutrition, severity of exacerbation and disability status could be identified as risk factors associated with 6-month mortality of elderly patients admitted for nonacidotic AECOPD.

2008 - Rehabilitation in patients submitted to lung resection surgery: A retrospective analysis [Articolo su rivista]
Crisafulli, E.; Venturelli, E.; De Biase, A.; Righi, D.; Rizzardi, R.; Lorenzi, C.; Fabbri, L. M.; Clini, E. M.
abstract

Background and aim. Several diseases may affect the thoraco-pulmonary system. In most cases resection surgery represents the elective therapy. To date, consensus is still lacking on the efficacy of post-surgery rehabilitation (PR) in these patients. Aim of our study was, therefore, to evaluate the effectiveness of a PR in patients undergoing thoraco-polmonary resection surgery. Patients and measurements. Forty patients referred for PR "Villa Pineta" Hospital-Rehabilitation Centre (in the period January 2006 to December 2007) after thoraco-pulmonary resection surgery were studied; 24 out of them had been directly transferred from the Surgery Unit (Early Rehabilitation), while other 16 came from their home with surgery having taken place at least 15 days before (Late Rehabilitation). The following outcome measures were recorded at baseline and at the end of PR: respiratory muscle performance (MIP and MEP), arterial blood gases (ABG - PaO2, PaCO2, pH, SatO2, PaO2/FiO2), the distance walked at the 6 minute test (6MWD) with related symptoms (dispnoea and muscle fatigue), scale of chronic dispnoea (MRC), questionnaire of perceived quality of life (SGRQ). Results. After PR, significant improvements (p &lt;0.05) related to MIP-MEP, 6MWD with symptoms, MRC and SGRQ have been recorded in both subgroups. Only patients in the Early Rehabilitation group also showed improvements of blood oxygenation (PaO2, SatO2, PaO2/FiO2). Univariate analysis performed among groups in all the outcomes taking number and percentage of patients improved (as assessed by a pre-defined cut-off), has shown that both dyspnea (p =0.014) and muscle fatigue (p = 0.046) significantly differ in favour of the Early rehabilitation group. Conclusions. Our study suggests that rehabilitation may produce clinically relevant improvements in patients recovering from thoraco-pulmonary resection surgery. Effectiveness is more likely to be higher if program is applied early after surgery.

2008 - Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation [Articolo su rivista]
Crisafulli, E; Costi, Stefania; Luppi, Fabrizio; Cirelli, G; Cilione, C; Coletti, O; Fabbri, Leonardo; Clini, Enrico
abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often associated with other chronic diseases. These patients are often admitted to hospital based rehabilitation programmes. OBJECTIVES: To determine the prevalence of chronic comorbidities in patients with COPD undergoing pulmonary rehabilitation and to assess their influence on outcome. DESIGN: Observational retrospective cohort study. SETTING: A single rehabilitation centre. PATIENTS: 2962 inpatients and outpatients with COPD (73\% male, aged 71 (SD 8) years, forced expiratory volume in 1 s (FEV(1)) 49.3 (SD 14.8)\% of predicted), graded 0, 1 or &gt;/=2 according to the comorbidity categories and included in a pulmonary rehabilitation programme. Measurements: The authors analysed the number of self-reported comorbidities and recorded the Charlson Index. They then calculated the percentage of patients with a predefined positive response to pulmonary rehabilitation (minimum clinically important difference (MCID)), as measured by improvement in exercise tolerance (6 min walking distance test (6MWD)), dyspnoea (Medical Research Council scale) and/or health related quality of life (St George's Respiratory Questionnaire (SGRQ)). RESULTS: 51\% of the patients reported at least one chronic comorbidity added to COPD. Metabolic (systemic hypertension, diabetes and/or dyslipidaemia) and heart diseases (chronic heart failure and/or coronary heart disease) were the most frequently reported comorbid combinations (61\% and 24\%, respectively) among the overall diseases associated with COPD. The prevalence of patients with MCID was different across the comorbidity categories and outcomes. In a multiple categorical logistic regression model, the Charlson Index (OR 0.72 (96\% CI 0.54 to 0.98) and 0.51 (96\% CI 0.38 to 0.68) vs 6MWD and SGRQ, respectively), metabolic diseases (OR 0.57 (96\% CI 0.49 to 0.67) vs 6MWD) and heart diseases (OR 0.67 (96\% CI 0.55 to 0.83) vs SGRQ) reduced the probability to improve outcomes of rehabilitation. CONCLUSIONS: Most patients with COPD undergoing pulmonary rehabilitation have one or more comorbidities. Despite the fact that the presence of comorbidities does not preclude access to rehabilitation, the improvement in exercise tolerance and quality of life after rehabilitation may be reduced depending on the comorbidity.

2008 - Role of hyperinflation vs. deflation on dyspnoea in severely to extremely obese subjects. [Articolo su rivista]
I., Romagnoli; P., Laveneziana; Clini, Enrico; P., Palange; G., Valli; F., de Blasio; F., Gigliotti; G., Scano
abstract

AIM: To test the hypothesis that obese individuals may either hyperinflate or deflate the lung when exercising. In both cases breathlessness is an inescapable consequence. METHODS: Ventilatory variables, end-expiratory lung volume and end-inspiratory lung volume, and dyspnoea score (Borg scale) were studied in 20 class II-III obese subjects and 14 healthy controls during incremental symptom-limited cycle exercise. RESULTS: Ventilation increased with increasing work rate, in obese and in control subjects; most obese subjects had to increase end-expiratory lung volume to escape from flow limitation; in contrast, like controls, a few subjects deflated the lung on heavy-to-peak exercise. Dyspnoea was equal in degree at anaerobic threshold and peak exercise in obese as in control subjects, and in obese who hyperinflated as in those who deflated the lung. In particular, end-expiratory lung volume at baseline (r = -0.84, P = 0.04) was negatively correlated with changes in Borg score in obese who did not hyperinflate: the lower the former the higher the latter. On the other hand, tidal volume (r = 0.54, P = 0.045) and decrease in inspiratory reserve volume (r = 0.59, P = 0.028) were positively correlated with the Borg score in obese subjects who hyperinflated. No other independent variable correlated with the Borg score. CONCLUSIONS: We conclude that not all obese subjects had to increase end-expiratory lung volume on heavy-to-peak exercise. Changes in dyspnoea for unit changes in ventilation were similar in obese who did hyperinflate as well as in those who did not, suggesting that the increase in respiratory neural drive, associated with an increase in ventilation, is an important source of dyspnoea in obese as well as in control subjects.

2007 - Effectiveness of erdosteine in elderly patients with bronchiectasis and hypersecretion: A 15-day, prospective, parallel, open-label, pilot study [Articolo su rivista]
Ernesto, Crisafulli; Orietta, Coletti; Costi, Stefania; Emanuela, Zanasi; Cristina, Lorenzi; Sasa, Lucic; Fabbri, Leonardo; Marco, Bertini; Clini, Enrico
abstract

BACKGROUND: Mucus plugging and hypersecretion have been associated with an increased relative risk of death in patients with bronchiectasis who may or may not have chronic obstructive pulmonary disease (COPD), which is of prognostic relevance in the elderly. However, chest physiotherapy and/or the use of mucoactive agents is considered to be an effective therapeutic model in treating patients with COPD and bronchiectasis. OBJECTIVE: The objective of this study was to test the effectiveness of oral erdosteine in treating elderly patients with bronchiectasis and chronic mucus hypersecretion who have been referred to a pulmonary rehabilitation program. METHODS: In this 15-day, prospective, parallel, open label, pilot study, elderly patients with bronchiectasis, hypersecretion, a noncurrent smoking status, who had been consecutively enrolled at Ospedale Villa Pineta's Pulmonary Rehabilitation Center, Pavullo-Modena, Italy, were randomized into 2 treatment groups. Group 1 consisted of those patients receiving PO erdosteine 225 mg BID and chest physiotherapy; group 2 comprised those patients receiving chest physiotherapy alone. Forced lung volumes, arterial blood gases, respiratory muscle strength, walking capacity (as measured by 6-minute walking test [6MWT]), and visual analog scale (VAS) symptoms (cough and dyspnea) were recorded at enrollment and at the conclusion of the study. Mucus density (MD), mucus purulence (MP), and mucus volume produced (MVP) were assessed using a 3-point scale (0 = best or low; 1 = moderate; and 2 = worst or high) at baseline and at 5-day time points during the study period. All measurements were assessed by personnel blinded and not directly associated with the study administration. RESULTS: Thirty patients (21 [70%] male and 9 [30%] female; mean [SD] age, 71 [11] years; and mean [SD] weight, 66 [3] kg) were enrolled. Characteristics were similar in the 2 groups at baseline. At day 15, significant improvements were observed in 6MWT, VAS cough, and VAS dyspnea (P &lt; 0.01) in both groups. However, a significant improvement in forced expiratory volume in 1 second and forced vital capacity (in milliliters) was observed only in group i (0.2 [0.3]; P &lt; 0.05). At day 15, improvement was observed in mean (SD) in MD, MP, and MVP scores for both groups. Significant changes, however, were observed in all 3 measurements in group 1 (-0.80 [0.22], -0.71 [0.51], and 1.01 [0.39], respectively), whereas a significant improvement was observed only in MD (-0.55 [0.44]) and MVP (0.45 [0.62]) in group 2. The improvement in MVP observed in group 1 was significantly better than that observed in group 2 (P &lt; 0.05). CONCLUSION: This pilot study found that a regimen of PO erdosteine 225 mg BID in addition to routine chest physiotherapy provided some physiologic and clinical benefits in the treatment of these elderly patients with bronchiectasis and chronic mucus hyper-secretion.

2007 - Effects of a walking aid in COPD patients receiving oxygen therapy [Articolo su rivista]
E., Crisafulli; Costi, Stefania; F., DE BLASIO; G., Biscione; F., Americi; S., Penza; E., Eutropio; F., Pasqua; Fabbri, Leonardo; Clini, Enrico
abstract

STUDY OBJECTIVES: To elucidate whether a simple walking aid may improve physical performance in COPD patients with chronic respiratory insufficiency who usually carry their own heavy oxygen canister. DESIGN: Randomized crossover trial. SETTING: Physiopathology laboratory of three rehabilitation centers. PATIENTS AND INTERVENTIONS: We studied 60 stable COPD patients (mean age, 70.6 +/- 7.9 years; FEV(1), 44.8 +/- 14.3% of predicted [+/- SD]) with chronic respiratory insufficiency who randomly performed, on 2 consecutive days, a standardized 6-min walking test using two different modalities: a full-weight oxygen canister transported using a small wheeled cart and pulled by the patient (Aid modality) or full-weight oxygen canister carried on the patient's shoulder (No-Aid modality). MEASUREMENTS AND RESULTS: The distance walked, peak effort dyspnea, and leg fatigue scores as primary outcomes, and other cardiorespiratory parameters as secondary outcomes were recorded during both tests. A significant difference (p &lt; 0.05) between the two tests occurred for all the measured outcomes in favor of the Aid modality. Most importantly, significant changes for distance (+ 43 m, p &lt; 0.001), peak effort dyspnea (- 2.0 points, p &lt; 0.001), leg fatigue (- 1.4 points, p &lt; 0.001), as well as for mean and nadir oxygen saturation and heart rate with the Aid modality (but not with the No-Aid modality) were recorded in the subgroup of patients walking &lt; 300 m at baseline. CONCLUSIONS: This study suggests that a simple walking aid may be helpful in COPD patients receiving long-term oxygen therapy, particularly in those with lower residual exercise capacity.

2007 - Higher than expected rest hypoxemia in a 74-year old COPD patient with only mild airway obstruction. [Capitolo/Saggio]
Clini, Enrico; A., D'Armini; I., Sampablo
abstract

Not available

2007 - Higher than expected rest hypoxemia in a 74-year old COPD patient with only mild airway obstruction. [Monografia/Trattato scientifico]
Clini, Enrico; D’Armini, M; Sampablo IIn: Donner, Cf; Carone M., Clinical Challanges in COPD
abstract

Descrizione di un caso clinico di paziente con leve compromissione della funzione polmonare e alterazione grave degli scambi respiratori imputabile a trombosi delle arterie polmonari

2007 - La Riabilitazione Respiratoria. [Monografia/Trattato scientifico]
Clini, Enrico; Ambrosino, N.
abstract

Trattato aggiornato sul razionale e la applicazione delle metodologie cliniche riabilitative nell'ambito delel patologie respiratorie a evoluzione disabilitante.

2007 - Multidisciplinary rehabilitation project in a disabled patient receiving mechanical ventilation [Articolo su rivista]
Antoni, F. D.; Beneventi, C.; Trianni, L.; Lorenzi, M. C.; Clini, E. M.
abstract

Pulmonary rehabilitation is a multidisciplinary non-pharmacological therapy delivered to patients with disability following respiratory chronic disorders or even post-acute respiratory consequences. The present description reports a case of rehabilitation process applied to a patient following cardio-surgery with respiratory insufficiency as a major complication. This case report shows an example of the professional integration and of the sharing process of rehabilitation. This is individually tailored and aimed at improving the patient's individual abilities and perceived quality of life.

2007 - Post-operative respiratory rehabilitation after lung resection for non-small cell lung cancer [Articolo su rivista]
Alfredo, Cesario; Luigi, Ferri; Domenico, Galetta; Franco, Pasqua; Stefano, Bonassi; Clini, Enrico; Gianluca, Biscione; Vittorio, Cardaci; Stefania di, Toro; Alessia, Zarzana; Stefano, Margaritora; Alessio, Piraino; Patrizia, Russo; Silvia, Sterzi; Pierluigi, Granone
abstract

BACKGROUND: To investigate the efficacy of an inpatient Pulmonary Rehabilitation program (i-PR) after lung resection (LR) for Non-Small Cell Lung Cancer (NSCLC). PATIENTS AND METHODS: From January 2001 to December 2004, 211 out of 618 patients who underwent LR were considered eligible for i-PR. Twenty-five patients accepted the i-PR and were included in the case group. The remaining 186 who refused i-PR were taken as controls. RESULTS: The two study groups were comparable for demographic and surgical characteristics, as well as for the peri-operative morbidity (4\% in the controls and 3\% among patients undergoing i-PR). Most functional parameters among treated patients were improved when baseline versus 1-month figures were compared, despite the strong correction for multiple comparison limited statistical significance to Borg scale dyspnoea on exertion - median - (2 versus 0; p<0.01); pH (7.45 versus 7.42; p<0.05); timed walk-6MWD (297.8m versus 393.4m; p<0.01) and Hb saturation during 6MWD (95.4\% versus 93.9\%; p<0.05). On the contrary, global function in the group of controls was homogeneously decreased (FEV(1) and PEF p<0.01) after operation. The comparison of treated and untreated patients 1 month after the operation did not show any significant difference in terms of FEV(1), FVC, PEF, distance, Hb saturation, and KCO that instead were homogeneously and significantly worse at baseline (before the surgical operation) in the case group. CONCLUSIONS: Respiratory Function and exercise capacity significantly improve following a post-operative 4-week i-PR in lung resected patients. i-PR could be regarded as a component of the management of patients who have undergone LR for cancer.

2007 - Recommendations for pulmonary rehabilitation [Articolo su rivista]
Pasqua, F.; Garuti, G.; Sabato, E.; Clini, E. M.; Ambrosio, N.
abstract

2007 - Respiratory muscles training in COPD patients [Articolo su rivista]
Ernesto, Crisafulli; Costi, Stefania; Fabbri, Leonardo; Clini, Enrico
abstract

It is known that respiratory muscles undergo adaptation in response to overload stimuli during exercise training in stable COPD patients, thus resulting in significant increase of respiratory muscle function as well as the individual's improvements. The present article reviews the most updated evidence with regard to the use of respiratory muscle training (RMT) methods in COPD patients. Basically, three types of RMT (resistive training, pressure threshold loading, and normocapnic hyperpnea) have been reported. Frequency, duration, and intensity of exercise must be carefully considered for a training effect. In contrast with the plentitude of existing data inherent to inspiratory muscle training (IMT), literature is still lacking in showing clinical and physiological studies related to expiratory muscle training (EMT). In particular, while it seems that IMT is slightly superior to EMT in providing additional benefits other than respiratory muscle function such as a reduction in dyspnea, both the effects and the safety of EMT is still to be definitively elucidated in patients with COPD.

2007 - Six-minute walk test in patients with chronic obstructive pulmonary disease: Comparison with and without active coaching [Articolo su rivista]
Crisafulli, E.; Lorenzi, M. C.; Gherardini, G.; Eutropio, E.; Beneventi, C.; Fabbri, L. M.; Clini, E. M.
abstract

Aim. To assess the sk-minute walk test (6 MWT) with and without encouragement in patients with severe chronic obstructive pulmonary disease (COPD). Methods. Thirty-eight COPD patients (72 ± 6 years, FEV 37 ± 12% pred.) performed 6 MWT in random order in two non consecutive days. The first test was carried out including encouragement according to the ATS standard procedure (WTE), the second without any phrase of encouragement (WTNE). Subgroup analysis has been also performed by dividing patients on the basis of their own level of exercise tolerance at the baseline test (6 MWT &lt; 300 and &gt; 300 meters). The measured variables included the total distance covered (M), subjective dyspnoea (D) and leg fatigue (F) as assessed by Borg scale, the main cardio-respiratory parameters as recorded along the test. Results. M was significantly higher during WTE than during WTNE (370 ± 78 and 336 ± 79 meters, respectively), whereas D and F only showed a non significant trend to increase during WTE. No significant differences of the other physiological parameters have been recorded between the two tests. Results similar to those obtained in the whole group have also been observed in both pre-defined subgroups of patients. Conclusions. Our study has shown that the encouraged recommended modality of 6 MWT is associated to a better result in terms of walked distance as compared with the non encouraged test in severe COPD patients. This was not associated with a detrimental effect on the cardiopulmonary responses.

2006 - Capitolo 14 "Valutazione delle attività della vita quotidiana" [Capitolo/Saggio]
Costi, Stefania; Cristina Lorenzi, Maria; Clini, Enrico
abstract

2006 - Esame clinico in Riabilitazione Respiratoria. [Capitolo/Saggio]
Lazzeri, M; Arlati, S; Clini, E.
abstract

2006 - Esame clinico in Riabilitazione Respiratoria. [Monografia/Trattato scientifico]
Lazzeri, M; Clini, Enrico; Repossini, E; Corrado, A.
abstract

Trattato aggiornato sulle le valutazioni e le misure di outcome all'interno dei programmi di riabilitazione dedicati ai pazienti con patologie respiratorie a evoluzione disabilitante.

2006 - Inspiratory muscle training: a way to breathe more easily [Articolo su rivista]
Clini, Enrico; Costi, Stefania
abstract

nd

2006 - Interdisciplinary rehabilitation in morbidly obese subjects: an observational pilot study. [Articolo su rivista]
Clini, Enrico; F., Prato; M., Nobile; M., Bondi; B., Serri; C., Cilione; D., Lugli
abstract

BACKGROUND AND AIM: To assess the clinical effectiveness of a interdisciplinary rehabilitation programme (CR), in a population of morbidly obese subjects we have undertaken a observational study. METHODS: The study included fifty-nine adult subjects (18 M, 60+/-10 years, BMI 47+/-8) with sleep-disturbance related symptoms and disabilities. Assessment and correction of sleep disordered breathing (SDB) abnormalities, improvement of exercise tolerance, body weight and associated psychological features were the aims of this CR, which has been carried out over a 1 month period.Lung functions, apnea/hypopnea index (AHI), 6-minute walking distance (6MWD), body weight (BW), quality of life by means of Sat-P questionnaire and serum metabolic data has been recorded at baseline (TO), at the end (Ti) and 6 months after (T2) the CR. RESULTS: The percentage of patients with AHI &gt; 10 declined from 65% (at TO) to 20% (at both T1 and T2). 6MWD and BW significantly improved (p &lt; 0.005) at T1 and still maintained at T2; a significant relationship (r = 0.379, p &lt; 0.01) has been found between changes of BW and 6MWD recorded in between TO and T2. Sat-P item scores dealing with sleep efficiency, problem solving, and social interactions improved (p &lt; 0.01) at T1 and still maintained at T2. CONCLUSIONS: This hospital-based CR provides indication for effectiveness in advanced morbidly obese subjects and warrants further controlled trials to confirm the results.

2006 - Intrapulmonary percussive ventilation in tracheostomized patients: A randomized controlled trial [Articolo su rivista]
Clini, Enrico; F., Degli Antoni; M., Vitacca; E., Crisafulli; M., Paneroni; S., Chezzi Silva; M., Moretti; L., Trianni; Fabbri, Leonardo
abstract

OBJECTIVE: To investigate whether the addition of intrapulmonary percussive ventilation to the usual chest physiotherapy improves gas exchange and lung mechanics in tracheostomized patients. DESIGN AND SETTING: Randomized multicenter trial in two weaning centers in northern Italy. PATIENTS AND PARTICIPANTS: 46 tracheostomized patients (age 70 +/- 7 years, 28 men, arterial blood pH 7.436 +/- 0.06, PaO(2)/FIO(2) 238 +/- 46) weaned from mechanical ventilation. INTERVENTIONS: Patients were assigned to two treatment groups performing chest physiotherapy (control), or percussive ventilation (IMP2 Breas, Sweden) 10 min twice/day in addition to chest physiotherapy (intervention). MEASUREMENTS AND RESULTS: Arterial blood gases, PaO(2)/FIO(2) ratio, and maximal expiratory pressure were assessed every 5th day for 15 day. Treatment complications that showed up in 1 month of follow-up were recorded. At 15 days the intervention group had a significantly better PaO(2)/FIO(2) ratio and higher maximal expiratory pressure; after follow-up this group also had a lower incidence of pneumonia. CONCLUSIONS: The addition of percussive ventilation to the usual chest physiotherapy regimen in tracheostomized patients improves gas exchange and expiratory muscle performance and reduces the incidence of pneumonia.

2006 - Maximal inspiratory and expiratory pressure measurement in tracheotomised patients [Articolo su rivista]
M., Vitacca; M., Paneroni; L., Bianchi; Clini, Enrico; A., Vianello; P., Ceriana; L., Barbano; B., Balbi; S., Nava
abstract

The present study compared four different sites and conditions for the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) in 38 spontaneous breathing tracheotomised patients. Of the patients, 28 had chronic obstructive pulmonary disease (COPD). The four different conditions were: 1) through a cuff inflated cannula (condition A); 2) through the mouth with a deflated cannula (condition B); 3) through the mouth with a phonetic uncuffed cannula (condition C); and 4) through the mouth after stoma closure (condition D). Five trials in each condition were performed using a standardised method. The measurement of both MIP and MEP differed significantly depending on the condition of measurement. MIP taken in condition A was significantly higher when compared with conditions B, C and D. MEP in condition A was significantly higher when compared with condition B and D. In condition A the highest frequency of the best measurement of MIP and MEP was observed at the fourth and fifth effort, respectively. The same results were obtained after the selection of only COPD patients. In conclusion, respiratory muscle assessment differs significantly depending on measurement condition. Measurement through inflated cannula tracheotomy yields higher values of both maximal inspiratory and maximal expiratory pressure.

2006 - Repeated pulmonary rehabilitation in severe and disabled COPD patients [Articolo su rivista]
Micaela, Romagnoli; Daniela, Dell'Orso; Cristina, Lorenzi; Ernesto, Crisafulli; Costi, Stefania; Daniela, Lugli; Clini, Enrico
abstract

BACKGROUND: The optimal frequency of delivering a pulmonary rehabilitation program (PR) is not yet a well established issue. It is still unclear whether repeated PR at established intervals will result in effective maintenance or further improvement in the patient's health status. OBJECTIVES: To investigate whether more frequently repeated PR in patients with COPD (1) leads to similar short and long-term physiological gains, and (2) decreases the burden due to hospitalization. METHODS: Thirty-five disabled COPD patients (FEV(1) below 50\% predicted, MRC score 3) in a stable state were studied in a randomized controlled trial. After completing an initial inpatient PR program, they were randomly assigned to either group 1 (performing a second and a third PR after 6 and 12 months) or group 2 (performing only a second PR after 12 months). RESULTS: Lung functions, exercise capacity (by means of a timed walk test - 6MWT), peak-effort dyspnea (D) and leg fatigue (F), and health-related quality of life by means of SGRQ were assessed prior to (T1, T3, T5) and after (T2, T4, T6) each PR program: the same measures were taken on an outpatient basis at T3 in group 2. The number of hospital admissions (HA) and days spent in the hospital (DH) were also recorded over the year. The two groups did not differ in any parameter at baseline. 6MWD, D, F and SGRQ improved to the same level (p = 0.05) after each PR in both groups. However, the baseline level of D, F and SGRQ symptoms and impact scores progressively improved over time in group 1 but not in group 2. After 12 months, a larger amount of patients in Group 1, as compared to Group 2, reported H10 DH/year (p &lt; 0.0001). CONCLUSIONS: In severe and disabled COPD, a more frequently repeated inpatient PR may lead to some additional physiological and clinical benefits over 1 year.

2006 - Update in pulmonary rehabilitation. [Articolo su rivista]
Costi, Stefania; Crisafulli, E; FABBRI L., M; Clini, Enrico
abstract

nd

2005 - Early physiotherapy in the respiratory intensive care unit [Articolo su rivista]
Clini, Enrico; Nicolino, Ambrosino
abstract

Physiotherapy is an integral part of the management of patients in respiratory intensive care units (RICUs). The most important aim in this area is to enhance the overall patient's functional capacity and to restore his/her respiratory and physical independence, thus decreasing the risks of bed rest associated complications. This article is a review of evidence-based effectiveness of weaning practices and physiotherapy treatment for patients with respiratory insufficiency in a RICU. Literature searches were performed using general and specialty databases with appropriate keywords. The evidence for applying a weaning process and physiotherapy techniques in these patients has been described according to their individual rationale and efficacy. The growing number of patients treated in RICUs all over the world makes this non pharmacological approach both welcome and interesting. However, to date, there are only strong recommendations concerning the evidence-based strategies to speed weaning. Early physiotherapy may be effective in ICU: however, most techniques (postures, limb exercise and percussion/vibration in particular) need to be further studied in a large population. Evidence supporting physiotherapy intervention is limited as there are no studies examining the specific effects of interventions on long-term outcome.

2005 - Inpatient pulmonary rehabilitation: does it make sense? [Articolo su rivista]
Clini, Enrico; M., Romagnoli
abstract

Among the nonpharmacological therapies, pulmonary rehabilitation (PR) is particularly appropriate for patients with chronic respiratory impairment who, despite any optimal drug management, are still symptomatic and experience restriction in every day activities. Pulmonary rehabilitation performed in inpatient, outpatient, or home settings demonstrates short- and long-term clinical efficacy. Although disease severity does not inherently dictate candidacy for exercise training, the degree of physiological and functional impairment may influence setting in which the training should occur. Therefore, inpatient rehabilitation is generally best-suited for the most sick and most disabled patients. The overall results from the literature confirm that the inpatient setting for a PR program is a feasible option and does not necessarily result in higher direct costs when balanced against duration and effectiveness in terms of improved outcomes.

2005 - Length and clinical effectiveness of pulmonary rehabilitation in outpatients with chronic airway obstruction [Articolo su rivista]
Rossi, G; Florini, F; Romagnoli, M; Bellantone, T; Lucic, S; Lugli, D; Clini, Enrico
abstract

Study objective: To assess the clinical effectiveness of pulmonary rehabilitation (PR) after 10 or 20 consecutive sessions in outpatients with chronic airway obstruction (CAO). Design: Observational prospective cohort trial. Setting: Outpatient clinic of a rehabilitation center. Patients and interventions: Twenty-five outpatients (mean age, 65 +/- 9 years [+/- SD]; FEV1, 64 +/- 12% predicted) admitted to a comprehensive PR program, including exercise training. Measurements and results: The load reached on a cycloergometer (maximal achieved load [W-max]), the maximal and isoload dyspnea and leg fatigue on a Borg scale, 6-min walk distance (6MWD), and the health-related quality of life as assessed using the St. George's Respiratory Questionnaire (SGRQ) [total and components score] have been recorded as outcome measures at baseline, after 10 sessions (T10), and after 20 sessions (T20). The predefined criteria of the clinically significant improvement were as follows: + 15% W-max, + 54 m at 6MWD, - 1 point at isoload dyspnea and leg fatigue, and - 4% at SGRQ scores. There was a mean significant difference between changes at T20 and T10 for 6MWD (- 42.96 m; 95% confidence interval [0], - 57.79 to - 28.12 m; p = 0.001), total SGRQ (4.80; 95% CI, 2.29 to 7.31; p = 0.001), activity SGRQ (3.60; 95% CI, 0.48 to 6.71; p = 0.025), and symptoms SGRQ (5.96; 95% CI, 2.72 to 9.2; p = 0.001). The percentage of patients who improved was different at T20 as compared with T 10 for W-max (68% and 48%, respectively; p = 0.025), 6MWD (76% and 20%, p = 0.001), and total SGRQ (64% and 36%, p = 0.008). Conclusions: A 10-session course of PR provides only limited clinically significant changes of outcome measures when compared with a 20-session course in outpatients with CAO of mild-to-moderate severity.

2005 - Supported arm training in patients recently weaned from mechanical ventilation [Articolo su rivista]
Roberto, Porta; Michele, Vitacca; Lucia Sonia, Gilè; Clini, Enrico; Luca, Bianchi; Ercole, Zanotti; Nicolino, Ambrosino
abstract

STUDY OBJECTIVES: To evaluate the effects of early exercise training in patients recovering from acute respiratory failure needing mechanical ventilation (MV). DESIGN: Prospective, randomized, and controlled study. SETTING: Three respiratory intermediate ICUs (RIICUs). PATIENTS: Of 228 patients admitted to an RIICU, 66 patients weaned from MV from > 48 to < 96 h were considered eligible and enrolled in the study. INTERVENTION: Sixty-six patients were randomized to either supported arm exercise training plus general physiotherapy (gPT) [group 1, 32 patients] or to gPT alone (group 2, 34 patients). MEASUREMENTS AND RESULTS: Twenty-five patients in each group completed the protocol. Group 1 showed a greater improvement in exercise capacity, as assessed by an arm incremental test (IT) [p = 0.003] and an endurance test (ET) [p = 0.021], compared to group 2. Posttraining maximal inspiratory pressure (MIP) significantly improved in both groups (p < 0.001 and p = 0.003 in groups 1 and 2 respectively; not significant). IT isoworkload dyspnea improved significantly in both groups (p = 0.005 and p = 0.009 in groups 1 and 2, respectively; not significant between groups), whereas IT isoworkload peripheral muscle fatigue (p < 0.001), ET isotime dyspnea (p < 0.01), and ET isotime muscular fatigue (p < 0.005) improved significantly in group 1 but not in group 2. IT improvers (chi2 = 0.004) and ET improvers (chi2 = 0.047) were more frequently observed in group 1 than in group 2. Baseline MIP could discriminate for IT (p = 0.013; odds ratio [OR], 1.116) and ET improvers (p = 0.022; OR, 1.067). CONCLUSION: Early upper-limb exercise training is feasible in RIICU patients recently weaned from MV and can enhance the effects of gPT. Baseline inspiratory muscle function is related to exercise capacity improvement.

2005 - Upper arm exercise in COPD patients: From physiology to bed-side [Articolo su rivista]
Brogi, S.; Lazzeri, M.; Turchetti, A.; Bisciaio, R.; Quadrelli, P.; Clini, E.
abstract

Patients suffering from COPD often complain limited activity in everyday life due to the weakness of muscles of their upper limbs, which are also involved to sustain ventilatory function. Functional mechanisms and interactions involving activated muscles of the upper limbs may lead to ventilatory asynchronism, reduced mechanical efficacy of the arms, increased load on the ventilatory pump. To date, there is evidence that specifically training the upper limb muscles may prove rationale in COPD patients. Aim of the present review is, therefore, to update the knowledge of methods and results of upper limb training in these patients. In each section of the article, data on physiology of the upper limb muscles in healthy and COPD patients as well as the effectiveness of training programs are reviewed. Methods of evaluation and modality to deliver training are also included.

2004 - Assessment of physiologic variables and subjective comfort under different levels of pressure support ventilation [Articolo su rivista]
Michele, Vitacca; Luca, Bianchi; Ercole, Zanotti; Andrea, Vianello; Luca, Barbano; Roberto, Porta; Clini, Enrico
abstract

STUDY OBJECTIVES: To evaluate the effects of 12 ventilator settings (pressure support ventilation [PSV] plus positive end-expiratory pressure [PEEP], 30 + 0 cm H(2)O; 25 + 5 cm H(2)O; 25 + 0 cm H(2)O; 20 + 5 cm H(2)O; 20 + 0 cm H(2)O; 15 + 5 cm H(2)O; 15 + 0 cm H(2)O; 10 + 5 cm H(2)O; 10 + 0 cm H(2)O; 5 + 5 cm H(2)O; 5 + 0 cm H(2)O; and 0 + 5 cm H(2)O) on physiologic variables; the percentage of ineffective efforts; patient comfort; and whether the diagnosis of COPD may influence results. DESIGN: Prospective, randomized, physiologic study. SETTING: Three weaning centers. PATIENTS: Thirty-six consecutive patients (20 patients with COPD). INTERVENTION: Patients were randomly submitted to the 12 settings. MEASUREMENTS AND RESULTS: Breathing pattern, respiratory drive (p0.1), arterial oxygen saturation (Sato(2)), heart rate, percentage of ineffective efforts per minute, patient comfort measured by means of a visual analogue scale (VAS), and BORG scale were recorded under each setting. Under different levels of assistance, breathing pattern, Sato(2), and p0.1 significantly and linearly changed (p < 0.0001) while VAS and BORG scale presented a significant (p = 0.027) U-shaped trend; high or low assistance caused the most discomfort. Under high levels of assistance, a higher (analysis of variance, p = 0.023) frequency of ineffective effort percentage was observed in the subgroup of 26 patients who presented this phenomenon. Breathing pattern significantly (p = 0.013) changed when compared to PSV alone (PSV plus zero end-expiratory pressure [ZEEP]) at the same total inspiratory pressure assistance (PSV plus PEEP). A huge variability among patients in breathing pattern and comfort was found under the setting rated as the most comfortable by patients. The diagnosis of COPD did not influence the overall results. CONCLUSIONS: The following conclusions are made: (1) physiologic variables followed a linear trend, while comfort followed a U-shaped trend under different levels of PSV (irrespective of COPD diagnosis); (2) high assistance caused an increase in ineffective efforts; (3) only the breathing pattern significantly changed when total assistance was given as PSV plus PEEP when compared to PSV alone (PSV plus ZEEP); and (4) the extreme levels of PSV are not associated with the best comfort.

2004 - Effects of Respiratory Therapist-Directed Protocol on Prescription and Outcomes of Pulmonary Rehabilitation in COPD Inpatients [Articolo su rivista]
Tramacere, A; Rizzardi, R; Cilione, C; Serri, B; Florini, F; Lorenzi, C; Clini, Enrico
abstract

BACKGROUND: The use of respiratory therapist-directed (RD) protocols in non-ICU hospitalized patients decreases respiratory care charges as compared with physician-directed (PD) protocols. OBJECTIVES: To determine whether RD or PD protocol assessments in COPD patients may impact: (1) prescription of respiratory treatments, and (2) outcomes of pulmonary rehabilitation program (PRP). METHODS: In a retrospective observational case-control study, 73 cases (RD) were compared with controls (PD) matched for age, sex, FEV1 and diagnosis of either chronic airflow obstruction (CAO), pulmonary emphysema (PE) or chronic respiratory insufficiency (CRI). PRP programs were specifically tailored and assessed for inpatients with moderate to severe COPD. Type of PRP protocol (P), number of respiratory treatments (RT), number of exercise training prescription (EXP) and failure (EXF), time to start PRP (T) and length of hospital stay (LOS) were recorded. Perceived breathlessness (B) as assessed by MRC scale, 6-min walk meters (6MWD), and BORG-dyspnea at rest (D-rest) and end of effort (D-effort) were also assessed as outcome measures before (T0) and after (T1) the PRP. RESULTS: Frequency distribution of P, EXP and EXF was similar in the two groups. However, prescription of additional RT (1.9 +/- 0.8 and 2.5 +/- 1.1 days, p<0.01), T (1.2 +/- 0.4 and 1.8 +/- 1.2 days, p<0.001) and LOS (17.2 +/- 2.0 and 18.2 +/- 1.8 days, p<0.05) were lower in cases than in controls. Both cases and controls similarly improved (p<0.0001) B, 6MWD, D-rest and D-effort at T1. CONCLUSIONS: RT-directed assessment results in less respiratory treatments prescription than PD-directed protocol and it does not affect the outcomes of in-hospital pulmonary rehabilitation of COPD patients.

2004 - Fixed airflow limitation caused by COPD or Asthma: from definition to management [Articolo su rivista]
Romagnoli, M; Clini, Enrico; Fabbri, Lm
abstract

Patients with fixed airflow limitation are often classified as chronic obstructive pulmonary disease (COPD), and some international guidelines recommend classifying asthma with fixed airflow limitation as COPD. Indeed, both COPD (induced by smoking or other noxious agents) and asthma may be associated with a decline of lung function that should cause fixed airflow limitation. In the presence of fixed airflow limitation, patients are often diagnosed COPD, even if the differential diagnosis between asthma and COPD in these patients may be important as the natural history as well as the response to treatment are different, depending on whether fixed airflow limitation is due to asthma or COPD. The assessment of patients presenting with fixed airflow limitation has recently hightlighted that airway inflammation is markedly different in asthma and COPD although characterized by the same degree of airflow limitation. Thus, asthma with fixed airflow limitation maintain the same pathological characteristics as asthma with completely reversible airflow limitation. In conclusion, subjects with asthma have distinct characteristics compared with subjects with COPD. Despite the presence of fixed airflow limitation both patients should be properly identified and treated.

2004 - Inspiratory muscle workload due to dynamic intrinsic PEEP in stable COPD patients: effects of two different settings of non-invasive pressure-support ventilation. [Articolo su rivista]
M., Vitacca; B., Lanini; S., Nava; L., Barbano; R., Porta; Clini, Enrico; N., Ambrosino
abstract

BACKGROUND: In severe stable hypercapnic COPD patients the amount of pressure time product (PTP) spent to counterbalance their dynamic intrinsic positive end expiratory pressure (PEEPi,dyn) is high: no data are available on the best setting of non invasive pressure support ventilation (NPSV) to reduce the inspiratory muscle workload due to PEEPi,dyn. METHODS: The objectives of this randomised controlled physiological study were: 1. To measure the inspiratory muscle workload due to PEEPi,dyn 2. To measure the effects on this parameter of two settings of NPSV in stable COPD patients with chronic hypercapnia admitted in a Pulmonary Division of two Rehabilitation Centers. Twenty-three stable COPD patients with chronic hypercapnia on domiciliary nocturnal NPSV for 30 +/- 20 months were submitted to an evaluation of breathing pattern, PEEPi,dyn, inspiratory muscle workload and its partitioning during both assisted and unassisted ventilation. Two settings of NPSV were randomly applied for 30 minutes each: i- "at patient's comfort" (C): Inspiratory pressure support (IPS) was the maximal tolerated pressure able to reduce awake PaCO2 with the addition of a pre-set level of external PEEP (PEEPe); ii- "physiological setting" (PH): the level of IPS able to achieve a &gt; 40% and &lt; 90% decrease in transdiaphragmatic pressure in comparison to spontaneous breathing (SB). A PEEPe level able to reduce PEEPi,dyn by at least 50% was added. RESULTS: During SB the tidal diaphragmatic pressure-time product (PTPdi/b) was 17.62 +/- 7.22 cmH2O*sec, the component due to PEEPi,dyn (PTPdiPEEPi,dyn) being 38 +/- 17% (range: 16-65%). Compared to SB,PTPdiPEEPi,dyn was reduced significantly with both settings, the reduction being greater with PH compared to C. CONCLUSIONS: In conclusion in severe COPD patients with chronic hypercapnia the inspiratory muscle workload due to PEEPidyn is high and is reduced by NPSV at a greater extent when ventilator setting is tailored to patient's mechanics.

2004 - Long-term mechanical ventilation and nutrition [Articolo su rivista]
Ambrosino, N; Clini, Enrico
abstract

Mechanical ventilation (MV) in chronic situations is commonly used, either delivered invasively or by means of non-invasive interfaces, to control hypoventilation in patients with chest wall, neuromuscular or obstructive lung diseases (either in adulthood or childhood). The global prevalence of ventilator-assisted individuals (VAI) in Europe ranges from 2 to 30 per 100000 population according to different countries. Nutrition is a common problem to face with in patients with chronic respiratory diseases: nonetheless, it is a key component in the long-term management of underweight COPD patients whose muscular disfunction may rapidly turn to peripheral muscle waste. Since long-term mechanical ventilation (LTMV) is usually prescribed in end-stage respiratory diseases with poor nutritional status, nutrition and dietary intake related problems need to be carefully assessed and corrected in these patients. This paper aims to review the most recent innovations in the field of nutritional status and food intake-related problems of VAI (both in adulthood and in childhood).

2004 - Occupational therapy and pulmonary rehabilitation of disabled COPD patients [Articolo su rivista]
Cristina M., Lorenzi; Carmela, Cilione; Roberta, Rizzardi; Vittoria, Furino; Tommasina, Bellantone; Daniela, Lugli; Clini, Enrico
abstract

BACKGROUND: Occupational therapy (OT) has been defined as a task of rehabilitation for disabled patients, giving them maximal function and independence to sustain specific activities of daily living. OBJECTIVES: To evaluate the effectiveness of OT as an adjunctive measuring during pulmonary rehabilitation (PR) of hospitalized COPD patients. METHODS: A prospective clinical trial with parallel groups was undertaken in severely disabled COPD patients (n = 71, age 73 +/- 5 years). They were assigned to either OT+PR (n = 47, FEV1 46 +/- 21\%pred.) or PR (n = 24, FEV1 44 +/- 12\%pred.). PR consisted of eighteen 3-hour daily sessions, whilst OT (domestic activities) was added 3 times a week up to nine 1-hour sessions. Six-min walk (6MWD) with evaluation of BORG dyspnea (D) and leg fatigue (F) scores at end of effort, breathlessness sensation (B) by means of the MRC scale as well as the number of functions lost in the Basic Activity of Daily Living (BADL) categories were assessed as outcomes before (T0) and after (T1) rehabilitation. RESULTS: 6MWD (from 165 +/- 63 to 233 +/- 66 and from 187 +/- 52 to 234 +/- 65 m in the OT+PR and PR groups, respectively), D (from 4.9 +/- 2.1 to 3.2 +/- 1.6 and from 5.3 +/- 2.1 to 3.4 +/- 2.1), F (from 6.1 +/- 0.5 to 4.5 +/- 1.7 and from 5.9 +/- 0.8 to 4.3 +/- 0.8) and B (from 4.3 +/- 0.9 to 3.0 +/- 0.9 and from 4.2 +/- 1.0 to 3.2 +/- 0.8) had similarly improved (p < 0.01) in both groups at T1. The percentage distribution of patients across the BADL categories significantly changed (p = 0.004) in OT+PR (from 17 to 61\%, from 70 to 34\% and from 23 to 5\% in categories A, B and C, respectively) but not in the PR group. CONCLUSIONS: The addition of OT to comprehensive PR is able to specifically improve the outcome of severely disabled COPD inpatients.

2004 - Physiotherapy in the critical care area. [Articolo su rivista]
Clini, Enrico; Ambrosino, N.
abstract

nd

2004 - Rehabilitation of COPD patients: which training modality? [Articolo su rivista]
Clini, Enrico; Costi, Stefania; M., Romagnoli; F., Florini
abstract

Non pharmacological therapy has been gaining more interest and has been evolving rapidly over the last decade as an essential part of therapy for COPD patients. Pulmonary Rehabilitation (PR), the most important non pharmacological treatment in patients with COPD, has a primary goal: to achieve the highest possible level of individual exercise tolerance, thus reducing the primary and/or secondary health care utilisation. The aim of the present review is to focus the role of exercise training in these patients as well as to address the question on which training methods are the most beneficial. We have therefore undertaken a MEDLINE-based search including the terms: pulmonary rehabilitation, exercise, lung disease/obstructive. Several strategies based on endurance or strength training are nowadays implemented during PR programmes in order to maximise the benefits for each patient. The impaired function of ambulation muscles causing breathlessness as one of the more frequent symptoms in many COPD, suggests that training the lower extremities is the most important goal to achieve during pulmonary rehabilitation of these patients. On the other hand, as muscle strength appears to be an independent contributor to survival and utilisation of health care resources, it seems largely justified also to include this further modality in the PR program of these patients. In conclusion, both modalities are effective and useful for COPD patients. However, whether resistance training should be administered to all COPD and which is the optimal length of strength training still needs to be elucidated.

2004 - Water / electrolyte imbalances in AECOPD. [Capitolo/Saggio]
Moretti, M; Clini, Enrico; Fabbri, Lm
abstract

Not available

2004 - Water / electrolyte imbalances in AECOPD. In: Siafakas N, Anthonisen NR, Georgopoulos D. (eds) Acute exacerbations of Chronic Obstrutive Pulmonary Disease. [Monografia/Trattato scientifico]
Moretti, M; Clini, Enrico; Fabbri, Leonardo
abstract

Water and electrolyte imbalance occuring in AECOPD suggests a complex interactions between pulmonary haemodynamics, acid-base balance, hormonal and renal mechanisms. Further studies are required 1) to investigate the contribution of different mechanisms in oedema formation , 2) to select COPD patients at risk of developing chronic right ventricular failure, and 3) to define more effective therapeutical approaches in preventing oedema formation.

2003 - Hospital monitoring, setting and training for home non invasive ventilation. [Articolo su rivista]
D., Fiorenza; M., Vitacca; Clini, Enrico
abstract

Although in recent years guidelines have been published in order to define indications, applications and delivery of long-term home non invasive mechanical ventilation (HNMV), there is lack of information with regards to in-hospital assessment, planning and training to initiate and prescribe it. Discontinuation and lack of compliance versus HNMV may affect the follow-up of these patients adding a costly burden for care. The present review proposes an operative flow chart for optimisation of HNMV prescription from initial patient's selection to post discharge follow up including; 1. assessment of the correct choice of ventilator, interfaces, ventilation setting. 2. Timing for different physiological monitoring (arterial gases, mechanics, sleep) 3. Timing for clinical evaluation, machine adaptation, carer training and long term follow-up.

2003 - Impact of comprehensive pulmonary rehabilitation on anxiety and depression in hospitalized COPD patients. [Articolo su rivista]
G., Garuti; C., Cilione; D., Dell'Orso; P., Gorini; M. C., Lorenzi; L., Totaro; G., Cirelli; Clini, Enrico
abstract

To prospectively evaluate the effect of inpatient pulmonary rehabilitation (iPR) on anxiety and depression as outcome measures in patients with COPD, we studied 149 consecutive adults COPD referred to our iPR after an exacerbation. Patients were divided according to the GOLD staging into: Group 1 (stage 2a, n = 48, FEV1 63 +/- 9% pred.), Group 2 (stage 2b, n = 53, FEV1 42 +/- 6% pred.) and Group 3 (stage 3, n = 48, FEV1 25 +/- 7% pred.). The iPR consisted of twelve 3-hours daily sessions. Hospital Anxiety Depression (HAD) Scale as well as 6-minute walk (6MWD) with evaluation of dyspnea (D) and leg fatigue (F) at rest and end of effort, and health related quality of life by means of St. George Respiratory Questionnaire (SGRQ) were assessed before (T0) and after (T1) the iPR. 6MWD, D and F at end of effort and SGRQ total score similarly improved (p &lt; 0.001) in all groups after iPR. The mean level of HAD-anxiety (from 9.1 +/- 4.0 to 7.7 +/- 3.5, from 9.0 +/- 4.6 to 7.2 +/- 4.6 and from 8.1 +/- 4.1 to 6.7 +/- 4.3 in group 1,2 and 3 respectively) and HAD-depression (from 9.4 +/- 3.5 to 8.2 +/- 3.5, from 9.1 +/- 4.2 to 8.2 +/- 4.5 and from 9.0 +/- 4.0 to 7.4 +/- 4.5 respectively) similarly changed (p &lt; 0.0001) over time in all groups. The total percentage of patients with abnormal score (&gt; 10) of HAD-anxiety (from 31% to 21%) and HAD-depression (from 30% to 22%) significantly decreased (p &lt; 0.05) after the iPR. Inpatient pulmonary rehabilitation may improve levels of anxiety and depression as well as symptoms, exercise capacity and health related quality of life in moderate to severe COPD patients after an acute exacerbation.

2003 - Non-pharmacological treatment for chronic obstructive pulmonary disease. [Articolo su rivista]
Clini, Enrico; Costi, Stefania; Silvano, Lodi; Giuseppina, Rossi
abstract

Evidence-based guidelines on treatment of patients with Chronic Obstructive Pulmonary Disease (COPD) have recently been developed. Non-pharmacological therapy of COPD has been receiving more interest and has been evolving rapidly in the last decade as an essential part of COPD treatment. In fact, non-pharmacological treatment is a complementary approach mainly in the advanced stages of COPD. Most of these care options appear to benefit patients in terms of quality of life and cost-effectiveness. The aim of the present review is to survey the most important non-pharmacological treatments for COPD (smoking cessation, rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation, and surgery) and their usefulness based on the currently available evidence. This review is based on an evaluation of the literature using a multimethod approach. A computerized MEDLINE search from 1966 through June 2003 was undertaken using the search terms pulmonary rehabilitation, surgery, smoking cessation, respiratory insufficiency/failure, and lung disease/obstructive. Non pharmacological treatment of COPD is a real option to successfully treat these patients and prevent further deterioration. All the included therapies are based on actual scientific evidence for patient benefits. To date, smoking cessation, comprehensive rehabilitation and long-term oxygen therapy are widely accepted as therapies which may positively impact the long-term management of COPD patients.

2003 - Noninvasive ventilation in stable chronic obstructive pulmonary.(letter) [Articolo su rivista]
Kohnlein, T; Welte, T; Clini, Enrico; Ambrosino, N.
abstract

Non disponibile

2002 - Erratum: "The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients" (Europian Respiratory Journal (2002) vol. 20 (529-538)) [Articolo su rivista]
Clini, E.; Sturani, C.; Rossi, A.; Viaggi, S.; Corrado, A.; Donner, C. F.; Ambrosino, N.
abstract

2002 - Exhaled nitric oxide and exercise tolerance in severe COPD patients. [Articolo su rivista]
Clini, Enrico; L., Bianchi; K., Foglio; M., Vitacca; N., Ambrosino
abstract

Study objective: To evaluate exhaled nitric oxide (eNO) during exercise in stable COPD patients.Setting: Outpatients' evaluation in a rehabilitation center.Patients: Eleven consecutive stable male COPD patients (age 65±6 years, FEV1 56±10% pred). Eight healthy (6 male; age: 51±16 years) non-smoking, non-atopic volunteers served as controls.Methods: In each subject a symptom-limited cycloergometry was carried out by monitoring eNO with the tidal-breath method to assess eNO concentration (FENO) and output ( NO ) at rest, peak exercise and recovery time.Results: Resting FENO (9.8±5.1 and 14.1±6.3 ppb respectively) and NO (4.2±2.0 and 5.9±3.4 nM*min-1 respectively) were lower though non significantly in COPD than in controls. In both groups FENO significantly decreased whereas NO significantly increased during exercise. Both parameters returned to baseline during the recovery time. Peak exercise NO but not FENO was significantly lower in COPD than in controls (7.9±5.4 and 12.7±6.0 nM*min-1 respectively, p<0.05). The rise in VNO was weakly correlated to O2 both in controls (R=0.31, p=0.002) and in COPD patients (R=0.22, p=0.03). FENO showed an inverse correlation to O2 in both groups (R= -0.53, p=0.000; R= -0.31, p=0.003 in controls and COPD respectively). Conclusions: In mild and moderate COPD patients eNO during exercise parallels that observed in normal controls. Exhaled NO output but not concentration is significantly reduced at peak exercise in COPD as compared to controls. The long-term effects of exercise training on eNo has to be evaluated by further studies.

2002 - Exhaled nitric oxide in chronic obstructive pulmonary disease. [Articolo su rivista]
CLINI, Enrico; AMBROSINO N., ON BEHALF OF INOC
abstract

Non disponibile

2002 - Focus on nitric oxide. [Monografia/Trattato scientifico]
Baraldi, E; Clini, Enrico; Cremona, G; IL PENSIERO SCIENTIFICO, VIGNOLA M. E. D. S.
abstract

Trattato aggiornato sulla metodica della misura dell'ossido nitrico (NO) nell'aria esalata. Definizione dei profili caratteristici in corso di varie patologie dell'apparato respiratorio.

2002 - Nitric oxide and pulmonary circulation. [Articolo su rivista]
Clini, Enrico; Nicolino, Ambrosino; on behalf of, I. N. O. C.
abstract

The aim of this review is to outline the characteristics of the pulmonary circulation in healthy and disease status and the power of exhaled NO (eNO) as a means to assess the involvement of pulmonary circulation in pathological conditions.The discovery of the endocrine role of the endothelium has generated a great interest in its potential regulatory role on the vascular tone of the pulmonary vascular bed. Nitric oxide (NO) mediated-endothelium-dependent relaxation has been demonstrated in pulmonary arteries of animals and humans. The changes in the NO pathway with pulmonary hypertension are not clear. As a matter of fact NO is important in modulating the response to acute hypoxia and the responses to increased flow and to shear stress. The amount of exhaled NO (eNO) of different species may be easily measured reflecting overall NO metabolism from the lung (thus including epithelial, endothelial and other cells activities). The development of pulmonary hypertension secondary to systemic (systemic sclerosis, chronic heart failure) or pulmonary (COPD) diseases appears to be associated with a decrease in eNO production both at rest or during exercise. Chronic inhalation of NO appears to protect against pulmonary hypertension in animal settings.Exhaled NO is growing in interest for its in vivo ability to represent the feature of pulmonary circulation in the pathological condition.

2002 - Predictors of change in exercise capacity after comprehensive COPD inpatient rehabilitation. [Articolo su rivista]
Carmela, Cilione; Cristina, Lorenzi; Daniela Dell, Orso; Giancarlo, Garuti; Giuseppina, Rossi; Lina, Totaro; Clini, Enrico
abstract

BACKGROUND: In order to evaluate the factors associated with change in exercise capacity after comprehensive inpatient Pulmonary Rehabilitation (IPR) we studied 132 consecutive adults with Chronic Obstructive Pulmonary Disease (COPD) recovering from an acute exacerbation. MATERIAL/METHODS: Lung function, arterial blood gases, and respiratory muscle strength were measured at baseline. Perceived breathlessness (B), 6-minute walk distance (6MWD), dyspnea at rest and post-exertion (D), hospital anxiety and depression (HAD), and health-related quality of life were assessed before (T0) and after (T1) IPR. The patients were divided into two groups depending on the change in 6MWD: Improvers (IM at least +54 meters after IPR, n=81) or Non-Improvers (NIM, less than 54 meters or no change, n=51). RESULTS: At T1 61\% of the patients showed improvement as here defined. The IM group showed lower 6MWD and higher B and resting-D at T0 than NIM (p<0.05). A stepwise multiple regression analysis was performed using 6MWD change as the dependent variable. and anthropometric and physiological measures at T0 as the independent variables. This regression model explained 26\% of the 6MWD-change; 6MWD and PaO2 significantly contributed to this model. CONCLUSIONS: In COPD patients recovering from an acute exacerbation, the predicted change in exercise capacity using anthropometric, demographic, clinical, and physiological variables after 2 weeks of comprehensive IPR is likely to be low. The baseline level of exercise performance and arterial oxygenation show the most consistent correlation with change in walking ability in these patients.

2002 - The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients [Articolo su rivista]
Clini, Enrico; C., Sturani; A., Rossi; S., Viaggi; A., Corrado; C. F., Donner; N., Ambrosino; Rehabilitation, ; Italian Association of Hospital, Pneumology
abstract

Chronic obstructive pulmonary disease (COPD) patients with chronic ventilatory failure (CVF) are more likely to develop exacerbations, which are an important determinant of health-related quality of life (HRQL). Long-term noninvasive positive-pressure ventilation (NPPV) has been proposed in addition to long-term oxygen therapy (LTOT) to treat CVF but little information is available on its effects on HRQL and resource consumption. Therefore, the current authors undertook a 2-yr multicentric, prospective, randomised, controlled trial to assess the effect of NPPV+ LTOT on: 1) severity of hypercapnia; 2) use of healthcare resources, and 3) HRQL, in comparison with LTOT alone. One hundred and twenty-two stable hypercapnic COPD patients on LTOT for &gt; or = 6 months were consecutively enrolled. After inclusion and 1-month run-in, 90 patients were randomly assigned to NPPV+LTOT (n=43) or to LTOT alone (n=47). Arterial blood gases, hospital and intensive care unit (ICU) admissions, total hospital and ICU length of stay and HRQL were primary outcome measures; survival and drop-out rates, symptoms (dyspnoea and sleep quality) and exercise tolerance were secondary outcome measures. Follow-up was performed at 3-month intervals up to 2 yrs. Lung function, inspiratory muscle function, exercise tolerance and sleep quality score did not change over time in either group. By contrast the carbon dioxide tension in arterial blood on usual oxygen, resting dyspnoea and HRQL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire, changed differently over time in the two groups in favour of NPPV+LTOT. Hospital admissions were not different between groups during the follow-up. Nevertheless, overall hospital admissions showed a different trend to change in the NPPV+LTOT (decreasing by 45\%) as compared with the LTOT group (increasing by 27\%) when comparing the follow-up with the follow-back periods. ICU stay decreased over time by 75\% and 20\% in the NPPV+LTOT and LTOT groups, respectively. Survival was similar. Compared with long-term oxygen therapy alone, the addition of noninvasive positive-pressure ventilation to long-term oxygen therapy in stable chronic obstructive pulmonary disease patients with chronic ventilatory failure: 1) slightly decreased the trend to carbon dioxide retention in patients receiving oxygen at home and 2) improved dyspnoea and health-related quality of life. The results of this study show some significant benefits with the use of nocturnal, home noninvasive positive-pressure ventilation in patients with chronic ventilatory failure due to advanced chronic obstructive pulmonary disease patients. Further work is required to evaluate the effect of noninvasive positive-pressure ventilation on reducing the frequency and severity of chronic obstructive pulmonary disease exacerbation.

2001 - A molecule across centuries. [Articolo su rivista]
Clini, Enrico; N., Ambrosino
abstract

Non disponibile

2001 - Comparison of two methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15 days [Articolo su rivista]
M., Vitacca; A., Vianello; D., Colombo; Clini, Enrico; R., Porta; L., Bianchi; G., Arcaro; G., Vitale; E., Guffanti; A., Lo Coco; N., Ambrosino
abstract

We designed a prospective multicenter randomized controlled study in three long-term weaning units (LWU) to evaluate which protocol, inspiratory pressure support ventilation (PSV) or spontaneous breathing trials (SB), is more effective in weaning patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in both groups). No significant difference was found in weaning success rate (73\% versus 77\% in the PSV and SB group, respectively), mortality rate (11.5\% versus 7.6\%), duration of ventilatory assistance (181 +/- 161 versus 130 +/- 106 h), LWU (33 +/- 12 versus 35 +/- 19 d), or total hospital stay. The results of these defined protocols were retrospectively compared with an "uncontrolled clinical practice" in weaning historical control patients. The overall 30-d weaning success rate was significantly greater (87\% versus 70\%) and the time spent under mechanical ventilation by survived and weaned patients was shorter in the patients in the study than in historical control patients (103 +/- 144 versus 170 +/- 127 h). The LWU and hospital stays were also significantly shorter (27 +/- 12 versus 38 +/- 18 and 38 +/- 17 versus 47 +/- 18 d). Spontaneous breathing trials and decreasing levels of PSV are equally effective in difficult-to-wean patients with COPD. The application of a well-defined protocol, independent of the mode used, may result in better outcomes than uncontrolled clinical practice.

2001 - Effect of pulmonary rehabilitation on exhaled nitric oxide in patients with chronic obstructive pulmonary disease. [Articolo su rivista]
Clini, Enrico; L., Bianchi; K., Foglio; R., Porta; M., Vitacca; N., Ambrosino
abstract

BACKGROUND: In patients with mild to moderate chronic obstructive pulmonary disease (COPD) the exercise induced increase in exhaled nitric oxide (eNO) parallels that observed in normal untrained subjects. There is no information on the effects of the level of exercise tolerance on eNO in these patients. The aim of this study was to evaluate the effect of a pulmonary rehabilitation programme including exercise training on eNO in patients with COPD. METHODS: In 14 consecutive male patients with stable COPD of mean (SD) age 64 (9) years and forced expiratory volume in one second (FEV1) 55 (14)\% predicted, fractional eNO concentration (FeNO), peak work rate (Wpeak) and oxygen uptake (VO2peak) were assessed at baseline (T-1), at the end of a 1 month run in period (T0), and after an 8 week outpatient multidisciplinary pulmonary rehabilitation programme (T1) including cycloergometer training. RESULTS: FeNO did not significantly differ at T-1 and T0 (mean (SE) 4.3 (0.6) and 4.4 (0.6) ppb, respectively), whereas it rose significantly at T1 to 6.4 (0.7) ppb (p<0.02). Compared with T0, both Wpeak and VO2 were significantly (p<0.05) increased at T1 (mean (SE) Wpeak from 89 (5.6) W to 109 (6.9) W); VO2peak from 1.27 (0.1) l/min to 1.48 (0.1) l/min). A significant correlation was found between baseline FEV1 and the change in FeNO following the rehabilitation programme (r=-0.71; p<0.05) and between changes in FeNO and Wpeak from T0 to T1(r=0.60; p<0.05). CONCLUSIONS: Pulmonary rehabilitation in patients with mild to moderate COPD is associated with an increase in exhaled nitric oxide.

2001 - Erratum: Exhaled nitric oxide in patients with PiZZ phenotype-related αI-anti-trypsin deficiency (Respiratory Medicine (2001) vol. 95 (520-525)) [Articolo su rivista]
Malerba, M.; Clini, E.; Cremonia, G.; Radaeli, A.; Bianchi, L.; Corda, L.; Pini, L.; Ricciardolo, F.; Grassi, V.; Ambrosino, N.
abstract

2001 - Exhaled nitric oxide in COPD patients. [Articolo su rivista]
Clini, Enrico; L., Bianchi; N., Ambrosino
abstract

nd

2001 - Exhaled nitric oxide in patients with PiZZ phenotype-related alpha1-anti-trypsin deficiency. [Articolo su rivista]
M., Malerba; Clini, Enrico; G., Cremona; A., Radaeli; L., Bianchi; L., Corda; L., Pini; F., Ricciardolo; V., Grassi; N., Ambrosino; F., Ricclardolo
abstract

There is no report of exhaled NO (eNO) in subjects with different phenotypes of alpha1-anti-trypsin (AAT) deficiency. Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFE(NO)]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n = 25; PiSZ n = 6; PiZZ, n = 9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20 FEV1) was also assessed. plFE(NO) was significantly lower in the PiZZ group (4.5+/-1.4 ppb) than in matched PiMM subjects (8.2+/-3.8 ppb), in healthy controls (9.3+/-2.8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DL(CO) were significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes. These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects.

2001 - Exhaled nitric oxide in patients with alpha 1 antitrypsin (AAT) deficiency. [Relazione in Atti di Convegno]
M., Malerba; Clini, Enrico; A., Radaeli; L., Corda; L., Pini; L., Ceriani; V., Grassi
abstract

nd

2001 - In-hospital short-term training program for patients with chronic airway obstruction. [Articolo su rivista]
Clini, Enrico; K., Foglio; L., Bianchi; R., Porta; M., Vitacca; N., Ambrosino
abstract

OBJECTIVE: To compare the functional benefits and relative costs of administering an intense short-term inpatient vs a longer outpatient pulmonary rehabilitation program (PRP) for patients with chronic airway obstruction (CAO). DESIGN: Retrospective case-control study. SETTING: Pulmonary ward and outpatient clinic of a rehabilitation center. PATIENTS: Forty-three patients (case subjects) selected on the basis of selection criteria were compared with control subjects matched to them for age, sex, FEV(1), and diagnosis of either COPD or asthma. Case subjects performed 10 to 12 daily sessions (5 sessions a week) of inpatient PRP; control subjects performed 20 to 24 sessions (3 sessions a week) of outpatient PRP. MEASUREMENTS: At baseline and after the PRP, an incremental exercise test was performed, including evaluation of dyspnea and leg fatigue by Borg scale (D and F, respectively) at each workload step. The cost of PRP was also evaluated. RESULTS: Both PRPs resulted in similar significant improvements in cycloergometry peak workload (from 68 +/- 18 to 82 +/- 22 and from 75 +/- 17 to 87 +/- 27 W in case subjects and control subjects, respectively), isoload D (from 6.4 +/- 1.6 to 4.2 +/- 1.8 for case subjects and from 8.5 +/- 1.9 to 6.3 +/- 2.4 for control subjects) and isoload F (from 6.6 +/- 1.8 to 4.2 +/- 1.8 for case subjects and from 8.9 +/- 1.9 to 7.0 +/- 1.8 for control subjects). Although the single daily session was less expensive, the outpatient PRP total costs were greater because of the higher number of sessions and the cost of daily transportation. CONCLUSIONS: In patients with CAO, a shorter inpatient PRP may result in improvement in exercise tolerance similar to a longer outpatient PRP but with lower costs. Whether a shorter outpatient PRP may get physiologic and clinical benefits, while further reducing costs, must be evaluated by future controlled, randomized, prospective studies.

2001 - One-year mortality in elderly stable patients with COPD. [Articolo su rivista]
P., Ranieri; R., Rozzini; S., Franzoni; M., Trabucchi; Clini, Enrico
abstract

A retrospective study was performed to evaluate the risks of one-year mortality in very old hospitalized patients including those suffering from chronic obstructive pulmonary disease (COPD). Six hundred and fifty-eight disabled patients (M = 194, mean age 79.2 +/- 7.4 years) consecutively admitted to and discharged from a Geriatric Evaluation and Rehabilitation Unit (GERU) after a comprehensive rehabilitation program were studied and divided into two groups: COPD (n = 337, 51\%) and non-COPD (n = 321, 49\%). Multidimensional evaluation including information on demographics, cognitive status [Mini Mental State Examination (MMSE)], physical health [number of diseases, Greenfield's Individual Disease Severity (IDS), and number of drugs used], functional disability [Basic Activity of Daily Living (BADL), Tinetti scale, and Physical Performance Test (PPT)], and nutritional status [Prognostic Nutritional Index (PNI)] were assessed at admission. Survival rate was assessed over a 1-year period following discharge. COPD patients mainly differed from non-COPD in terms of older age, smoking habit, number of associated diseases and drugs used. Aggregating the IDS 2-3-4 COPD classes (symptoms + functional impairment), the risk of one-year mortality was double that of the IDS 1 COPD class (symptoms only) and of non-COPD subjects (IDS 0 class) after adjusting for age, sex, disability, malnutrition, and comorbility. Moreover, IDS 2-3-4 COPD patients suffering from cor pulmonale (CP) had a fourfold 1-year risk of mortality in comparison with the IDS 1 COPD group after adjusting for the same covariates. Hospitalized stable very old COPD patients presenting functional impairment have a higher 1-year risk of mortality than only symptomatic COPD or non-COPD subjects. The presence of cor pulmonale with COPD further increases this risk.

2001 - Physiological response to pressure support ventilation delivered before and after extubation in patients not capable of totally spontaneous autonomous breathing. [Articolo su rivista]
M., Vitacca; N., Ambrosino; Clini, Enrico; R., Porta; C., Rampulla; B., Lanini; S., Nava
abstract

We designed a prospective, physiological study in 12 patients affected by chronic respiratory disorders. The study was aimed at assessing the diaphragm energy expenditure (PTPdi), lung resistance (RL) and elastance (EL), arterial blood gases (ABG), breathing pattern, and dyspnea measured by a visual analog scale during invasive pressure support ventilation (i-PSV) and noninvasive PSV (n-PSV). The ventilator settings were kept the same. Both i-PSV and n-PSV significantly reduced the PTPdi per minute, compared with that during a T-piece trial (204.4 +/- 93.8 cm H(2)O x s/min [i-PSV]; 197.5 +/- 119.8 [n-PSV]; 393.8 +/- 129.0 [T-piece]). Expired tidal volume (VTe) was significantly higher (p < 0.05) during n-PSV (615 +/- 166 ml) than during i-PSV (519 +/- 140 ml). The respiratory pump (PTPdi/VTe) was more effective (p < 0.05) with noninvasive ventilation (22.3 +/- 2.3 cm H(2)O x s/L for i-PSV versus 17.2 +/- 3.3 for n-PSV). RL and EL were similar with the two modes of ventilation. Overall dyspnea was significantly (p < 0.05) better during n-PSV than i-PSV, whereas ABG were similar. We have shown, in patients affected by stable chronic respiratory disorders not ready to sustain totally spontaneous breathing, that i-PSV and n-PSV are equally effective in reducing the PTPdi and in improving ABG, but that n-PSV seems to be better tolerated.

2000 - Endogenous nitric oxide in patients with chronic heart failure (CHF): Relation to functional impairment and nitrate-containing therapies [Articolo su rivista]
Clini, Enrico; M., Volterrani; M., Pagani; L., Bianchi; R., Porta; L. S., Gile'; A., Giordano; N., Ambrosino
abstract

We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age 55+/-9 years) were classified according to the NYHA classes I-II (n=18, group 1) and classes III-IV (n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate-). Twenty-two healthy age-related subjects served as controls (group 3). Respiratory function, symptom-limited incremental cycloergometry and resting eNO concentration at peak (FENOp) or plateau (FENOpl) of the single-breath exhalation curve were assessed in all subjects. FENOpl was significantly lower in patients than in controls (7.8+/-2.7 and 10.6+/-2.8 ppb, respectively, P<0.005) and lower in most severe CHF patients (7.1+/-2.6 and 8.8+/-2.7 ppb in group 2 and group 1, respectively, P<0.05). A significant correlation between peak V'O(2), Watts and FENOpl (r=0.42, P<0.013 and r=0.46, P=0.008, respectively) was found. Independent of NYHA class, Nitrate+ showed higher FENOp levels than Nitrate- patients (36.9+/-15.7 vs. 28. 1+/-15.1 ppb, P<0.05). Resting eNO was lower in the most compromised CHF patients and was significantly related to exercise capacity. Nitrate-containing agents might influence the levels of eNO in these patients.

2000 - Exhaled nitric oxide and exercise in stable COPD patients. [Articolo su rivista]
Clini, Enrico; L., Bianchi; M., Vitacca; R., Porta; K., Foglio; N., Ambrosino
abstract

STUDY OBJECTIVE: To evaluate exhaled nitric oxide (eNO) during exercise in patients with stable COPD. SETTING: Outpatient evaluation in a rehabilitation center. PATIENTS: Eleven consecutive male patients with stable COPD (age, 65 +/- 6 years; FEV(1), 56 +/- 10% predicted). Eight healthy (six men; age, 51 +/- 16 years) nonsmoking, nonatopic volunteers served as control subjects. METHODS: In each subject, a symptom-limited cycle ergometry test was performed by monitoring eNO with the tidal-breath method to assess eNO concentration (FENO) and output (VNO) at rest, peak exercise, and recovery time. RESULTS: Resting FENO (9.8 +/- 5.1 and 14.1 +/- 6.3 parts per billion, respectively) and VNO (4.2 +/- 2.0 and 5.9 +/- 3.4 nmol/min, respectively) were lower, although not significantly, in COPD patients than in control subjects. In both groups, FENO significantly decreased whereas VNO significantly increased during exercise. Both variables returned to baseline during the recovery time. Peak exercise VNO, but not FENO, was significantly lower in COPD patients than in control subjects (7.9 +/- 5.4 and 12.7 +/- 6.0 nmol/min, respectively, p &lt; 0.05). The rise in VNO was weakly correlated to oxygen consumption VO(2)) both in control subjects (r = 0.31, p = 0. 002) and in COPD patients (r = 0.22, p = 0.03). FENO showed an inverse correlation to VO(2) in both groups (r = -0.53, p = 0.000; r = -0.31, p = 0.003 in control subjects and COPD patients, respectively). CONCLUSIONS: In patients with mild and moderate COPD, eNO during exercise parallels that observed in normal control subjects. VNO, but not FENO, is significantly reduced at peak exercise in COPD patients as compared with control subjects. The long-term effects of exercise training on eNO has to be evaluated by further studies.

2000 - Noninvasive ventilation in COPD patients with chronic respiratory failure--pro [Articolo su rivista]
N., Ambrosino; Clini, Enrico
abstract

nd

2000 - Physiologic effects of early administered mask proportional assist ventilation in patients with chronic obstructive pulmonary disease and acute respiratory failure [Articolo su rivista]
M., Vitacca; Clini, Enrico; M., Pagani; L., Bianchi; A., Rossi; N., Ambrosino
abstract

OBJECTIVE: To evaluate the physiologic short-term effects of noninvasive proportional assist ventilation (PAV) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, physiologic study. SETTING: Respiratory intermediate intensive care unit. PATIENTS: Seven patients with acute respiratory failure requiring noninvasive mechanical ventilation because of exacerbation of COPD. INTERVENTIONS: PAV was administered by nasal mask as first ventilatory intervention. The setting of PAV involved a procedure to adjust volume assist and flow assist to levels corresponding to patient comfort. Volume assist was also set by means of the "run-away" procedure. Continuous positive airway pressure (CPAP) amounting to 2 cm H2O was always set by the ventilator. This setting of assistance (PAV) was applied for 45 mins. Thereafter, CPAP was increased to 5 cm H2O (PAV + CPAP-5) without any change in the PAV setting and was administered for 20 mins. Oxygen was delivered through a port of the mask in the attempt to maintain a target SaO2 >90\%. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases, breathing pattern, and inspiratory effort were measured during unsupported breathing and at the end of PAV, and breathing pattern and inspiratory effort were measured after 20 mins of PAV + CPAP-5. PAV determined a significant increase in tidal volume and minute ventilation (+64\% and +25\% on average, respectively) with unchanged breathing frequency and a significant improvement in arterial blood gases (PaO2 with the same oxygen supply, from 65 +/- 15 torr to 97 +/- 36 torr; PaCO2, from 80 +/- 11 torr to 76 +/- 13 torr; pH, from 7.30 +/- 0.02 to 7.32 +/- 0.03). The pressure-time product calculated over a period of 1 min (from 318 +/- 87 to 205 +/- 145 cm H2O x sec x min(-1)) was significantly reduced. PAV + CPAP-5 resulted in a further although not significant decrease in the pressure-time product calculated over a period of 1 min (to 183 +/- 110 cm H2O x sec x min(-1)), without additional changes in the breathing pattern. CONCLUSIONS: Noninvasive PAV is able to improve arterial blood gases while unloading inspiratory muscles in patients with acute exacerbation of COPD.

2000 - Preliminary results on nursing workload in a dedicated weaning center. [Articolo su rivista]
M., Vitacca; Clini, Enrico; R., Porta; N., Ambrosino
abstract

OBJECTIVE: To evaluate the nursing time required for difficult-to-wean patients in a dedicated weaning center (WC) and to examine the correlation of the nursing time with nursing workload (NW) scores and with clinical severity and dependency. SETTING: Four-bed WC of a pulmonary rehabilitation department. INTERVENTION: None. DESIGN AND MEASUREMENT: Prospective, observational study of 46 consecutive patients admitted to a long-term WC. Time required by items of the Time Oriented Score System (TOSS) and other tasks specific to respiratory intermediate intensive care units were evaluated for all the activities performed on each patient in the first 2 days after admission. Patient dependency and level of nursing care at admission were measured using the Dependence Nursing Scale (DNS) and the Intermediate Therapeutic Intervention Score System (TISS-int). The Acute Physiology and Chronic Health Evaluation (APACHE) II score was also recorded at admission. RESULTS: On the first day each patient needed 45 +/- 15\% (63 +/- 23\%, 45 +/- 22\%, and 29 +/- 14\% for the three nursing shifts) of allocated single nursing time. On the TOSS on the first day patients required a daily mean 28 +/- 10\% of total available nursing time; on the second day the results did not change. Time of care in the first 24 h was only weakly related to DNS, APACHE II score, and TISS-int; only DNS was able (although weakly; r = 0.45) to predict minutes of nursing care. CONCLUSIONS: In difficult-to-wean patients from mechanical ventilation the nursing time in the first 2 days after admission is high. The use of TOSS may underestimate NW by about 38\%. Although only DNS showed the ability to predict minutes of care, the weak relationship limits its value in clinical practice.

2000 - Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with echo-Doppler assessment [Articolo su rivista]
Clini, Enrico; G., Cremona; M., Campana; C., Scotti; M., Pagani; L., Bianchi; A., Giordano; N., Ambrosino
abstract

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.

2000 - The appropriate setting of noninvasive pressure support ventilation in stable COPD patients [Articolo su rivista]
M., Vitacca; S., Nava; M., Confalonieri; L., Bianchi; R., Porta; Clini, Enrico; N., Ambrosino
abstract

STUDY OBJECTIVE: To evaluate the short-term physiologic effects of two settings of nasal pressure-support ventilation (NPSV) in stable COPD patients with chronic hypercapnia. DESIGN: Randomized controlled physiologic study. SETTING: Lung function units and outpatient clinic of two affiliated pulmonary rehabilitation centers. PATIENTS: Twenty-three patients receiving domiciliary nocturnal NPSV for a mean (+/- SD) duration of 31 +/- 20 months. METHODS: Evaluation of arterial blood gases, breathing pattern, respiratory muscles, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) during both unassisted and assisted ventilation. Two settings of NPSV were randomly applied for 30 min each: (1) usual setting (U), the setting of NPSV actually used by the individual patient at home; and (2) physiologic setting (PHY), the level of inspiratory pressure support (IPS) and external positive end-expiratory pressure (PEEPe) tailored to patient according to invasive evaluation of respiratory muscular function and mechanics. RESULTS: All patients tolerated NPSV well throughout the procedure. Mean U was IPS, 16 +/- 3 cm H(2)O and PEEPe, 3.6 +/- 1.4 cm H(2)O; mean PHY was IPS, 15 +/- 3 cm H(2)O and PEEPe, 3.1 +/- 1.6 cm H(2)O. NPSV was able to significantly (p < 0.01) improve arterial blood gases independent of the setting applied. When compared with spontaneous breathing, both settings induced a significant increase in minute ventilation (p < 0.01). Both settings were able to reduce the diaphragmatic pressure-time product, but the reduction was significantly greater with PHY (by 64\%; p < 0.01) than with U (56\%; p < 0.05). Eleven of 23 patients (48\%) with U and 7 of 23 patients (30\%) with PHY showed ineffective efforts (IE); the prevalence of IE (20 +/- 39\% vs 6 +/- 11\% of their respiratory rate with U and PHY, respectively) was statistically different (p < 0.05). CONCLUSION: In COPD patients with chronic hypercapnia, NPSV is effective in improving arterial blood gases and in unloading inspiratory muscles independent of whether it is set on the basis of patient comfort and improvement in arterial blood gases or tailored to a patient's respiratory muscle effort and mechanics. However, setting of inspiratory assistance and PEEPe by the invasive evaluation of lung mechanics and respiratory muscle function may result in reduction in ineffective inspiratory efforts. These short-term results must be confirmed in the long-term clinical setting.

1999 - Dependence Nursing Scale: a new method to assess the effect of nursing workload in a respiratory intermediate intensive care unit. [Articolo su rivista]
Clini, Enrico; Vitacca, M; Ambrosino, N.
abstract

Non disponibile

1999 - Detection of nitric oxide in exhaled air of different animal species using a clinical chemiluminescence analyser. [Articolo su rivista]
M., Bernareggi; G., Rossoni; Clini, Enrico; E., Pasini; T., Bachetti; G., Cremona; N., Ambrosino; F., Berti
abstract

The aim of the present study was to evaluate the nitric oxide (NO) concentrations present in end-expired gas (FENO) of different animal species under basal and stimulated conditions using a clinical chemiluminescence analyser, which has been developed for measurement of single exhalations in humans. Anaesthetised, tracheotomised and artificially ventilated guinea pigs, rats and rabbits were prepared for recording systemic blood pressure and FENO. Stable levels of FENO were detected in expired air over a 1-h observation period in the three animal species tested. Rabbits exhibited the highest concentrations and output (FENO 12.9+/-1.0 ppb, VNO 9.0+/-0.7 nl min-1), followed by guinea pigs (FENO 6.2+/-0.70 ppb, VNO 1.7+/-0.19 nl min-1) and rats (FENO 0.9+/-0.01 ppb, VNO 0.25+/-0.00 nl min-1). L-arginine (1 g kg-1 i.v.) evoked significant increments in VNO in guinea pigs and rabbits but was ineffective in rats. However, L-arginine showed a direct effect on blood pressure in all the animal species tested, causing a rapid fall in the mean arterial blood pressure (MABP; 38, 48 and 50\% decrease in rabbits, guinea pigs and rats, respectively; P<0.05). An inhibitor of endogenous NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1 i.v.), decreased both basal and L-arginine-induced VNO in guinea pigs and rabbits, but was ineffective in rats. L-NAME increased MABP in all the animal species tested (58\% in guinea pigs, 43\% in rats and 18\% in rabbits; P<0.05). The results indicate that it is possible to detect NO in the exhaled air of different animal species using a clinical chemiluminescence analyser and that different species exhibit striking differences in the levels of basal and stimulated NO output.

1999 - Differences in spontaneous breathing pattern and mechanics in patients with severe COPD recovering from acute exacerbation. [Articolo su rivista]
M., Vitacca; R., Porta; L., Bianchi; Clini, Enrico; N., Ambrosino
abstract

The aims of this study were to assess spontaneous breathing patterns in patients with chronic obstructive pulmonary disease (COPD) recovering from acute exacerbation and to assess the relationship between different breathing patterns and clinical and functional parameters of respiratory impairment. Thirty-four COPD patients underwent assessment of lung function tests, arterial blood gases, haemodynamics, breathing pattern (respiratory frequency (fR), tidal volume (VT), inspiratory and expiratory time (tI and tE), duty cycle (tI/ttot), VT/tI) and mechanics (oesophageal pressure (Poes), work of breathing (WOB), pressure-time product and index, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn)). According to the presence (group 1) or absence (group 2) of Poes swings during the expiratory phase (premature inspiration), 20 (59\%) patients were included in group 1 and 14 (41\%) in group 2. Premature inspirations were observed 4.5+/-6.4 times x min(-1) (range 1-31), i.e. 20+/-21\% (3.7-100\%) of total fR calculated from VT tracings. In group 1 the coefficient of variation in VT, tE, tI/ttot, PEEPi,dyn, Poes and WOB of the eight consecutive breaths immediately preceding the premature inspiration was greater than that of eight consecutive breaths in group 2. There were no significant differences in the assessed parameters between the two groups in the overall population, whereas patients with chronic hypoxaemia in group 1 showed a more severe impairment in clinical conditions, mechanics and lung function than hypoxaemic patients in group 2. In spontaneously breathing patients with chronic obstructive pulmonary disease recovering from an acute exacerbation, detectable activity of inspiratory muscles during expiration was found in more than half of the cases. This phenomenon was not associated with any significant differences in anthropometric, demographic, physiological or clinical characteristics.

1999 - High-dose heparin impairs nitric oxide pathway and vasomotion in rats. [Articolo su rivista]
T., Bachetti; E., Pasini; Clini, Enrico; G., Cremona; R., Ferrari
abstract

BACKGROUND: Platelet-activating effects have been reported with high-dose heparin in acute thrombotic disorders. Recent studies have shown that increased platelet aggregation is due to reduced nitric oxide (NO) production in endothelial cells cultured in the presence of high-dose heparin. The aim of this study was to determine whether heparin can affect the NO pathway and the regulation of the vascular tone in vivo. METHODS AND RESULTS: Anesthetized and mechanically ventilated Sprague-Dawley rats were treated with high-dose heparin. After 4 hours, the endothelial constitutive NO synthase (ecNOS) protein content in the aorta decreased (36\% reduction, P<0.05), as detected by immunoblotting, and NO-dependent vascular reactivity was impaired. In fact, the increase in mean arterial blood pressure after inhibition of ecNOS with NG-nitro-L-arginine methyl ester (30 mg/kg) was smaller in heparin-treated animals than in controls (+26. 9+/-4.8 versus +48.3+/-9.1 mm Hg, P<0.05), and further infusion of the biological ecNOS substrate L-arginine (0.5 g/kg) was ineffective in reversing systemic vasoconstriction (-1\% versus 28\% vasodilatation, P<0.001). CONCLUSIONS: High-dose heparin can significantly affect vascular reactivity in vivo by downregulation of ecNOS protein expression.

1999 - Long-term tracheostomy in severe COPD patients weaned from mechanical ventilation. [Articolo su rivista]
Clini, Enrico; Vitacca, M; Bianchi, L; Porta, R; Ambrosino, N.
abstract

Background- It has been shown that Chronic Obstructive Pulmonary Disease (COPD) patients undergoing an episode of acute respiratory failure (ARF) requiring mechanical ventilation are at risk of relapses. Therefore it might be conceivable to maintain, at least temporarily, the tracheostomy after discharge from the ICU also in spontaneously breathing patients. The aim of this study was to evaluate the six month effects of chronic tracheostomy in severe COPD patients after weaning from mechanical ventilation.Setting- An adult four beds respiratory intermediate ICU in an Italian Respiratory Rehabilitation Department.Patients-Twenty tracheotomized COPD patients, recovering from an episode of ARF and weaned from mechanical ventilation were randomly allocated into two groups: group 1 (10 patients) maintaining their tracheal cannula, and group 2 (10 patients) having the tracheal cannula removed and their cutaneous fistula spontaneously closed. Measurements- Breathing pattern, forced lung volumes, respiratory muscle force and arterial blood gases were evaluated at discharge (T0) and at 1 (T1), 3 (T3) and 6 months (T6) after discharge; days spent in the hospital (HS), mortality rate and number of new exacerbations requiring antibiotic use were also recorded.Results- Maximal Expiratory Pressure (MEP) but not other lung function parameters significantly improved over time in both groups. Two out of 10 patients (20%) in both groups died due to respiratory causes after 5.0±0.8 months since discharge. During the follow up exacerbations (0.8 ± 0.1 vs. 0.4 ± 0.5 n/patient; p < 0.005 in group 1 and 2 respectively) but not HS were significantly greater in patients of group 1.Conclusions- Chronic tracheostomy in severe COPD patients may be associated to more frequent exacerbations requiring antibiotic treatment. When free from absolute indications of tracheostomy, COPD patients weaned from mechanical ventilation should undergo early decannulation.

1999 - Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease [Articolo su rivista]
Nava, S.; Ambrosino, N.; Clini, E.; Prato, M.; Orlando, G.; Vitacca, M.; Brigada, P.; Fracchia, C.; Rubini, R.
abstract

1999 - Physiological effects of posture on mask ventilation in awake stable chronic hypercapnic COPD patients. [Articolo su rivista]
R., Porta; M., Vitacca; Clini, Enrico; N., Ambrosino
abstract

Stable chronic hypercapnic patients are often prescribed long-term mask noninvasive pressure support ventilation (NPSV). There is a lack of information on the effects of posture on NPSV. Therefore posture induced changes in physiological effects of NPSV in awake stable chronic hypercapnic patients were evaluated. In 12 awake chronic obstructive pulmonary disease (COPD) patients breathing pattern, respiratory muscles, mechanics and dyspnoea (by visual analogue scale: VAS) were evaluated during spontaneous breathing (SB) in sitting posture and during NPSV in sitting, supine and lateral positions randomly assigned. Arterial blood gases were evaluated during SB and at the end of the last NPSV session (whatever the posture). As expected NPSV resulted in a significant improvement in carbon dioxide tension in arterial blood (Pa,CO2) (from 7.4+/-0.85 to 6.9+/-0.7 kPa). When compared with SB, sitting NPSV resulted in a significant increase in tidal volume and minute ventilation and in a significant decrease in breathing frequency. Inspiratory muscle effort as assessed by oesophageal pressure swings and pressure-time product per minute (from 14+/-4.8 to 6.2+/-3.5 cmH2O, and from 240+/-81 to 96+/-60 cmH2O x s x min(-1) respectively), intrinsic dynamic positive end expiratory pressure (from 2.7+/-2.3 to 1.4+/-1.3 cmH2O) and expiratory airway resistance (from 18+/-7 to 5+/-3 cmH2O x L x s(-1)) decreased during sitting NPSV, whereas VAS did not change. Changing posture did not significantly affect any parameter independently of the patients weight, whether obese or not. In awake stable hypercapnic chronic obstructive pulmonary disease patients changing posture does not significantly influence breathing pattern and respiratory muscles during noninvasive pressure support ventilation suggesting that mask ventilation may be performed in different positions without any relevant difference in its effectiveness.

1998 - Acute effects of deep diaphragmatic breathing in COPD patients with chronic respiratory insufficiency. [Articolo su rivista]
M., Vitacca; Clini, Enrico; L., Bianchi; N., Ambrosino
abstract

This study investigated the impact of deep diaphragmatic breathing (DB) on blood gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients recovering from an acute exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously monitored in 25 COPD patients with chronic hypercapnia, during natural breathing and DB. In eight of these patients, breathing pattern and minute ventilation (V'E) were also assessed by means of a respiratory inductance plethysmography. In five tracheostomized patients, breathing pattern and mechanics were assessed by means of a pneumotachograph/pressure transducer connected to an oesophageal balloon. Subjective rating of dyspnoea was performed by means of a visual analogue scale. In comparison to natural breathing deep DB was associated with a significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a significant increase in tidal volume and a significant reduction in respiratory rate resulting in increased V'E. During DB, dyspnoea worsened significantly and inspiratory muscle effort increased, as demonstrated by an increase in oesophageal pressure swings, pressure-time product and work of breathing. We conclude that in severe chronic obstructive pulmonary disease patients with chronic hypercapnia, deep diaphragmatic breathing is associated with improvement of blood gases at the expense of a greater inspiratory muscle loading.

1998 - Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease. [Articolo su rivista]
Clini, Enrico; L., Bianchi; M., Pagani; N., Ambrosino
abstract

BACKGROUND: Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity. METHODS: Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 < 35\% predicted with CP, n = 15; group 2, FEV1 < 35\% predicted without CP, n = 15; group 3, FEV1 > 35\% predicted, n = 23). Seventeen normal subjects served as controls. RESULTS: All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p < 0.01 ANOVA). In all subjects \% predicted FEV1 correlated slightly with PLNO but not with PNO. CONCLUSION: Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.

1998 - If and when to close tracheostomy. [Articolo su rivista]
Clini, Enrico; M., Vitacca
abstract

Non disponibile

1998 - Mechanical ventilation in chronic respiratory insufficiency: report on an Italian nationwide survey. The Italian Telethon Committee and the AIPO Study Group on Pulmonary Rehabilitation and Intensive Care. [Articolo su rivista]
M., Gasperini; Clini, Enrico; S., Zaccaria
abstract

Respiratory home care is an important aspect of rehabilitation programmes designed for patients needing long-term mechanical ventilation. Many differences have emerged between countries in the long-term care of these patients, depending on the different ways of supplying material, managing patients and providing equipment. The results of analysis of the data obtained in a preliminary survey carried out in 1995-1996 among 115 Italian centres operating in the field of home mechanical ventilation are presented. A questionnaire (all closed-circuit items) consisting of two sections (the first epidemiological, and the second methodological and economic) was sent to all centres. Fifty-seven out of 115 (50%) centres responded to the questionnaire, with a prevalence of responses from the north of Italy (37 centres). The responding centres had been working in this field for a mean period of 6 +/- 3 yrs, and a total of 1,842 patients were surveyed. The analysis focuses on the prevalence of treated diseases, methods of mechanical ventilation, regulation of prescription, evaluations carried out during follow-up, supply of equipment, costs and reimbursement, and relations with volunteer associations. A more thorough approach to all the problems emerging from this Italian survey regarding candidates for home mechanical ventilation is warranted. A more detailed comparative analysis of indications, management and costs vis-à-vis other countries should contribute towards achieving maximum uniformity of standards throughout Europe.

1998 - Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. A randomized, controlled trial. [Articolo su rivista]
S., Nava; N., Ambrosino; Clini, Enrico; M., Prato; G., Orlando; M., Vitacca; P., Brigada; C., Fracchia; F., Rubini
abstract

BACKGROUND: In patients with acute exacerbations of chronic obstructive pulmonary disease, mechanical ventilation is often needed. The rate of weaning failure is high in these patients, and prolonged mechanical ventilation increases intubation-associated complications. OBJECTIVE: To determine whether noninvasive ventilation improves the outcome of weaning from invasive mechanical ventilation. DESIGN: Multicenter, randomized trial. SETTING: Three respiratory intensive care units. PATIENTS: Intubated patients with chronic obstructive pulmonary disease and acute hypercapnic respiratory failure. INTERVENTION: A T-piece weaning trial was attempted 48 hours after intubation. If this failed, two methods of weaning were compared: 1) extubation and application of noninvasive pressure support ventilation by face mask and 2) invasive pressure support ventilation by an endotracheal tube. MEASUREMENTS: Arterial blood gases, duration of mechanical ventilation, time in the intensive care unit, occurrence of nosocomial pneumonia, and survival at 60 days. RESULTS: At admission, all patients had severe hypercapnic respiratory failure (mean pH, 7.18+/-0.06; mean PaCO2, 94.2+/-24.2 mm Hg), sensory impairment, and similar clinical characteristics. At 60 days, 22 of 25 patients (88\%) who were ventilated noninvasively were successfully weaned compared with 17 of 25 patients (68\%) who were ventilated invasively. The mean duration of mechanical ventilation was 16.6+/-11.8 days for the invasive ventilation group and 10.2+/-6.8 days for the noninvasive ventilation group (P = 0.021). Among patients who received noninvasive ventilation, the probability of survival and weaning during ventilation was higher (P = 0.002) and time in the intensive care unit was shorter (15.1+/-5.4 days compared with 24.0+/-13.7 days for patients who received invasive ventilation; P = 0.005). Survival rates at 60 days differed (92\% for patients who received noninvasive ventilation and 72\% for patients who received invasive ventilation; P = 0.009). None of the patients weaned noninvasively developed nosocomial pneumonia, whereas 7 patients weaned invasively did. CONCLUSIONS: Noninvasive pressure support ventilation during weaning reduces weaning time, shortens the time in the intensive care unit, decreases the incidence of nosocomial pneumonia, and improves 60-day survival rates.

1998 - Nursing e fisiokinesiterapia. [Capitolo/Saggio]
Clini, Enrico; N., Ambrosino
abstract

Not available

1998 - Outcome of COPD patients performing nocturnal non-invasive mechanical ventilation. [Articolo su rivista]
Clini, Enrico; C., Sturani; R., Porta; C., Scarduelli; V., Galavotti; M., Vitacca; N., Ambrosino
abstract

The role of non-invasive nocturnal domiciliary ventilation (NNV) in chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnia is still discussed. The aims of this study were to evaluate the long-term survival, the clinical effectiveness and side-effects of NNV in these patients. Forty-nine stable hypercapnic COPD patients on long-term oxygen therapy (LTOT) were assigned to two groups: in Group 1, 28 patients performed NNV by pressure support modality in addition to LTOT; in Group 2, 21 patients continued their usual LTOT regimen. Treatment was assigned according to the compliance to NNV, after an in hospital period. Mortality rate, hospital stay (HS) and ICU admissions (IA) were recorded in the two groups. HS and IA were compared to those recorded in a similar period of follow-back. Lung and respiratory muscle function, dyspnoea, and exercise capacity (by 6-min walk test) were evaluated baseline and every 3-6 months up to 3 yr. Mean follow-up time was 35 +/- 7 months. Mortality rate was not different between the two groups: 16, 33, 46\% and 13, 28, 50\% at 1, 2 and 3 yr in Groups 1 and 2 respectively. Lung and respiratory muscle function did not significantly change over time. A significant increase in 6-min walk test (from 245 +/- 78 to 250 +/- 88, 291 +/- 75, 284 +/- 89 m after 1, 2 and 3 yr respectively, P < 0.01) was observed only in patients undergoing NNV. In comparison to the follow back HS significantly decreased in both groups (from 37 +/- 29 to 15 +/- 12 and from 32 +/- 18 to 17 +/- 11 days/pt/yr in Groups 1 and 2 respectively, P < 0.001) whereas IA significantly decreased only in patients performing also NNV (from 1.0 +/- 0.7 to 0.2 +/- 0.3/pt/yr, P < 0.0001). Addition of NNV by pressure support modality to LTOT does not improve long term survival but significantly reduces ICU admissions and improves exercise capacity in severe COPD with hypercapnia.

1997 - Breathing pattern and arterial blood gases during Nd-YAG laser photoresection of endobronchial lesions under general anesthesia: use of negative pressure ventilation: a preliminary study. [Articolo su rivista]
M., Vitacca; G., Natalini; S., Cavaliere; Clini, Enrico; P., Foccoli; A., Candiani; N., Ambrosino
abstract

STUDY OBJECTIVE: To evaluate the efficacy of negative pressure ventilation (NPV) in avoiding or reducing apneas and related hypoxemia and respiratory acidosis during laser therapy (LT) of endobronchial lesions. DESIGN: A prospective, controlled, randomized study. SETTING: An operating theater of a respiratory endoscopy and laser therapy unit. POPULATION AND INTERVENTION: Twenty-seven consecutive patients referred to LT were entered into the study. Fourteen patients were randomly assigned to LT under general anesthesia and spontaneous assisted ventilation (control group) whereas in 13 cases, NPV by a poncho-wrap ventilator (NPV group) was added to the procedure. MEASUREMENTS AND RESULTS: The prevalence and the duration of apnea/hypopnea periods assessed by respiratory inductive plethysmography during LT were significantly reduced under NPV, compared to the control group. As compared to baseline, during LT, all control patients developed mild to severe hypercapnia (PaCO2 ranging from 55 to 76 mm Hg) and respiratory acidosis (pH from 7.33 to 7.19), whereas only three patients undergoing NPV (23\%) developed hypercapnia (PaCO2 from 52 to 68 mm Hg) and related acidosis (pH from 7.29 to 7.21). Optimal oxygenation was achieved in all of the patients; nevertheless, patients under NPV needed a lower mean oxygen supply; five of them (38\%) could be treated at a fraction of inspired oxygen of 0.21 for the whole procedure. CONCLUSION: NPV may be useful in reducing apneas during laser therapy under general anesthesia, thus reducing hypercapnia, related acidosis, and need of oxygen supplementation.

1997 - Breathing pattern and respiratory mechanics in chronically tracheostomized patients with chronic obstructive pulmonary disease breathing spontaneously through a hygroscopic condenser humidifier. [Articolo su rivista]
M., Vitacca; Clini, Enrico; R., Porta; N., Ambrosino
abstract

Hygroscopic condenser humidifiers (HCHs) have been proposed to artificially condition gases breathed by intubated and mechanically ventilated patients. These devices may improve viscosity and coloring of secretions, preventing further bacterial colonization, and heat inspiratory flow in chronically tracheostomized (CT) patients during spontaneous breathing. The aim of this study was to evaluate the effects of HCH on respiratory mechanics and breathing pattern in CT patients with chronic obstructive pulmonary disease (COPD) breathing spontaneously during quiet breathing and maximal voluntary ventilation (MVV). In a prospective, randomized, controlled study on 21 stable spontaneously breathing CT COPD patients, breathing pattern and respiratory mechanics were evaluated by means of a flow sensor and an esophageal pressure (Pes) catheter during quiet breathing in random order either with or without a HCH connected to the tracheostomy. Six of the patients were also studied during maximal voluntary ventilation (MVV). In comparison to without HCH, the application of HCH did not induce changes in the breathing pattern and respiratory mechanics during quiet breathing. As expected, in comparison to quiet breathing, MVV in 6 patients with HCH induced significant changes in respiratory frequency, minute ventilation, mean inspiratory flow, Pes, work of breathing, pressure time product and index. These changes were not significantly different without the application of HCH. In CT COPD patients spontaneously breathing. HCHs have no significant effects on the breathing pattern and respiratory mechanics both during quiet breathing and MVV.

1997 - Breathing pattern and respiratory mechanics in patients with amyotrophic lateral sclerosis. [Articolo su rivista]
M., Vitacca; Clini, Enrico; D., Facchetti; M., Pagani; M., Poloni; R., Porta; N., Ambrosino
abstract

The aim of this study was to evaluate the time course of breathing pattern and respiratory mechanics in patients with amyotrophic lateral sclerosis (ALS). A study was conducted on 25 out of 38 eligible ALS patients. Neurological status, arterial blood gases (ABGs), spirometry, breathing pattern (minute ventilation (V'E), tidal volume (VT), respiratory frequency (fR), duty cycle (duration of inspiration/duration of total breathing cycle (tI/ttot)), respiratory drive (P0.1)), respiratory mechanics (oesophageal pressure (Ppl), dynamic compliance (CL,dyn), pressure time product (PTP) and index (PTI), work of breathing (WOB)), and respiratory muscle (RM) strength as assessed by maximal oesophageal pressure (Ppl,max) were evaluated at presentation (to) in all patients and after 6 months (t6) in 11 patients. At to, the mean values of the degree of neurological impairment were 60+/-20 and 103+/-30 as assessed by the Norris scale and Medical Research Council (MRC) score, respectively. From the time of the first neurological symptom, survival time ranged 7-50 months. Diurnal ABGs were normal. A mild restrictive pattern was observed, a forced vital capacity (FVC) <70\% of predicted being present in 45\% of patients, only FVC \% pred (r=0.59; p<0.05), forced expiratory volume in one second (FEV1) \% pred (r=0.53; p<0.05) and survival (r=0.64; p<0.05) showing a significant correlation with the Norris scale. A Ppl,max <30 cmH2O was associated with a significantly greater mortality, Ppl,max being correlated with survival (r=0.79, p<0.05). At t6, fR, fR/VT, P0.1/Ppl,max, were significantly increased in comparison to to, while FVC \% pred, vital capacity (VC) \% pred, FEV1 \% pred, VT and Ppl,max were significantly reduced. These results suggest a progressive deterioration in breathing pattern and in respiratory muscle strength with progression of disease.

1997 - Indicazioni alla ventiloterapia notturna nell’insufficienza respiratoria. [Capitolo/Saggio]
Ambrosino, N.; Clini, E.
abstract

1997 - Non-invasive haemodynamic effects of two nasal positive pressure ventilation modalities in stable chronic obstructive lung disease patients. [Articolo su rivista]
S., Marangoni; M., Vitacca; A., Quadri; M., Schena; Clini, Enrico
abstract

The aim of this study was to compare the haemodynamic effects of a 45-min session of two modalities of non-invasive positive pressure ventilation (nPPV), by means of cardiac echo-Doppler and right heart catheterization, in chronic obstructive lung disease (COPD) patients with chronic respiratory insufficiency. Fourteen patients with stable COPD (11 males, mean age 62.9 +/- 9.8 years) underwent right heart catheterization using a floating Grandjean catheter and simultaneous echo-Doppler measurements before and during two randomly applied 45-min ventilatory sessions, consisting of nasal intermittent positive pressure ventilation in assist/control mode (nIPPV) and nasal pressure support ventilation (nPSV). Blood gases improved significantly during both modalities of ventilation. A significant increase during ventilatory sessions was found in invasive pulmonary right atrial pressure and cardiac output. A statistically significant decrease was found in the flow velocity peak of the superior vena cava and hepatic vein, and in systodiastolic flow velocity integral of the superior vena cava and hepatic vein. The inferior vena cava collapsibility index also decreased significantly during both ventilations. Right atrium diameter and area significantly decreased while right ventricular diameter significantly increased. The echo-Doppler cardiac output decreased significantly while systolic pulmonary artery pressure increased. A short session of both nIPPV and nPSV even without PEEP can induce significant haemodynamic changes in patients with stable COPD. Two-dimensional Doppler echocardiography is a non-invasive device with sufficient reliability to monitor the haemodynamic effects of nPPV. Further studies are needed to assess the effects of nPPV on vascular peripheral flows.

1997 - Patient ventilator interfaces: practical aspects in the chronic situation. [Articolo su rivista]
Clini, Enrico
abstract

In the ventilator-dependent patient, the nonpsychological problems of the chronic phase relate mainly to aspects of the patient ventilator interface. Humidification, suctioning of secretions, and ventilatory circuit and monitoring are the three most important aspects to which careful attention is needed. Good humidification can be obtained by means of various devices, which can provide humidity directly or indirectly: in the tracheostomized patient, the heat and moisture exchanger appears to be a good method because of its antibacterial properties. Airway suctioning is frequently needed in patients receiving ventilation invasively. Suctioning of secretions might possibly be associated with the risk of major cardiorespiratory complications: bacterial colonization of the airways and the subsequent increased risk of infection should be carefully considered. Problems concerning the ventilatory circuit and monitoring can be specific in patients with a tracheal cannula and those with a nasal/facial interface. Long-term tracheostomy in itself represents a real risk for bacterial colonization, damage to the tracheal mucosa, and to functioning of the vocal cords (both for speech and swallowing): therefore, a switch from invasive to noninvasive ventilatory interface may be proposed. Most problems with the nasal mask interface concern air leakage and the skin mucosal lesions. Two major aspects must be taken into account when considering the long-term effects of noninvasive ventilatory support monitoring: the possible effect of CO2 rebreathing, and the inadequate volume/pressure delivery, so that proper ventilation cannot be achieved. Use of an oral/mouth interface is of limited interest in subjects with restrictive disorders: air gastric distension and orthodontic problems are the most common side-effects in chronic use.

1996 - Acute exacerbations in patients with COPD: predictors of need for mechanical ventilation. [Articolo su rivista]
M., Vitacca; Clini, Enrico; R., Porta; K., Foglio; N., Ambrosino
abstract

Predictive factors in mechanically-ventilated patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) have been extensively studied but not in spontaneously breathing patients. The aim of this retrospective study was to evaluate the contribution of parameters of respiratory mechanics, clinical and nutritional status in predicting the need for mechanical ventilation (MV) in COPD patients treated with medical therapy for an acute exacerbation. Anthropometric data, Acute Physiology and Chronic Health Evaluation (APACHE) II score, bedside spirometry, breathing pattern, respiratory mechanics and blood gases were measured in 39 COPD patients upon hospital admission for exacerbation of their disease. Fourteen patients in whom MV was necessary were compared with 25 patients in whom medical therapy was enough for a good outcome. The discriminant analysis showed, with decreasing order of power, that nutritional prognostic index (NPI), APACHE II score, forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio, vital capacity (VC) (\% predicted) and FVC (\% pred) provided a significant distinction between the two groups. The discriminant equation considering NPI, and FVC (\% pred) could correctly predict the success in 76\% of the patients. A multiparametric stepwise regression analysis showed that APACHE II score was significantly correlated with NPI, VC (\% pred), pressure time index (PTI) and duty cycle, i.e. fraction of inspiration to duration of total breathing cycle (tl/ttot). In conclusion, underlying general conditions as assessed by malnutrition and APACHE II score were shown to be unfavourable indices of outcome for chronic obstructive pulmonary disease patients who experienced an exacerbation of their disease and were treated with medical therapy. Flow limitation data as assessed by the forced expiratory manoeuvre may provide additional information.

1996 - Airway colonization in patients with prolonged and difficult weaning from mechanical ventilation [Articolo su rivista]
Bianchi, L.; Clini, E.; Vitacca, M.; Porta, R.; Zonaro, A.; Solfrini, R.; Ambrosino, N.
abstract

Purpose: It is well known that airway colonization enhances the risk of developing ventilator associated pneumonia in Intensive Care Unite (ICU) patients. Aim of the study was to acquire more data on the incidence of colonizing pathogens in tracheostomized and/or intubated patients with difficult/prolonged weaning. Methods: From January to-December 1995 a total of 124 bacterial strains were isolated from bronchial tracheoaspirates, routinely performed in 44 consecutive, tracheostomized (32) and/or intubated (12) patients, (29 M, mean age: 66±9 years) admitted to a Respiratory Intermediate Intensive Care Unit (RIICU), to be weaned from prolonged mechanical ventilation. Mean duration of stay in RIICU was 14±2.7 days, whereas mean weaning time was 4.8±2.7 days. Pneumonia (defined as new infitrates on chest radiograph, raised white blood cell count, pirexia and the production of purulent secretions) was diagnosed in 16 patients (32%). Tracheoaspirates were performed by sterile methods. A cut-off point of 104 CFU/ml was established as an indicator of pulmonary infection. Antibiotic susceptibility was assessed using an agar disk diffusion method according to Kirby-Bauer. Results: S. aureus was the most frequently isolated pathogen among gram positive bacteria (46/48, 96%), while Ps. aeruginosa (30 isolates, 40%), Ps. putida (13 isolates, 17%) and Enterobacteriaceae (25 isolates, 32.8%) among gram negative ones (76 isolates). Concerning antibiotic susceptibility pattern, S. aureus strains were mostly (42/46, 91%) methicillin resistant, whereas among Pseudomonas spp. multiresistant strains were frequently isolated. Conclusions: Bacterial epidemiology and antibiotic susceptibility in RIICU patients may be considered similar to those staying in a classic ICU. Clinical implications: Ps.aeruginosa, Enteroactericeae and Methicillin Resistant S. aureus should always be considered as potential colonizing and infecting agents, when prescribing empiric antibiotic treatment in such critically ill patients.

1996 - Does the supine position worsen respiratory function in elderly subjects? [Articolo su rivista]
M., Vitacca; Clini, Enrico; W., Spassini; L., Scaglia; P., Negrini; A., Quadri
abstract

The aim of our study was to test whether the supine position or the sitting position worsens static, forced expiratory flows and measurements of lung mechanics in a group of aged subjects living in a nursing home who were clinically stable and without clinical evidence of cardiorespiratory diseases. Seventeen subjects (mean age 80 +/- 7 years; 16 f) were studied under baseline conditions. Spirometric, breathing pattern and mechanics data by means of an esophageal balloon were measured in sitting and supine positions. Analysis of sitting results showed aged subjects to have a slight flow limitation in peripheral airways, an increase in expiratory airways resistance and mild hyperinflation index (PEEPi = 2.2 +/- 1.9 cm H2O). Pressure time index did not reach the fatigue level in hardly any patient. Maximal inspiratory pressure values (42 +/- 15 cm H2O) were reduced by about 50\% in comparison with our normal laboratory standards. Arterial blood gas analysis revealed no pathological data in any subject. When supine, subjects revealed a significant decrease in forced expiratory volume at the first second (p < 0.005), in forced vital capacity (p < 0.01) and in peak expiratory flow (p < 0.05). Moreover, mechanics and breathing pattern data showed a significant decrease in tidal volume (Vt) and dynamic lung compliance (Cld) (p < 0.05) and an increase in respiratory rate/Vt ratio (p < 0.05). Our data confirm the results of previous reports about Cld decrease in supine posture in young normal people. Although our aged subjects showed a significant decrease in forced expiratory volumes and Vt when the supine position was adopted, static mechanics data did not appear modified by the gravitational effect of this posture.

1996 - Echo-Doppler evaluation of left ventricular impairment in chronic cor pulmonale. [Articolo su rivista]
M., Schena; Clini, Enrico; D., Errera; A., Quadri
abstract

The effects of acute right ventricular (RV) pressure and volume overloads on left ventricular (LV) filling are well known, while the significance of chronic RV pressure overload on LV function has been less studied. To evaluate the LV impairment, 30 patients with chronic cor pulmonale and pulmonary arterial hypertension secondary to chronic obstructive lung diseases (COLDs) were studied. All patients underwent respiratory tests and arterial blood gas assessment. An echo-Doppler examination was made to measure LV ejection fraction (EF), RV and LV end-diastolic and end-systolic diameters and areas, RV/LV area indexes, LV diastolic and systolic eccentricity indexes, mitral and tricuspid flow patterns, and mitral flow velocity in late and early diastole (A/E) indexes. A right heart catheterization was carried out to determine the resting mean pulmonary arterial pressure (mPAP). The data showed a marked enlargement of RV, compressing the left through a leftward shift of interventricular septum. A linear regression analysis detected a significant correlation between mPAP and the following parameters: RV/LV diastolic and systolic area indexes (r=0.75, p<0.0001; r=0.84, p<0.000, respectively), mitral A/E index (r=0.61, p<0.0005), and LV diastolic and systolic eccentricity indexes (r=0.93, p<0.0001; and r=0.83, p<0.0001). No correlations were found between echo-Doppler data and functional respiratory parameters. From these results, we conclude that chronic RV pressure overload induces LV filling impairment despite a normal systolic phase, due to septal leftward shift. In fact, chronic RV pressure overload distorts early diastolic LV geometry delaying LV filling phase, and the functional diastolic impairment of the LV is closely correlated to pulmonary hypertension levels.

1996 - Evaluation in pulmonary rehabilitation. [Articolo su rivista]
N., Ambrosino; Clini, Enrico
abstract

Non disponibile

1996 - Intermittent Negative Pressure Ventilation (INPV) during anaesthesia for Laser Therapy (LT) of endo-bronchial lesions [Articolo su rivista]
Vitacca, M.; Clini, E.; Bianchi, L.; Natalini, G.; Cavaliere, S.; Candiani, A.; Ambrosino, N.
abstract

Purpose: The aim of this study was to evaluate changes in breathing pattern and blood gases during anaesthesia with and without INPV for LT. Methods: 27 consecutive patients (mean age 60±4 years) underwent LT under general anesthesia (opioides and propofol infusion) still maintaining a residual respiratory activity at a FIO2 able to obtain a SatO2&gt; 95%. 13 out of 27 patients performed INPV by a poncho-wrap with the following setting (negative pressure 25-30 cmH2O; respiratory rate RR 10-15 acts/min). 14 matched patients (Controls) performed the procedure without INPV. Arterial blood gases were evaluated baseline and after 30 minutes since anaesthetic induction. RR, tidal volume (VT), apnoea-hyponea index (AHI) and apnoea/hyponea duration (AHD), SatO2 and heart rate (HR) were continuously recorded. Number of manual ventilation necessity (Noventil) was also recorded. Results: The table shows differences between groups under anesthesia for LT. INPV p&lt; Controls No 13 14 pH 7.35±0.08 .001 7.25±0.04 PaCO2 mmHg 47±10 .001 66±10 PaO2 mmHg 94±27 ns 126±93 O2 supply L/m 2.5±3 .005 15±4 SatO2 95±3 ns 97±3 RR act/m 13±3 ns 11±5 VTmean (% baseline) 243±125 .0005 80±28 AH Index (event/h) 16±7 .005 62±37 AH Duration (% time) 14±12 .05 50±21 HR b/m 86±14 .05 101±13 No Ventil. 0.5±0.7 .05 3±3 Conclusions: The use of INFV during anaesthesia for LT is associated to less severe levels of acidosis, to a reduction in anaesthesia induced apnoeas. Clinical implications: INVP may be proposed as an useful aid in this procedure. Further studies would demonstrate its utility in pharmacologically paralized patients.

1996 - Long-term home care programmes may reduce hospital admissions in COPD with chronic hypercapnia. [Articolo su rivista]
Clini, Enrico; M., Vitacca; K., Foglio; P., Simoni; N., Ambrosino
abstract

Long-term oxygen therapy (LTOT) has been shown to improve survival in chronic obstructive pulmonary disease (COPD) patients. The clinical effectiveness of long-term home mechanical ventilation (HMV) is still discussed, nevertheless both LTOT and HMV are often included in the home care programmes of these patients. To evaluate the effectiveness of home care programmes including either HMV or LTOT, 34 COPD patients were studied. They were admitted to either HMV (Group A: 12 males and 5 females, aged 62 +/- 5 yrs), or LTOT (Group B: 9 males and 8 females, aged 62 +/- 8 yrs). They were compared to a historical group (Group C: 19 males and 10 females, aged 67 +/- 16 yrs) performing only their usual standard LTOT during the same period. Spirometry, maximal inspiratory pressure and arterial blood gas values were assessed at baseline and at 6, 12 and 18 months of follow-up. Mortality rate and number of hospital and intensive care unit (ICU) admissions and days of hospitalization were also assessed. Four out of 17 (23\%) patients in Group A, 3 out of 17 (18\%) in Group B, and 5 out of 29 (17\%) in Group C died within 18 months. Of the lung function tests, only maximal inspiratory pressure in Group A showed a significant increase in the 18th month (50 +/- 4 to 56 +/- 7 cmH2O; p<0.01). In comparison to 18 months prior to the study, hospital admissions (from 2.2 +/- 0.6 to 1.3 +/- 1.1 and from 2.0 +/- 0.7 to 1.0 +/- 0.9 for Group A and B, respectively; p<0.005 for both), and days of hospitalization (from 60 +/- 34 to 34 +/- 40 and from 55 +/- 23 to 18 +/- 20 days in Group A and B, respectively; p<0.005 for both) significantly decreased only in the two groups submitted to the home care programme. We conclude that home care programmes may be effective in the long-term treatment of chronically hypercapnic chronic obstructive pulmonary disease patients in reducing hospital admissions.

1996 - Long-term tracheostomized COPD patients: Survival and timing for decannulation [Articolo su rivista]
Schena, M.; Clini, E.; Vitacca, M.; Porta, R.; Foglio, K.; Ambrosino, N.
abstract

Purpose: The aim of this study was to describe: 1) - the long term survival of COPD patients ventilated for more than 21 days, trachostomized and successfully weaned from mechanical ventilation (MV) and 2) - the effect of decannulation. Methods: We studied 29 COPD patients with chronic respiratory insufficiency (21 M, mean age 65±12 years, FEV1 768±290 ml, PaO2 57±14, PaCO2 49±11 mmHg at FIO2=21%) who, after successful weaning from MV were discharged from our Respiratory Intermediate Intensive Care Unit with a tracheostomy. Lung spirometry and breathing pattern, maximal inspiratory pressure (MIP), arterial blood gases, clinical condition (signs, symptoms and no of hospital/days/pts), tracheal status (skin and mucosal conditions) and microbiological status (% of colonizated patients), were recorded at discharge (T0) and every 2 months during a mean follow-up of 6±2 months (range 2 to 12 m). Results: 17 out of 29 patients (58%) (Group 1) underwent cannula removal according to subjective physician's judgment after a mean time of 4.7±2.3 months; 12 out of 29 patients (42%) (Group 2) were maintained with the tracheostomy. At T0 Pseudomonas spp. colonisation was observed in 75% of group 1 and in 66% of group 2; Staphilococcus aureus occurred only in 20% of Group 2. No difference in the functional parameters were present at this time. At the end of follow up all the patients in both groups were alive. Among all the variables considered, only MIP and respiratory frequency showed a significant improvement (p&lt;0.01) in both groups between T0 and values at the last available follow-up control. Hospital necessity in the follow up was higher in Group 2 than in Group 1 (16.1±9.8 and 8.8±7.9 days/pts respectively, p&lt;0.001). Conclusions: These data may suggest that decannulation does not influence survival in COPD patients weaned from prolonged MV, but is associated to a reduced need of new hospital admissions.

1996 - Methacholine inhaled challenge: study of correlation among different indices expressing the result. [Articolo su rivista]
Clini, Enrico; M., Vitacca; S., Scalvini; A., Quadri; K., Foglio
abstract

We tested measures of specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) versus transcutaneous oxygen tension (Ptc,O2) during inhaled methacholine bronchial challenge in 60 out-patients (38 males 22 females, mean age 33 +/- 13 yrs). The provocative doses of methacholine needed to produce a 35\% decrease of sGaw (PD35,sGaw), a 20\% fall in FEV1 (PD20,FEV1) and a 20\% decrease in Ptc,O2 (PD20,O2) were simultaneously derived from the dose-response curves. Two groups were identified according to the PD20,FEV1 result ("responders" with a PD20,FEV1 < 2,000 micrograms methacholine and "nonresponders" with PD20,FEV1 > 2,000 micrograms methacholine). All three indices derived from the dose-response curves differed significantly between the groups (p < 0.00005). The relationship analysis showed a significantly better value for PD20,O2 versus PD35,sGaw (r = 0.98) than versus PD20, FEV1 (r = 0.62). We observed similar baseline levels and variations in arterial oxygen tension (Pa,O2) and Ptc,O2 during methacholine challenge (-25 and -27\%, respectively) in 14 randomly studied responders. Thus, inhaled methacholine-induced hypoxaemia (PD20,O2) seems to reflect PD35,sGaw better than changes in FEV1. Our investigation supports the hypothesis that PD20,O2 could be useful in interpreting the methacholine inhaled challenge. It could be of help in clarifying the pathophysiological meaning of the concurrent hypoxaemia during this challenge, which should be further elucidated.

1996 - Non-invasive mechanical ventilation in severe chronic obstructive lung disease and acute respiratory failure: short- and long-term prognosis. [Articolo su rivista]
M., Vitacca; Clini, Enrico; F., Rubini; S., Nava; K., Foglio; N., Ambrosino
abstract

OBJECTIVE: To evaluate the short- and long-term prognosis of patients with chronic obstructive lung disease (COLD) who had noninvasive mechanical ventilation (NMV) for acute respiratory failure (ARF). DESIGN: Retrospective study. SETTING: Two respiratory intermediate intensive care units. PATIENTS: Two groups of patients suffering from COLD and an ARF episode requiring mechanical ventilation. Group 1 (30 patients) was given NMV using face masks (aged 64 +/- 9 years; pH = 7.28 +/- 0.05; PaCO2 = 83 +/- 18 mmHg; PaO2/FIO2 = 141 +/- 61). Group 2 (27 patients) was composed of control patients (aged = 65 +/- 8 years; pH = 7.26 +/- 0.05; PaCO2 = 75 +/- 17 mmHg; PaO2/FIO2 = 167 +/- 41) given MV using endotracheal intubation (EI) when clinical and functional conditions had further deteriorated because the medical therapy failed and NMV was not available at the time. Causes of ARF were in group 1 and 2 respectively: pneumonia in 8 (27\%) and 11 (41\%), acute exacerbation of COLD in 19 (63\%) and 14 (52\%) and pulmonary embolism in 3 (10\%) and 2 (7\%) patients. MEASUREMENTS AND RESULTS: Success rate, mortality during stay in ICU (at 3 months and at 1 year), and the need for rehospitalization during the year following ARF were measured in this study. Group 1 showed a success rate of 74\%, only 8/30 patients needing EI and conventional MV. In group 2, the weaning success was 74\% (20/27 patients). The mortality for group 1 was 20\% in IICU, 23\% at 3 months and 30\% at 1 year; and 26\% for group 2 in ICU, 48\% at 3 months and 63\% at 1 year. Within each group 1-year mortality was greater (p < 0.01) in patients with pneumonia. The number of new ICU admissions during the follow-up at 1 year was 0.12 versus 0.30 in groups 1 and 2 respectively (p < 0.05). CONCLUSION: For patients suffering from COLD who have undergone ARF, avoiding EI by early treatment with NMV is associated with better survival in comparison to patients bound to invasive MV. Pneumonia as a cause of ARF may worsen the prognosis in both groups of patients.

1996 - Pulmonary haemodynamic and respiratory mechanics in patients with chronic heart failure [Articolo su rivista]
Volterrani, M.; Vitacca, M.; Zanelli, E.; Clini, E.; Scotti, C.; Ambrosino, N.; Giordano, A.
abstract

Introduction: Abnormalities in respiratory muscle function and central haemodinamic have been described in chronic heart failure (CHF) patients (pts). Purpose: We evaluated the relationship between pulmonary haemodinamic and respiratory mechanics in these pts. Methods: Seventeen CHF pts (age 62+10; 6 in II, 8 in III, 2 in IV NYHA class) underwent right heart catheterization and simultaneous assessment of respiratory mechanics: PAPtm=pulmonary arterial trasmural pressure, Pwdtm=wedge transmural pressure, occlusion pressure=PO.1, dynamic compliance=CLdyn, pressure time product inspiratory muscles=PTP, max inspiration pressure=MIP, breathing work=WOB, pressure time index=PTI, were assessed at rest and during maximal incremental bycicle exercise test. Results: As expected pts showed, at exercise peak, a significant increase in PWdtm (30±2.5→56±2.5), PAPtm (41±3→72±2), PO.1 (1.1±0.8→3.5±2.1), PTP (164±86→470±134), CLdyn (134±73→97±55), MIP (58±17→44±20), PTI (0.07±0.05→0.2±0.1), WOB (0.7±0.3→2±.08). The relationship between haemodynamic and mechanic parameters are reported in the table. Finally, CLdyn and MIP were significantly related to VO2 peak (r=0.48, p&lt;0.05; r=0.67, p&lt;0.004 respectively). PWdtm PAPtm r p&lt; r p&lt; PO.1 0.52 0.05 0.50 0.03 PTP 0.60 0.01 0.61 0.01 CLdyn -0.42 ns -0.38 ns MIP -0.64 0.001 -0.59 0.01 PTI 0.70 0.002 0.69 0.003 WOB 0.56 0.02 0.56 0.02 Conclusions: These preliminary data show that in CHF pts baseline haemodynamic parameters are heavly influenced by respiratory mechanic. This seems to be related with functional capacity in this pts. Clinical implications: This impairment in respiratory mechanic could contribute to explain the exercise limitation in CHF pts.

1996 - [Experience of an intermediate respiratory intensive therapy in the treatment of prolonged weaning from mechanical ventilation] [Articolo su rivista]
M., Vitacca; Clini, Enrico; R., Porta; D., Sereni; N., Ambrosino
abstract

109 patients who suffered from an episode of acute respiratory failure, necessitated mechanical ventilation (MV) in a general Intensive Care Unit (ICU) and admitted to our Respiratory Intermediate Intensive Unit (RIIU), were retrospectively evaluated for outcome and weaning success. The patients, 69 +/- 9 years old, presented the following diseases: COLD (70\%), cardiovascular (15\%) and neuromuscular (15\%). A relapse of underlying disease (62\%), pneumonia (20\%), thoraco-muscular pump failure (15\%) and pulmonary embolism (3\%) were the relapsing causes needing the ICU admission. Patients remained intubated for 12 +/- 6 days and ventilated for 25 +/- 10 days. They were transferred to RIIU on pressure support ventilation (70\%); the causes of prolonged and/or difficult weaning were as following: lung failure (48\%), pump failure (12\%), cardiac and haemodynamic instability (28\%) others (12\%). Apache II score was 18 +/- 5. Maximal inspiratory pressure (31 +/- 7 cmH2O) and respiratory rate/tidal volume (83 +/- 34) were measured within 48 hours after RIIU admission. 82 subjects (75\%) were weaned after 6 +/- 4 days of MV using in 87\% of patients pressure support technique with spontaneous breathing cycles with oxygen supplementation. 8 patients on 109 (7\%) died; 20 patients on 109 (18\%) were discharged after 40 +/- 9 days of stay in RIIU necessitating home MV more than 18 hours/day by means of a tracheostomy. All patients stay in RIIU for 17 +/- 7 days with a mean cost per die of 750 thousands lire. Our data suggest that a RIIU institution for prolonged weaning in chronic diseases may be a useful solution to decrease superfluous stays in ICU decreasing costs without ba worsening in quality of care.

1995 - Non-invasive mechanical ventilation in acute respiratory failure due to chronic obstructive pulmonary disease: correlates for success. [Articolo su rivista]
N., Ambrosino; K., Foglio; F., Rubini; Clini, Enrico; S., Nava; M., Vitacca
abstract

BACKGROUND--Non-invasive mechanical ventilation is increasingly used in the treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to identify simple parameters to predict the success of this technique. METHODS--Fifty nine episodes of acute respiratory failure in 47 patients with COPD treated with non-invasive mechanical ventilation were analysed, considering each one as successful (78\%) or unsuccessful (22\%) according to survival and to the need for endotracheal intubation. RESULTS--Pneumonia was the cause of acute respiratory failure in 38\% of the unsuccessful episodes but only in 9\% of the successful ones. Success with non-invasive mechanical ventilation was associated with less severely abnormal baseline clinical and functional parameters, and with less severe levels of acidosis assessed during an initial trial of non-invasive mechanical ventilation. CONCLUSIONS--The severity of the episode of acute respiratory failure as assessed by clinical and functional compromise, and the level of acidosis and hypercapnia during an initial trial of non-invasive mechanical ventilation, have an influence on the likelihood for success with non-invasive mechanical ventilation and may prove to be useful in deciding whether to continue with this treatment.

1994 - An unusual increase in haemodynamic values in a sleep apnoea syndrome patient with prolonged apnoea. [Articolo su rivista]
M., Vitacca; Clini, Enrico; D., Facchetti; K., Foglio; S., Scalvini; A., Quadri; G. F., Levi
abstract

This case report shows the results of a right heart catheterisation in a patient with sleep apnoea syndrome (SAS). Arterial oxygen saturation (SaO2), heart rate, oronasal flow, and monitoring of electroencephalographic (EEG), sovrayoidal electromyographic (EMG) and thoracoabdominal movements were recorded simultaneously. A mixed apnoea of 180 s was registered, SaO2 fell to 54\% and systolic pulmonary artery pressure (sPAP) increased to 130 mmHg. Slowly, haemodynamic values began to normalise with the reappearance of respiratory acts. We can hypothesize that this patient's nocturnal apnoeas may cause frequent and deep negative pleural pressure swings, with severe continuous action on pulmonary circulation. This case report has shown that a SAS patient is capable of developing an adaptative response to an unusual and remarkable systolic pulmonary artery pressure increase, which is mainly due to hypoxic vasoconstriction.

1994 - Association therapy as a prognostic factor in deep fungal infection complicating oncohaematological diseases. [Articolo su rivista]
E., Pogliani; Clini, Enrico
abstract

A group of 31 oncohaemopathic patients (17 male, mean age 44 +/- 6 years), diagnosed as having primary deep fungal infection involving the lungs, were retrospectively evaluated. When infection was suspected on a clinical basis the major associated risks for death were the duration of bone marrow aplasia (12 +/- 7 versus 21 +/- 6 days, P &lt; 0.001), increase in white blood cells and, in particular, prolonged granulocytopenia (11 +/- 5 versus 24 +/- 8 days, P &lt; 0.001) when survivors were compared with patients, who died. Our therapeutic empirical approach was based on the association of i.v. amphotericin B, 1 mg kg-1 day-1, with oral 5-fluorocytosine (5-FC) 150 mg kg-1 day-1. Only 9 subjects received combination therapy for more than 7 days. For majority of them, oral 5-FC was interrupted because of altered compliance or sustained liver damage. A chi 2 test for independent parameters showed (P = 0.0021) a concentration of deaths among patients who received amphotericin B alone (15/22); none of the patients treated with amphotericin B + 5-FC (9 cases) died. Results generally suggest that a more favourable outcome was statistically associated with empirical antifungal combination therapy in deep fungal infection, although both treatment regimens showed effectiveness in terms of survival. Nevertheless the low 5-FC compliance and the small sample do not indicate the safe use of this drug in a large population.

1994 - Different modes of noninvasive intermittent positive pressure ventilation (IPPV) in acute exacerbations of COLD patients. [Articolo su rivista]
K., Foglio; Clini, Enrico; M., Vitacca
abstract

Patients with chronic obstructive lung disease may suffer from acute exacerbations of their disease, which may lead to acute respiratory failure necessitating endotracheal intubation and mechanical ventilation. We have compared retrospectively the results obtained with nasal positive pressure ventilation and those of standard medical therapy in acute relapses of severe COLD. The study showed that nasal IPPV (NIPPV) in control mode delivered for approximately 1 h, four times daily, six days a week over a 21 day period, does not result in independent improvement of acute exacerbation of COLD. In the next study the data seem to indicate, in apparent contrast, a marked reduction in the need for endotracheal intubation using noninvasive ventilation, both with assist-control and pressure support noninvasive modes, in comparison with an historical control group. We did not find a significant difference in the success rate of the two modes, but compliance to noninvasive ventilation was better with pressure support. In the former study patients showing neurological signs and requiring mechanical ventilation were excluded, while in the last study patients were selected on the basis of necessity of mechanical ventilation. The fact that in the last study, ventilation was applied by face mask instead of nasal mask may have influenced results. Further efforts are required to determine whether non-invasive ventilation is more a preventive measure to avoid endotracheal intubation, or is another means of delivering ventilatory support.

1994 - From intermediate intensive unit to home care. [Relazione in Atti di Convegno]
Clini, Enrico; M., Vitacca
abstract

The procedure of discharging the chronically ill respiratory patient from an intermediate intensive care unit (IICU) is always difficult and requires multidisciplinary intervention. A complete clinical and functional evaluation is necessary during the period of hospitalization to determine the weaning possibilities and the respiratory performance of the patient in care. In-hospital management should also be able to produce an accurate plan for home care, especially in those subjects for whom ventilatory support cannot be denied. Appropriate instruction for the care-givers involved must be provided. Funding requirements should be carefully evaluated. Four hundred and sixty five chronically, critically ill respiratory patients were admitted to our cardiopulmonary IICU (34\% of the total patients admitted) coming from intensive care units (ICUs) or other departments. The death rate was 6\%. Six patients were transferred to an ICU due to urgent necessity. Three hundred and thirty eight subjects were mechanically-ventilated (115 invasively), and 23 were finally admitted to a long-term home-care programme. Nowadays, the respiratory IICU can be considered a new hospital ward, where appropriate monitoring can be performed and accurate evaluation for discharge should be planned. Knowledge of worldwide experience is necessary to establish the best way to discharge patients from a respiratory IICU and to eventually recommend them for a home-care programme.

1994 - Hygroscopic condenser humidifiers in chronically tracheostomized patients who breathe spontaneously. [Articolo su rivista]
M., Vitacca; Clini, Enrico; K., Foglio; S., Scalvini; S., Marangoni; A., Quadri; N., Ambrosino
abstract

The aim of this study was to test the usefulness of hygroscopic condenser humidifiers on secretion and on inspired gas temperature in tracheostomized patients. Forty spontaneously breathing chronically tracheostomized patients were divided into two groups: Group 1 received a hygroscopic condenser humidifier connected to the tracheostomy, 24 h daily for 10 days; Group 2, without any protection system, was chosen as the control group. The daily number of tracheal suctions, quantity of aspirate and thickness and colouring of secretions was evaluated. At baseline, and at days 5 and 10, patients were submitted to blood gas analysis, respiratory function tests and sputum analysis. The temperature of gases breathed was measured at rest and during a hyperventilation test, with and without the hygroscopic condenser humidifier. Statistically significant differences were found in thickness and colouring of secretions between the two groups during the period of 10 days. Group 2 showed a significantly greater trend in number of bacteria than Group 1. The group with the hygroscopic condenser humidifier showed respiratory function improvement over time for forced expiratory volume in one second (FEV1) and tidal volume (VT), maximal inspiratory pressure (MIP), and maximal voluntary ventilation (MVV) in comparison to the control group, who did not. Significant differences in the temperature between rest and hyperventilation, with and without a hygroscopic condenser humidifier were also found. In conclusion, a hygroscopic condenser humidifier may be useful in chronically tracheostomized patients who breathe spontaneously, improving viscosity and colouring of secretions, preventing further bacterial colonization, heating inspiratory flow, and helping to improve the functional outcome.

1994 - Professional figures in intermediate intensive units. [Articolo su rivista]
A., Quadri; P., Simoni; Clini, Enrico; D., Errera; K., Foglio; M., Vitacca; M., Schena
abstract

In Italy, respiratory intermediate intensive care units (IICUs) are not yet considered as autonomous hospital departments. The IICU of the Rehabilitation Department of the Medical Centre of Gussago (12 monitored beds) provides care for respiratory and cardiac patients. Ventilatory assistance and noninvasive modalities both in treatment and monitoring suggest a multidisciplinary approach to the patient. Highly professional figures should, therefore, be singled out to provide care in a respiratory IICU. The medical staff is composed of one anaesthesiologist, one cardiologist and one pulmonologist, who can integrate care when respiratory complications occur in a cardiological patient, or when cardiac events affect a respiratory patient. Nurses are capable of specific activities, especially when ventilatory assistance is required. The presence of a physiotherapist reduces the nursing workload, especially for ventilated individuals. The psychological aspect is undertaken by a specialist. Finally, an expert in nutrition provides an individualized dietary regimen. Our 4 year experience encourages such a multidisciplinary approach. An ideal integration of the professional activities should provide adequate and individual care for patients admitted to an IICU.

1994 - Respiratory monitoring in an intermediate intensive unit. [Relazione in Atti di Convegno]
M., Vitacca; Clini, Enrico
abstract

The major goal of monitoring is continuous recording of indices that enhance our understanding of the underlying pathophysiology, in order to improve diagnosis and guide management, and identify trends that assist in assessing the therapeutic response and predicting prognosis. Nowadays, technology has made it possible to automatically sense and display a wide variety of physiological indices. An ideal monitoring system should be pertinent to patient management, propose interpretable data, show high technical accuracy, high sensitivity, good reproducibility, be practical to use. The international literature, our personal experience, and cost considerations have proposed the following monitoring standards as the best for a noninvasive respiratory intermediate intensive care unit (RIICU): 1) mandatory indices: respiratory rate, oxygen saturation, haemogas-analysis, tidal volume, minute ventilation, maximum voluntary ventilation, forced expiratory volume in one second, forced vital capacity, vital capacity, maximal inspiratory pressure, heart rate and blood pressure; 2) second choice indices: capnometry, respiratory inductive plethysmography, transcutaneous monitoring of gases, haemodynamic monitoring, mechanics data by means of an oesophageal balloon, and central drive. Pulmonary monitoring devices shorten the time for patients who remain on mechanical ventilators; a reduction both in the risk of associated complications and the costs involved is a natural consequence. Continuous monitoring of significant physiological indices has the potential for predicting a critical event, and providing an opportunity for the institution of lifesaving measures.

1994 - Respiratory muscle function and exercise capacity in multiple sclerosis. [Articolo su rivista]
K., Foglio; Clini, Enrico; D., Facchetti; M., Vitacca; S., Marangoni; M., Bonomelli; N., Ambrosino
abstract

Patients with multiple sclerosis (MS) show a poor exercise tolerance. A reduction in respiratory muscle strength has also been reported. The purpose of this study was to evaluate whether reduction in exercise tolerance was related to respiratory muscle dysfunction. Twenty four multiple sclerosis patients (mean +/- SD age: 48 +/- 9 yrs, duration of illness 12.2 +/- 6 yrs, severity of illness as assessed by Expanded Disability Scale Score (EDSS) 5.3 +/- 2), underwent detailed evaluation of lung function tests, arterial blood gas analysis, respiratory muscle strength and endurance, and exercise test on an arm ergometer. Sixteen of the 24 patients were able to perform the exercise test (Group I), whilst the other eight were not (group II). Arterial blood gases and lung function tests were normal for both groups. Respiratory muscle strength as assessed both by maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) was significantly reduced (MIP 18-76 cmH2O; MEP 16-82 cmH2O) compared to predicted values. Inspiratory muscle endurance time was significantly reduced in Group II in comparison to Group I (247 +/- 148 vs 397 +/- 154 s, respectively). Both MIP and MEP were significantly related to inspiratory muscle endurance time. Endurance time, MIP and MEP were inversely significantly related to duration of illness, whilst only endurance time was significantly related to Expanded Disability Scale Score.

1994 - Transcutaneous partial oxygen tension and lung mechanics during methacholine inhaled challenge. [Articolo su rivista]
Clini, Enrico; K., Foglio; M., Vitacca; A., Quadri; F., Tana
abstract

Non disponibile

1993 - Cardiopulmonary intermediate intensive unit: time course of two years activity. [Articolo su rivista]
M., Vitacca; Clini, Enrico; S., Scalvini; K., Foglio; A., Quadri; G., Levi
abstract

Intermediate intensive care may be defined as a post comprehensive programme, where monitoring, combined with necessary treatment, improves and maintains physiological functions to complete the cure of underlying diseases. The aims of this paper are: 1) to describe the caring activity that patients admitted to our 12 bed Cardiopulmonary Intermediate Intensive Unit (CPIIU) experience and, 2) to demonstrate that a noninvasive choice does not worsen mortality and the quality of care needed to improve patient outcome. From September 1st 1990 to September 30th 1992, 775 patients (135 respiratory subjects) were admitted. The majority of these patients came from Coronary Intensive Units or Medical and Surgical Intensive Care Units. Noninvasive cardiorespiratory monitoring was assessed in these patients, to obtain their clinical improvement. After this post acute observance, our patients were followed during a stabilization programme in the cardiopulmonary rehabilitation division until a day-hospital or home care programme was carried out. By implementing the CPIIU principles in our department we have reduced the number of deaths and the necessity for Intensive Care Unit admission (from 19 to 9.6\%). The estimated risk of death proposed by Apache score was higher than that recorded in our patients (estimated Apache = 25 and 6\% for respiratory and cardiac patients, respectively; actual Apache = 10.4 and 3.1\% for the same patients, respectively). Average hospitalisation days in our CPIIU was 18 +/- 9. Our CPIIU showed a mean daily cost for each patient of $370.6.

1993 - Non invasive assessment of physiopathologic events during methacholine inhaled test in asthmatics [Articolo su rivista]
Clini, E.; Marangoni, S.; Vitacca, M.; Scalvini, S.; Foglio, K.; Quadri, A.
abstract

Respiratory and pulmonary vascular modifications induced by methacholine inhaled challenge in 20 asthmatic outpatients were studied non invasively by means of echo-Doppler. Eight healthy volunteers were studied as a control group. A significant reduction in oxemia (-22 mmHg) as a hyperreactive marker (PD15O2) was observed in asthmatics and it was strictly related to PD20FEV1(r = 0.82 and p &lt; 0.005). Again in asthmatics we observed a significant increase in sPAP (from 27±2 to 39±9 mmHg) evaluated by means of echo-Doppler: This variation was time related to hypoxic phase. Hypoxemia lasted 9±5 minutes but neither this index nor the basal lung function or the methacholine challenge results were related to the echo-Doppler measurements which were useful for evaluating the pulmonary vascular response. Finally our study suggests that: a) a significant decrease in oxemia was strictly related to the bronchial response in asthmatics; b) a transient increase in sPAP was present and time related to hypoxia only asthmatics; C) the lack of relationship among vascular and bronchial response was probably due to different distribution of ventilatory and vascular reflexes in each subject.

1992 - Ceftizoxime in Lower Respiratory Tract Infection: A Multicentre Clinical Study [Articolo su rivista]
Clini, V.; Clini, E.; Tana, F.; Messa, A.; Garotta, F.; Pamparana, F.
abstract

1991 - Air quality and respiratory health in citizens of great Milan [Articolo su rivista]
Clini, E; Damato, S.
abstract

1991 - Metacholine inhaled challenge and bronchial responsiveness [Articolo su rivista]
Clini, E; Colombo, C; Damato, S; Meregalli, G; Tana, F; Allegra, L.
abstract

Two groups of 53 subjects (24 healthy volunteers and 29 affected from allergy or suffering with chronic cough or wheezing) were submitted to inhaled metacholine challenge. An appropriate software provided the calculation of FEV1 and sGaw values at single metacholine doses and described 8 parameters through the linear and parabolic regressions (PD20 FEV1 log and par, PD35sGaw log and par, Slope FEV1 and sGaw, Area FEV1 and sGaw). Multiple correlation among parameters and anova analysis revealed a good correlation between linear and parabolic regression values for FEV1 and sGaw and suggested PD35sGaw log as the best parameter to detect responders and non-responders.

1991 - The role of the MEF in the early evaluation of respiratory function in air pollution induced obstructive lung diseases [Articolo su rivista]
Damato, S; Clini, E; Spagnotto, S.
abstract

1990 - Fungal infection and haematological malignancies: a report about association therapy with amphotericin B and 5-flucytosine in primary lung involvement. [Articolo su rivista]
E., Pogliani; CLINI, Enrico
abstract

Non disponibile

1990 - Treatment of acute infections of the respiratory tract. The cytiolone-ampicillin relationship: A study of therapeutic effectiveness and tolerability [Articolo su rivista]
Clini, V.; Clini, E.
abstract

A random double-blind study is reported, investigating whether the addition of a mucolytic and muco-regulating drug such as cytiolone is advantageous over the antibiotic ampicillin alone in the treatment of a febrile infection of the respiratory system (acute bronchitis, acute tracheobronchitis and bronchial pneumonia with mucous hypersecretion). An expectoration volume greater than 20 ml per day was a criterion for participation in the study. Patients were randomly divided into two groups of 20 each. Each group received either (i) Mucorex-Ampicillin (0.3 g of cytiolone, 1.2 g of benzidine ampicillin and 0.3 g of sodium ampicillin) by i.m. injection once daily in the morning; or (ii) 1.2 g of benzidine ampicillin by one i.m. injection in the morning. The duration of treatment was seven days. The results indicate that the addition of cytiolone reduces the severity of the clinical pattern, with rapid improvement and a reduction of the principle symptoms. © 1990.

1989 - Airway obstructions due to distilled water aerosol [Articolo su rivista]
Tana, F; Fiaccabrino, V; Meregalli, G; Noseda, E; Clini, E.
abstract

1989 - [Pulmonary mycosis as a complication of acute leukemia in the adult. Diagnostic study] [Articolo su rivista]
Clini, Enrico; P., Maffé; E., Pogliani; E. E., Polli
abstract

Pulmonary fungal infections complicating hematological malignancies are difficult to diagnose antemortem because clinical findings are actually considered to be not specific. From December 1984 to June 1986 we documented the clinical findings in sixteen patients, 9 with ANLL, 6 with ALL and 1 with CML + BC; all patients were diagnosed as pulmonary fungal infection and treated for this complication. Pulmonary infiltrates occurred after severe aplasia (range 5-90 days) or during bone marrow relapse. We studied pulmonary signs and symptoms (pleuritic pain, cough, hemoptysis, shortness of breath, rales, rub, bronchial murmur) both at the beginning and during the management of this infectious complication and we related them to chest x-ray findings, the duration of granulocytopenia, and fever. Our purpose was to identify clinical characteristics for these episodes and establish roentgenological criteria for prognosis. These findings should improve the possibilities for an early diagnosis and prompt treatment.

1988 - Bitolterol mesylate inhalant in COPD in vivo bronchodilator activity [Articolo su rivista]
Clini, E; Numeroso, R; Pelizza, A; De Rosa, G; Clini, V.
abstract

1984 - Determination of the energy load of erythrocytes in long-distance and medium-distance runners [Articolo su rivista]
Accorsi, A.; Fazi, A.; Bechi, G.; Clini, E.; Stocchi, V.
abstract

In this study erythrocytes drawn from well-trained athletes (middle- and long-distance runners) and from sedentary subjects have been compared for their adenine nucleotide contents. ADP and AMP appeared to be significantly (p less than 0,001) increased only in red cells from athletes in the rest state. After athletes' race this difference with control subjects become insignificant. Nevertheless, the observed ADP and AMP modifications are not great enough to influence the energy charge (CE) of the compared erythrocytes.