Bianca BEGHE' - personale UniMoRe

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Bianca BEGHE'

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

Pubblicazioni

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.

2022 - ERS statement: A core outcome set for clinical trials evaluating the management of COPD exacerbations [Articolo su rivista]
Mathioudakis, A. G.; Abroug, F.; Agusti, A.; Ananth, S.; Bakke, P.; Bartziokas, K.; Beghe, Bianca.; Bikov, A.; Bradbury, T.; Brusselle, G.; Cadus, C.; Coleman, C.; Contoli, M.; Corlateanu, A.; Corlateanu, O.; Criner, G. J.; Csoma, B.; Emelyanov, A.; Faner, R.; Romero, G. F.; Hammouda, Z.; Horvath, P.; Garcia, A. H.; Jacobs, M.; Jenkins, C.; Joos, G.; Kharevich, O.; Kostikas, K.; Lapteva, E.; Lazar, Z.; Leuppi, J. D.; Liddle, C.; Linnell, J.; Lopez-Giraldo, A.; Mcdonald, V. M.; Nielsen, R.; Papi, A.; Saraiva, I.; Sergeeva, G.; Sioutkou, A.; Sivapalan, P.; Stovold, E.; Wang, H.; Wen, F.; Yorke, J.; Williamson, P. R.; Vestbo, J.; Jensen, J. -U.
abstract

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

2022 - Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE) [Articolo su rivista]
Contoli, M.; Santus, P.; Menzella, F.; Rocchi, C.; Radovanovic, D.; Baraldi, F.; Martelli, C.; Casanova, S.; Barbetta, C.; Micheletto, C.; Scichilone, N.; Beghe, Bianca; Carpagnano, E.; Papi, A.
abstract

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments.

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 - Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study [Articolo su rivista]
Braido, F.; Blasi, F.; Canonica, G. W.; Paggiaro, P.; Beghe', B.; Bonini, M.; Carpagnano, G. E.; Del Giacco, S.; Lavorini, F.; Milanese, M.; Patella, V.; Santus, P.; Contoli, M.
abstract

Objective: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80–90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences. Methods: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844). Results and conclusion: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease. Abbreviations: MANI: Mild/Moderate Asthma Network of Italy SANI: Severe Asthma Network Italy GINA: Global Initiative for Asthma SABA: short acting β2-agonists ICS: inhaled corticosteroids CRF: Case Report Form.

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; Beghè, 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 - Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation [Articolo su rivista]
Mikus, M. S.; Kolmert, J.; Andersson, L. I.; Ostling, J.; Knowles, R. G.; Gomez, C.; Ericsson, M.; Thorngren, J. -O.; Khoonsari, P. E.; Dahlen, B.; Kupczyk, M.; de Meulder, B.; Auffray, C.; Bakke, P. S.; Beghe, Bianca; Bel, E. H.; Caruso, M.; Chanez, P.; Chawes, B.; Fowler, S. J.; Gaga, M.; Geiser, T.; Gjomarkaj, M.; Horvath, I.; Howarth, P. H.; Johnston, S. L.; Joos, G.; Krug, N.; Montuschi, P.; Musial, J.; Nizankowska-Mogilnicka, E.; Olsson, H. K.; Papi, A.; Rabe, K. F.; Sandstrom, T.; Shaw, D. E.; Siafakas, N. M.; Uhlen, M.; Riley, J. H.; Bates, S.; Middelveld, R. J. M.; Wheelock, C. E.; Chung, K. F.; Adcock, I. M.; Sterk, P. J.; Djukanovic, R.; Nilsson, P.; Dahlen, S. -E.; James, A.; Ahmed, H.; Balgoma, D.; Bansal, A. T.; Baribaud, F.; Bigler, J.; Billing, B.; Bisgaard, H.; Boedigheimer, M. J.; Bonnelykke, K.; Brandsma, J.; Brinkman, P.; Bucchioni, E.; Burg, D.; Bush, A.; Chaiboonchoe, A.; Checa, T.; Compton, C. H.; Corfield, J.; Cunoosamy, D.; D'Amico, A.; Emma, R.; Erpenbeck, V. J.; Erzen, D.; Fichtner, K.; Fitch, N.; Fleming, L. J.; Formaggio, E.; Frey, U.; Gahlemann, M.; Goss, V.; Guo, Y. -K.; Hashimoto, S.; Haughney, J.; Hedlin, G.; Hekking, P. -P. W.; Higenbottam, T.; Hohlfeld, J. M.; Holweg, C. T. J.; Knox, A. J.; Konradsen, J.; Lazarinis, N.; Lefaudeux, D.; Li, T.; Loza, M. J.; Lutter, R.; Manta, A.; Masefield, S.; Matthews, J. G.; Mazein, A.; Meiser, A.; Miralpeix, M.; Mores, N.; Murray, C. S.; Myles, D.; Naz, S.; Nordlund, B.; Pahus, L.; Pandis, I.; Pavlidis, S.; Postle, A.; Powel, P.; Rao, N.; Reinke, S.; Roberts, A.; Roberts, G.; Rowe, A.; Schofield, J. P. R.; Seibold, W.; Selby, A.; Sigmund, R.; Singer, F.; Sjodin, M.; Skipp, P. J.; Sousa, A. R.; Sun, K.; Thornton, B.; Uddin, M.; van Aalderen, W. M.; van Geest, M.; Vestbo, J.; Vissing, N. H.; Wagener, A. H.; Wagers, S. S.; Weiszhart, Z.; Wheelock, C. E.; Wheelock, A.; Wilson, S. J.; Yasinska, V.; Brusselle, G. G.; Campbell, D. A.; Contoli, M.; Damm, K.; de Rudder, I.; Delin, I.; Devautour, C.; Duplaga, M.; Eduards, M.; Ek, A.; Ekstrom, T.; Figiel, E.; Gaber, F.; Gauw, S.; Gawlewicz-Mroczka, A.; Gerding, D.; Haque, S.; Hewitt, L.; Hiemstra, P. S.; Holgate, S. T.; Holloway, J.; Kania, A.; Kanniess, F.; Karlsson, O.; Kips, J. C.; Kumlin, M.; Lantz, A. -S.; Lazarinis, N.; Magnussen, H.; Mallia, P.; Martling, I.; Meziane, L.; Oikonomidou, E.; Olsson, M.; Pace, E.; Papadopouli, E.; Papadopoulos, N.; Plataki, M.; Profita, M.; Reinius, L. E.; Richter, K.; Robinson, D. S.; Romagnoli, M.; Samara, K.; Schelfhout, V.; Skedinger, M.; Stamataki, E.; ten Brinke, A.; Vachier, I.; Wallen-Nielsen, E.; van Veen, I.; Weersink, E.; Wilson, S. J.; Yasinska, V.; Zervas, E.; Ziolkowska-Graca, B.
abstract

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

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 - 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 - Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19 [Articolo su rivista]
Bousquet, J.; Anto, J. M.; Czarlewski, W.; Haahtela, T.; Fonseca, S. C.; Iaccarino, G.; Blain, H.; Vidal, A.; Sheikh, A.; Akdis, C. A.; Zuberbier, T.; Hamzah Abdul Latiff, A.; Abdullah, B.; Aberer, W.; Abusada, N.; Adcock, I.; Afani, A.; Agache, I.; Aggelidis, X.; Agustin, J.; Akdis, M.; Al-Ahmad, M.; Al-Zahab Bassam, A.; Alburdan, H.; Aldrey-Palacios, O.; Alvarez Cuesta, E.; Alwan Salman, H.; Alzaabi, A.; Amade, S.; Ambrocio, G.; Angles, R.; Annesi-Maesano, I.; Ansotegui, I. J.; Ara Bardajo, P.; Arasi, S.; Arshad, H.; Cristina Artesani, M.; Asayag, E.; Avolio, F.; Azhari, K.; Bachert, C.; Bagnasco, D.; Baiardini, I.; Bajrovic, N.; Bakakos, P.; Bakeyala Mongono, S.; Balotro-Torres, C.; Barba, S.; Barbara, C.; Barbosa, E.; Barreto, B.; Bartra, J.; Bateman, E. D.; Battur, L.; Bedbrook, A.; Bedolla Barajas, M.; Beghe', B.; Bekere, A.; Bel, E.; Ben Kheder, A.; Benson, M.; Berghea, E. C.; Bergmann, K. -C.; Bernardini, R.; Bernstein, D.; Bewick, M.; Bialek, S.; Bialoszewski, A.; Bieber, T.; Billo, N. E.; Bilo, M. B.; Bindslev-Jensen, C.; Bjermer, L.; Bobolea, I.; Bochenska Marciniak, M.; Bond, C.; Boner, A.; Bonini, M.; Bonini, S.; Bosnic-Anticevich, S.; Bosse, I.; Botskariova, S.; Bouchard, J.; Boulet, L. -P.; Bourret, R.; Bousquet, P.; Braido, F.; Briggs, A.; Brightling, C. E.; Brozek, J.; Brussino, L.; Buhl, R.; Bumbacea, R.; Buquicchio, R.; Burguete Cabanas, M. -T.; Bush, A.; Busse, W. W.; Buters, J.; Caballero-Fonseca, F.; Calderon, M. A.; Calvo, M.; Camargos, P.; Camuzat, T.; Canevari, F. R.; Cano, A.; Canonica, G. W.; Capriles-Hulett, A.; Caraballo, L.; Cardona, V.; Carlsen, K. -H.; Carmon Pirez, J.; Caro, J.; Carr, W.; Carreiro-Martins, P.; Carreon-Asuncion, F.; Carriazo, A. -M.; Casale, T.; Castor, M. -A.; Castro, E.; Caviglia, A. G.; Cecchi, L.; Cepeda Sarabia, A.; Chandrasekharan, R.; Chang, Y. -S.; Chato-Andeza, V.; Chatzi, L.; Chatzidaki, C.; Chavannes, N. H.; Chaves Loureiro, C.; Chelninska, M.; Chen, Y.; Cheng, L.; Chinthrajah, S.; Chivato, T.; Chkhartishvili, E.; Christoff, G.; Chrystyn, H.; Chu, D. K.; Chua, A.; Chuchalin, A.; Chung, K. F.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Cirule, I.; Coelho, A. C.; Compalati, E.; Constantinidis, J.; Correia de Sousa, J.; Costa, E. M.; Costa, D.; Costa Dominguez, M. D. C.; Coste, A.; Cottini, M.; Cox, L.; Crisci, C.; Crivellaro, M. A.; Cruz, A. A.; Cullen, J.; Custovic, A.; Cvetkovski, B.; Czarlewski, W.; D'Amato, G.; da Silva, J.; Dahl, R.; Dahlen, S. -E.; Daniilidis, V.; Darjazininahhas, L.; Darsow, U.; Davies, J.; de Blay, F.; De Feo, G.; De Guia, E.; de los Santos, C.; De Manuel Keenoy, E.; De Vries, G.; Deleanu, D.; Demoly, P.; Denburg, J.; Devillier, P.; Didier, A.; Dimic Janjic, S.; Dimou, M.; Dinh-Xuan, A. T.; Djukanovic, R.; Do Ceu Texeira, M.; Dokic, D.; Dominguez Silva, M. G.; Douagui, H.; Douladiris, N.; Doulaptsi, M.; Dray, G.; Dubakiene, R.; Dupas, E.; Durham, S.; Duse, M.; Dykewicz, M.; Ebo, D.; Edelbaher, N.; Eiwegger, T.; Eklund, P.; El-Gamal, Y.; El-Sayed, Z. A.; El-Sayed, S. S.; El-Seify, M.; Emuzyte, R.; Enecilla, L.; Erhola, M.; Espinoza, H.; Espinoza Contreras, J. G.; Farrell, J.; Fernandez, L.; Fink Wagner, A.; Fiocchi, A.; Fokkens, W. J.; Lenia, F.; Fonseca, J. A.; Fontaine, J. -F.; Forastiere, F.; Fuentes Perez, J. M.; Gaerlan-Resureccion, E.; Gaga, M.; Galvez Romero, J. L.; Gamkrelidze, A.; Garcia, A.; Garcia Cobas, C. Y.; Garcia Cruz, M. D. L. L. H.; Gayraud, J.; Gelardi, M.; Gemicioglu, B.; Gennimata, D.; Genova, S.; Gereda, J.; Gerth van Wijk, R.; Giuliano, A.; Gomez, M.; Gonzalez Diaz, S.; Gotua, M.; Grigoreas, C.; Grisle, I.; Gualteiro, L.; Guidacci, M.; Guldemond, N.; Gutter, Z.; Guzman, A.; Halloum, R.; Halpin, D.; Hamelmann, E.; Hammadi, S.; Harvey, R.; Heffler, E.; Heinrich, J.; Hejjaoui, A.; Hellquist-Dahl, B.; Hernandez Velazquez, L.; Hew, M.; Hossny, E.; Howarth, P.; Hrubisko, M.; Huerta Villalobos, Y. R.; Humbert, M.; Salina, H.; Hyland, M.; Ibrahim, M.; Ilina, N.; Illario, M.; Incorvaia, C.; Infantino, A.; Irani, C.; Ispayeva, Z.; Ivancev
abstract

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.

2021 - Chronic obstructive pulmonary disease exacerbation fundamentals: Diagnosis, treatment, prevention and disease impact [Articolo su rivista]
MacLeod, M.; Papi, A.; Contoli, M.; Beghe', B.; Celli, B. R.; Wedzicha, J. A.; Fabbri, L. M.
abstract

In chronic obstructive pulmonary disease (COPD), exacerbations (ECOPD), characterized by an acute deterioration in respiratory symptoms, are fundamental events impacting negatively upon disease progression, comorbidities, wellbeing and mortality. ECOPD also represent the largest component of the socioeconomic burden of COPD. ECOPDs are currently defined as acute worsening of respiratory symptoms that require additional therapy. Definitions that require worsening of dyspnoea and sputum volume/purulence assume that acute infections, especially respiratory viral infections, and/or exposure to pollutants are the main cause of ECOPD. But other factors may contribute to ECOPD, such as the exacerbation of other respiratory diseases and non-respiratory diseases (e.g., heart failure, thromboembolism). The complexity of worsening dyspnoea has suggested a need to improve the definition of ECOPD using objective measurements such as blood counts and C-reactive protein to improve accuracy of diagnosis and a personalized approach to management. There are three time points when we can intervene to improve outcomes: acutely, to attenuate the length and severity of an established exacerbation; in the aftermath, to prevent early recurrence and readmission, which are common, and in the long-term, establishing preventative measures that reduce the risk of future events. Acute management includes interventions such as corticosteroids or antibiotics and measures to support the respiratory system, including non-invasive ventilation (NIV). Current therapies are broad and better understanding of clinical phenotypes and biomarkers may help to establish a more tailored approach, for example in relation to antibiotic prescription. Other unmet needs include effective treatment for viruses, which commonly cause exacerbations. Preventing early recurrence and readmission to hospital is important and the benefits of interventions such as antibiotics or anti-inflammatories in this period are not established. Domiciliary NIV in those patients who are persistently hypercapnic following discharge and pulmonary rehabilitation can have a positive impact. For long-term prevention, inhaled therapy is key. Dual bronchodilators reduce exacerbation frequency but in patients with continuing exacerbations, triple therapy should be considered, especially if blood eosinophils are elevated. Other options include phosphodiesterase inhibitors and macrolide antibiotics. ECOPD are a key component of the assessment of COPD severity and future outcomes (quality of life, hospitalisations, health care resource utilization, mortality) and are a central component in pharmacological management decisions. Targeted therapies directed towards specific pathways of inflammation are being explored in exacerbation prevention, and this is a promising avenue for future research.

2021 - Copd, pulmonary fibrosis and ilas in aging smokers: The paradox of striking different responses to the major risk factors [Articolo su rivista]
Beghe', B.; Cerri, S.; Fabbri, L. M.; Marchioni, A.
abstract

Aging and smoking are associated with the progressive development of three main pulmonary diseases: chronic obstructive pulmonary disease (COPD), interstitial lung abnormalities (ILAs), and idiopathic pulmonary fibrosis (IPF). All three manifest mainly after the age of 60 years, but with different natural histories and prevalence: COPD prevalence increases with age to >40%, ILA prevalence is 8%, and IPF, a rare disease, is 0.0005–0.002%. While COPD and ILAs may be associated with gradual progression and mortality, the natural history of IPF remains obscure, with a worse prognosis and life expectancy of 2–5 years from diagnosis. Acute exacerbations are significant events in both COPD and IPF, with a much worse prognosis in IPF. This perspective discusses the paradox of the striking pathological and pathophysiologic responses on the background of the same main risk factors, aging and smoking, suggesting two distinct pathophysiologic processes for COPD and ILAs on one side and IPF on the other side. Pathologically, COPD is characterized by small airways fibrosis and remodeling, with the destruction of the lung parenchyma. By contrast, IPF almost exclusively affects the lung parenchyma and interstitium. ILAs are a heterogenous group of diseases, a minority of which present with the alveolar and interstitial abnormalities of interstitial lung disease.

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 - Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation [Articolo su rivista]
Delgado-Eckert, E.; James, A.; Meier-Girard, D.; Kupczyk, M.; Andersson, L. I.; Bossios, A.; Mikus, M.; Ono, J.; Izuhara, K.; Middelveld, R.; Dahlen, B.; Gaga, M.; Siafakas, N. M.; Papi, A.; Beghe', B.; Joos, G.; Rabe, K. F.; Sterk, P. J.; Bel, E. H.; Johnston, S. L.; Chanez, P.; Gjomarkaj, M.; Howarth, P. H.; Nizankowska-Mogilnicka, E.; Dahlen, S. -E.; Frey, U.
abstract

Background: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. Objective: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. Methods: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. Results: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). Conclusion: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.

2021 - Rate of Decline of FEV1 as a Biomarker of Survival? [Articolo su rivista]
Papi, A.; Beghe', B.; Fabbri, L. M.
abstract

2021 - Real-world experience with dupilumab in severe asthma: One-year data from an italian named patient program [Articolo su rivista]
Campisi, R.; Crimi, C.; Nolasco, S.; Beghe', B.; Antonicelli, L.; Guarnieri, G.; Scichilone, N.; Porto, M.; Macchia, L.; Scioscia, G.; Barbaro, M. P. F.; Papi, A.; Crimi, N.
abstract

Introduction: Dupilumab is a monoclonal antibody targeting IL-4Rα recently licensed for severe asthma (SA). A Named Patients Program (NPP) was created in Italy before its commercial availability for SA patients with no other available therapeutic options. We aimed to assess the real-world effectiveness of dupilumab in patients with SA and unmet needs. Methods: We performed a multicentre retrospective study, including SA patients admitted to the NPP treated with dupilumab for 12 months. Data on the number of exacerbations, Asthma Control Test (ACT), pre-bronchodilator FEV1%, oral corticosteroids (OCSs) use, FeNO and eosinophils count in peripheral blood were recorded at baseline and after 3, 6, and 12 months. Results: We included 18 SA patients (mean age 53.3±12.4 years, 66.7% female). Eleven (61.1%) were OCSs dependent. Five patients (27.8%) received previous anti-IgE and/or antiIL-5 agents. A significant improvement in ACT score (from 15.7±5.1 to 18.8±4.8, p=0.023), OCSs intake [10 (5–25) mg/day to 0 (0–5) mg/day, p=0.0333] and FeNO [from 25 (20–80) ppb to 21 (10.9–55.3) ppb, p=0.0190] was already detected after 3 months of treatment. After 12 months, a statistically significant decrease in the number of exacerbations from 2 (0–3) to 0 (0–1) (p<0.0068) and increase in FEV1% from 73.5±19.5% to 87.1±19.2% (p=0.0407) and ACT to a mean value of 22.4±1.7 (p<0.0001) and the interruption of OCSs in all the patients (p<0.0001) was observed. A transient increase in the eosinophil count was observed in five patients (above 1000 cells/μL in 2 cases) after 3 months, without any clinical effect. Conclusion: Dupilumab improved all the explored clinical outcomes after 12 months, and the transient hypereosinophilia did not modify treatment response. These real-world data confirm the results reported in randomized controlled trials and provide an important opportunity to characterize the clinical impact of the treatment in a non-trial setting. Further real-world studies with a larger cohort of patients are needed to confirm these findings.

2020 - Chronic cough in adults [Abstract in Rivista]
Spanevello, A.; Beghe', B.; Visca, D.; Fabbri, L. M.; Papi, A.
abstract

Cough, a defense mechanism for clearing the airways of secretions, exudate, or foreign bodies, may become a troublesome symptom. Chronic cough, one of the most frequent symptoms requiring medical attention, is often not due to identifiable causes in adults. Chronic productive cough defines chronic bronchitis, and thus is present in 100% of these patients, and frequently in patients with bronchiectasis, cystic fibrosis, and chronic infectious respiratory diseases. However, chronic cough is most frequently dry. Thus, chronic cough in adults is a difficult syndrome requiring multidisciplinary approaches, particularly to diagnose and treat the most frequent identifiable causes, but also to decide which patients may benefit by treating the central cough hypersensitivity by neuromodulatory therapy and/or non-pharmacologic treatment (speech pathology therapy). Recent guidelines provide algorithms for diagnosis and assessment of cough severity; particularly chronic cough in adults. After excluding life-threatening diseases, chronic cough due to identifiable causes (triggers and/or diseases), particularly smoking and/or the most frequent diseases (asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic bronchitis, and adverse reactions to drugs [angiotensin-converting enzyme inhibitors and sitagliptin]) should be treated by avoiding triggers and/or according to guidelines for each underlying disease. In patients with troublesome chronic cough due to unknown causes or persisting even after adequate avoidance of triggers, and/or treatment of the underlying disease(s), a symptomatic approach with neuromodulators and/or speech pathology therapy should be considered. Additional novel promising neuromodulatory agents in clinical development (e.g., P2X3 inhibitors) will hopefully become available in the near future.

2020 - Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air® App [Articolo su rivista]
Bedard, A.; Anto, J. M.; Fonseca, J. A.; Arnavielhe, S.; Bachert, C.; Bedbrook, A.; Bindslev-Jensen, C.; Bosnic-Anticevich, S.; Cardona, V.; Cruz, A. A.; Fokkens, W. J.; Garcia-Aymerich, J.; Hellings, P. W.; Ivancevich, J. C.; Klimek, L.; Kuna, P.; Kvedariene, V.; Larenas-Linnemann, D.; Melen, E.; Monti, R.; Mosges, R.; Mullol, J.; Papadopoulos, N. G.; Pham-Thi, N.; Samolinski, B.; Tomazic, P. V.; Toppila-Salmi, S.; Ventura, M. T.; Yorgancioglu, A.; Bousquet, J.; Pfaar, O.; Basagana, X.; Aberer, W.; Agache, I.; Akdis, C. A.; Akdis, M.; Aliberti, M. R.; Almeida, R.; Amat, F.; Angles, R.; Annesi-Maesano, I.; Ansotegui, I. J.; Arnavielle, S.; Asayag, E.; Asarnoj, A.; Arshad, H.; Avolio, F.; Bacci, E.; Baiardini, I.; Barbara, C.; Barbagallo, M.; Baroni, I.; Barreto, B. A.; Bateman, E. D.; Bedolla-Barajas, M.; Bewick, M.; Beghe', B.; Bel, E. H.; Bergmann, K. C.; Bennoor, K. S.; Benson, M.; Bertorello, L.; Bialoszewski, A. Z.; Bieber, T.; Bialek, S.; Bjermer, L.; Blain, H.; Blasi, F.; Blua, A.; Bochenska Marciniak, M.; Bogus-Buczynska, I.; Boner, A. L.; Bonini, M.; Bonini, S.; Bosse, I.; Bouchard, J.; Boulet, L. P.; Bourret, R.; Bousquet, P. J.; Braido, F.; Briedis, V.; Brightling, C. E.; Brozek, J.; Bucca, C.; Buhl, R.; Buonaiuto, R.; Panaitescu, C.; Burguete Cabanas, M. T.; Burte, E.; Bush, A.; Caballero-Fonseca, F.; Caillaud, D.; Caimmi, D.; Calderon, M. A.; Camargos, P. A. M.; Camuzat, T.; Canfora, G.; Canonica, G. W.; Carlsen, K. H.; Carreiro-Martins, P.; Carriazo, A. M.; Carr, W.; Cartier, C.; Casale, T.; Castellano, G.; Cecchi, L.; Cepeda, A. M.; Chavannes, N. H.; Chen, Y.; Chiron, R.; Chivato, T.; Chkhartishvili, E.; Chuchalin, A. G.; Chung, K. F.; Ciaravolo, M. M.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Carvalho Coehlo, A. C.; Colas, L.; Colgan, E.; Coll, J.; Conforti, D.; Constantinidis, J.; Correia de Sousa, J.; Cortes-Grimaldo, R. M.; Corti, F.; Costa, E.; Costa-Dominguez, M. C.; Courbis, A. L.; Cox, L.; Crescenzo, M.; Custovic, A.; Czarlewski, W.; Dahlen, S. E.; D'Amato, G.; Dario, C.; da Silva, J.; Dauvilliers, Y.; Darsow, U.; De Blay, F.; De Carlo, G.; Dedeu, T.; de Fatima Emerson, M.; De Feo, G.; De Vries, G.; De Martino, B.; Motta Rubini, N. P.; Deleanu, D.; Denburg, J. A.; Devillier, P.; Di Capua Ercolano, S.; Di Carluccio, N.; Didier, A.; Dokic, D.; Dominguez-Silva, M. G.; Douagui, H.; Dray, G.; Dubakiene, R.; Durham, S. R.; Du Toit, G.; Dykewicz, M. S.; El-Gamal, Y.; Eklund, P.; Eller, E.; Emuzyte, R.; Farrell, J.; Farsi, A.; Ferreira de Mello, J.; Ferrero, J.; Fink-Wagner, A.; Fiocchi, A.; Fontaine, J. F.; Forti, S.; Fuentes-Perez, J. M.; Galvez-Romero, J. L.; Gamkrelidze, A.; Garcia-Cobas, C. Y.; Garcia-Cruz, M. H.; Gemicioglu, B.; Genova, S.; Christoff, G.; Gereda, J. E.; Gerth van Wijk, R.; Gomez, R. M.; Gomez-Vera, J.; Gonzalez Diaz, S.; Gotua, M.; Grisle, I.; Guidacci, M.; Guldemond, N. A.; Gutter, Z.; Guzman, M. A.; Haahtela, T.; Hajjam, J.; Hernandez, L.; Hourihane, J. O. '. B.; Huerta-Villalobos, Y. R.; Humbert, M.; Iaccarino, G.; Illario, M.; Ispayeva, Z.; Jares, E. J.; Jassem, E.; Johnston, S. L.; Joos, G.; Jung, K. S.; Just, J.; Jutel, M.; Kaidashev, I.; Kalayci, O.; Kalyoncu, A. F.; Karjalainen, J.; Kardas, P.; Keil, T.; Keith, P. K.; Khaitov, M.; Khaltaev, N.; Kleine-Tebbe, J.; Kowalski, M. L.; Kuitunen, M.; Kull, I.; Kupczyk, M.; Krzych-Falta, E.; Lacwik, P.; Laune, D.; Lauri, D.; Lavrut, J.; Le, L. T. T.; Lessa, M.; Levato, G.; Li, J.; Lieberman, P.; Lipiec, A.; Lipworth, B.; Lodrup Carlsen, K. C.; Louis, R.; Lourenco, O.; Luna-Pech, J. A.; Magnan, A.; Mahboub, B.; Maier, D.; Mair, A.; Majer, I.; Malva, J.; Mandajieva, E.; Manning, P.; De Manuel Keenoy, E.; Marshall, G. D.; Masjedi, M. R.; Maspero, J. F.; Mathieu-Dupas, E.; Matta Campos, J. J.; Matos, A. L.; Maurer, M.; Mavale-Manuel, S.; Mayora, O.; Meco, C.; Medina-Avalos, M. A.; Melo-Gomes, E.; Meltzer, E. O.; Menditto, E.; Mercier, J.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Moda, G.; Mogica-Martinez, M. D.; Mohammad, Y.; Momas, I.; Montef
abstract

Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.

2020 - Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement [Articolo su rivista]
Bousquet, J.; Akdis, C. A.; Jutel, M.; Bachert, C.; Klimek, L.; Agache, I.; Ansotegui, I. J.; Bedbrook, A.; Bosnic-Anticevich, S.; Canonica, G. W.; Chivato, T.; Cruz, A. A.; Czarlewski, W.; Del Giacco, S.; Du, H.; Fonseca, J. A.; Gao, Y.; Haahtela, T.; Hoffmann-Sommergruber, K.; Ivancevich, J. -C.; Khaltaev, N.; Knol, E. F.; Kuna, P.; Larenas-Linnemann, D.; Mullol, J.; Naclerio, R.; Ohta, K.; Okamoto, Y.; O'Mahony, L.; Onorato, G. L.; Papadopoulos, N. G.; Pfaar, O.; Samolinski, B.; Schwarze, J.; Toppila-Salmi, S.; Ventura, M. -T.; Valiulis, A.; Yorgancioglu, A.; Zuberbier, T.; Pawankar, R.; Mubeccel, A.; Mona, A. -A.; Emilio, A. C.; Hasan, A.; Cristina, A. M.; Zeinab, A.; Mostafa, B. E.; Sergio, B.; Cristina, B.; Eric, B.; Bianca, B.; Elisabeth, B.; Larl-Christian, B.; David, B.; Leif, B.; Attilio, B.; Sergio, B.; Isabelle, B.; Jacques, B.; Louis-Philippe, B.; Fulvio, B.; Christopher, B.; Roland, B.; Carmen, B.; Andrew, B.; William, B.; Fernan, C. -F.; Davide, C.; Silvia, C.; Paulo, C.; Walter, C.; Vicky, C.; Kai-Hakon, C.; Warner, C.; Thomas, C.; Lorenzo, C.; Alfonso, C. M.; Niels, C.; Ekaterine, C.; George, C.; Derek, C.; Cemal, C.; Giorgio, C.; Ieva, C.; Sousa Jaime, C. D.; Maria del Carmen, C. D.; Andre, C.; Linda, C.; Alvaro, C.; Adnan, C.; Ulf, D.; Frederic, D. B.; Diana, D.; Pascal, D.; Philippe, D.; Alain, D.; Ratko, D.; Maria, D. C. T.; Dejan, D.; Ruta, D.; Stephen, D.; Patrik, E.; Yehia, E. -G.; Regina, E.; Bieren Julia, E. -V.; Alessandro, F.; Wytske, F.; Mina, G.; Luis, G. R. J.; Bilun, G.; Sonya, G.; Jose, G.; Maximiliano, G.; Maia, G.; Ineta, G.; Marta, G.; Antonieta, G. M.; Adnan, H.; Elham, H.; Jonathan, H.; Martin, H.; Yunuen, H. V.; Guido, I.; Carla, I.; Zhanat, I.; Edgardo, J.; Ewa, J.; Erika, J. -J.; Sebastian, J.; Guy, J.; Ki-Suck, J.; Jocelyne, J.; Igor, K.; Omer, K.; Fuat, K.; Przemyslaw, K.; Jussi, K.; Jorg, K. -T.; Gerard, K.; Marek, K.; Mikael, K.; Violeta, K.; Amir, L.; Susanne, L.; Lan, L.; Marcus, L.; Michael, L.; Jing, L.; Philip, L.; Brian, L.; Karin, L. C.; Bassam, M.; Mika, M.; Hans-Jorgen, M.; Gailen, M.; Pedro, M.; Mohammad, M.; Juan-Jose, M.; Cem, M.; Erik, M.; Eli, M.; Hans, M.; Jean-Pierre, M.; Florin, M.; Neven, M.; Branislava, M.; Yousser, M.; Mathieu, M.; Mario, M. -A.; Ralph, M.; Lars, M.; Antonella, M.; Tihomir, M.; Alla, N.; Leyla, N. -B.; Kristof, N.; Laurent, N.; Robyn, O.; Kimihiro, O.; Brian, O.; Luigi, P. P.; Isabella, P. -S.; Petr, P.; Nilos, P.; Sim, P. H.; Ruby, P.; Ana, P.; Bernard, P.; Constantinos, P.; Davor, P.; Wolfgang, P.; Todor, P.; Fabienne, P.; Paul, P.; Lars, P.; Emmanuel, P.; Claus, R.; Stella, R. M.; Janet, R.; Jose Angelo, R.; Graham, R.; Nicolas, R.; Antonino, R.; Jose, R. -P.; Nelson, R.; Lanny, R.; Philip, R.; Dermot, R.; Mario, S. -B.; Joaquin, S. -D.; Glenis, S.; Elie, S.; Nikolaos, S.; Estelle, S.; Juan-Carlos, S.; Dirceu, S.; Talant, S.; Manuel, S. -M.; Cristiana, S.; Rafael, S.; Timo, S.; Charlotte, S. U.; Carel, T.; Peter-Valentin, T.; Massimo, T.; Ioana, T.; Marilyn, U. P.; Erkka, V.; Eric, V. G.; Marianne, V. H.; Olivier, V.; Petra, V.; Martin, W.; Dana, W.; Yun, W. D.; Susan, W.; Magnus, W.; Dennis, W.; Barbara, Y.; Arzu, Y.; Osman, Y.; Mario, Z.; Mihaela, Z.; Beghe', Bianca
abstract

2020 - Management of chronic refractory cough in adults [Articolo su rivista]
Visca, D.; Beghe', B.; Fabbri, L. M.; Papi, A.; Spanevello, A.
abstract

Cough is a common respiratory symptom that is considered to be chronic when it lasts more than eight weeks. When severe, chronic cough may significantly impact an individual's quality of life, and such patients are frequently referred for specialist evaluation. Current international guidelines provide algorithms for the management of chronic cough: in most cases, treatment of the underlying disease is sufficient to improve or resolve cough symptoms. Severe chronic cough may significantly affect patients' quality of life and necessitate frequent referral for specialist evaluations. In this narrative review, we summarize non-pharmacologic and pharmacologic management of adult patients with chronic cough of known cause that persists after proper treatment (chronic refractory cough, CRC) or chronic cough of unknown cause in adult patients. If chronic cough persists even after treatment of the underlying disease, or if the chronic cough is not attributable to any cause, then a symptomatic approach with neuromodulators may be considered, with gabapentin as the first choice, and opioids or macrolides as alternatives. Speech pathology treatment and/or neuromodulators should be discussed with patients and alternative options carefully considered, taking into account risk/benefit. Novel promising drugs are under investigation (e.g. P2×3 inhibitors), but additional studies are needed in this field. Speech pathology can be combined with a neuromodulator to give an enhanced treatment response of longer duration suggesting that non-pharmacologic treatment may play a key role in the management of CRC.

2020 - Multimorbidity in COPD, does sleep matter? [Articolo su rivista]
Vanfleteren, L. E.; Beghe', B.; Andersson, A.; Hansson, D.; Fabbri, L. M.; Grote, L.
abstract

A good night's sleep is a prerequisite for sustainable mental and physical health. Sleep disorders, including sleep disordered breathing, insomnia and sleep related motor dysfunction (e.g., restless legs syndrome), are common in patients with chronic obstructive pulmonary disease (COPD), especially in more severe disease. COPD is commonly associated with multimorbidity, and sleep disorders as a component of this multimorbidity spectrum have a further negative impact on COPD-related comorbidities. Indeed, concomitant diseases in COPD and in obstructive sleep apnea (OSA) are similar, suggesting that the combination of COPD and OSA, the so called OSA-COPD overlap syndrome (OVS), affects patient outcomes. Potential clinically important interactions of OVS exist in cardiovascular and metabolic disease, arthritis, anxiety, depression, neurocognitive disorder and the fatigue syndrome. Correct diagnosis for recognition and treatment of sleep-related disorders in COPD is recommended. However, surprisingly limited information is available and further research and improved diagnostic tools are needed. In the absence of clear evidence, we agree with the recommendation of the Global Initiative on Chronic Obstructive Lung Disease that sleep disorders should be actively searched for and treated in patients with COPD. We believe that both aspects are important components of the holistic approach required in patients with chronic multimorbid conditions.

2020 - Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies [Articolo su rivista]
Bousquet, J.; Cristol, J. -P.; Czarlewski, W.; Anto, J. M.; Martineau, A.; Haahtela, T.; Fonseca, S. C.; Iaccarino, G.; Blain, H.; Fiocchi, A.; Canonica, G. W.; Fonseca, J. A.; Vidal, A.; Choi, H. -J.; Kim, H. J.; Le Moing, V.; Reynes, J.; Sheikh, A.; Akdis, C. A.; Zuberbier, T.; Abdul Latiff, A. H.; Abdullah, B.; Aberer, W.; Abusada, N.; Adcock, I.; Afani, A.; Agache, I.; Aggelidis, X.; Agustin, J.; Akdis, C. A.; Akdis, M.; Al-Ahmad, M.; Al-Zahab Bassam, A.; Alburdan, H.; Aldrey-Palacios, O.; Alvarez Cuesta, E.; Alwan Salman, H.; Alzaabi, A.; Amade, S.; Ambrocio, G.; Angles, R.; Annesi-Maesano, I.; Ansotegui, I. J.; Anto, J. M.; Ara Bardajo, P.; Arasi, S.; Arrais, M.; Arshad, H.; Artesani, M. -C.; Asayag, E.; Avolio, F.; Azhari, K.; Bachert, C.; Bagnasco, D.; Baiardini, I.; Bajrovic, N.; Bakakos, P.; Bakeyala Mongono, S.; Balotro-Torres, C.; Barba, S.; Barbara, C.; Barbosa, E.; Barreto, B.; Bartra, J.; Basagana, X.; Bateman, E. D.; Battur, L.; Bedbrook, A.; Bedolla Barajas, M.; Beghe', B.; Bekere, A.; Bel, E.; Ben Kheder, A.; Benson, M.; Berghea, E. -C.; Bergmann, K. -C.; Bernardini, R.; Bernstein, D.; Bewick, M.; Bialek, S.; Bialoszewski, A.; Bieber, T.; Billo, N. E.; Bilo, M. -B.; Bindslev-Jensen, C.; Bjermer, L.; Blain, H.; Bobolea, I.; Bochenska Marciniak, M.; Bond, C.; Boner, A.; Bonini, M.; Bonini, S.; Bosnic-Anticevich, S.; Bosse, I.; Botskariova, S.; Bouchard, J.; Boulet, L. -P.; Bourret, R.; Bousquet, P.; Braido, F.; Briggs, A.; Brightling, C. E.; Brozek, J.; Brussino, L.; Buhl, R.; Bumbacea, R.; Buquicchio, R.; Burguete Cabanas, M. -T.; Bush, A.; Busse, W. W.; Buters, J.; Caballero-Fonseca, F.; Calderon, M. A.; Calvo, M.; Camargos, P.; Camuzat, T.; Canevari, F.; Cano, A.; Canonica, G. W.; Capriles-Hulett, A.; Caraballo, L.; Cardona, V.; Carlsen, K. -H.; Carmona Pirez, J.; Caro, J.; Carr, W.; Carreiro-Martins, P.; Carreon-Asuncion, F.; Carriazo, A. -M.; Carrionyribas, C.; Casale, T.; Castor, M. -A.; Castro, E.; Caviglia, A. G.; Cecchi, L.; Cepeda Sarabia, A.; Chalubinski, M.; Chandrasekharan, R.; Chang, Y. -S.; Chato-Andeza, V.; Chatzi, L.; Chatzidaki, C.; Chavannes, N. H.; Chaves Loureiro, C.; Chavez Garcia, A. -A.; Chelninska, M.; Chen, Y.; Cheng, L.; Chinthrajah, S.; Chivato, T.; Chkhartishvili, E.; Christoff, G.; Chrystyn, H.; Chu, D. K.; Chua, A.; Chuchalin, A.; Chung, K. F.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Cirule, I.; Coelho, A. -C.; Compalati, E.; Constantinidis, J.; Correia de Sousa, J.; Costa, E. M.; Costa, D.; del Carmen Costa Dominguez, M.; Coste, A.; Cottini, M.; Cox, L.; Crisci, C.; Crivellaro, M. A.; Cruz, A. A.; Cullen, J.; Custovic, A.; Cvetkovski, B.; Czarlewski, W.; D'Amato, G.; da Silva, J.; Dahl, R.; Dahlen, S. -E.; Daniilidis, V.; Darjazini Nahhas, L.; Darsow, U.; Davies, J.; de Blay, F.; De Feo, G.; De Guia, E.; De la Torre Navarrete, J. -R.; De los Santos, C.; De Manuel Keenoy, E.; De Vries, G.; Deleanu, D.; Demoly, P.; Denburg, J.; Devillier, P.; Didier, A.; Dimic Janjic, S.; Dimou, M.; Dinh-Xuan, A. T.; Djukanovic, R.; Do Ceu Texeira, M.; Dokic, D.; Dominguez Silva, M. G.; Douagui, H.; Douladiris, N.; Doulaptsi, M.; Dray, G.; Dubakiene, R.; Dupas, E.; Durham, S.; Duse, M.; Dykewicz, M.; Ebo, D.; Edelbaher, N.; Eiwegger, T.; Eklund, P.; El-Gamal, Y.; El-Sayed, Z. A.; El-Sayed, S. S.; El-Seify, M.; Emuzyte, R.; Enecilla, L.; Erhola, M.; Espinoza, H.; Espinoza Contreras, J. G.; Farrell, J.; Fernandez, L.; Fimbres Jimenez, P.; Fink Wagner, A.; Fiocchi, A.; Fokkens, W. J.; Folletti, L.; Fonseca, J. A.; Fontaine, J. -F.; Forastiere, F.; Fuentes Perez, J. M.; Gaerlan-Resureccion, E.; Gaga, M.; Galvez Romero, J. L.; Gamkrelidze, A.; Garcia, A.; Garcia Cobas, C. Y.; de la Luz Hortensia Garcia Cruz, M.; Ortiz, V. G.; Gayraud, J.; Gelardi, M.; Gemicioglu, B.; Gennimata, D.; Genova, S.; Gereda, J.; Gerth van Wijk, R.; Giuliano, A.; Gomez, R. -M.; Gonzalez Ballester, M. -A.; Gonzalez Diaz, S.; Gotua, M.; Grigoreas, C.; Grisle, I.; Guidacci, M.; Guldemond, N.; Gutter, Z.; Guzman, A.; Haahtela, T.; Ha
abstract

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

2019 - Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology [Articolo su rivista]
Bousquet, J.; Hellings, P. W.; Agache, I.; Amat, F.; Annesi-Maesano, I.; Ansotegui, I. J.; Anto, J. M.; Bachert, C.; Bateman, E. D.; Bedbrook, A.; Bennoor, K.; Bewick, M.; Bindslev-Jensen, C.; Bosnic-Anticevich, S.; Bosse, I.; Brozek, J.; Brussino, L.; Canonica, G. W.; Cardona, V.; Casale, T.; Cepeda Sarabia, A. M.; Chavannes, N. H.; Cecchi, L.; Correia de Sousa, J.; Costa, E.; Cruz, A. A.; Czarlewski, W.; De Carlo, G.; De Feo, G.; Demoly, P.; Devillier, P.; Dykewicz, M. S.; El-Gamal, Y.; Eller, E. E.; Fonseca, J. A.; Fontaine, J. -F.; Fokkens, W. J.; Guzman, M. -A.; Haahtela, T.; Illario, M.; Ivancevich, J. -C.; Just, J.; Kaidashev, I.; Khaitov, M.; Kalayci, O.; Keil, T.; Klimek, L.; Kowalski, M. L.; Kuna, P.; Kvedariene, V.; Larenas-Linnemann, D.; Laune, D.; L. T. T., Le; Carlsen, K. L.; Lourenco, O.; Mahboub, B.; Mair, A.; Menditto, E.; Milenkovic, B.; Morais-Almeida, M.; Mosges, R.; Mullol, J.; Murray, R.; Naclerio, R.; Namazova-Baranova, L.; Novellino, E.; O'Hehir, R. E.; Ohta, K.; Okamoto, Y.; Okubo, K.; Onorato, G. L.; Palkonen, S.; Panzner, P.; Papadopoulos, N. G.; Park, H. -S.; Paulino, E.; Pawankar, R.; Pfaar, O.; Plavec, D.; Popov, T. A.; Potter, P.; Prokopakis, E. P.; Rottem, M.; Ryan, D.; Salimaki, J.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Sisul, J. -C.; Rajabian-Soderlund, R.; Sooronbaev, T.; Stellato, C.; To, T.; Todo-Bom, A. -M.; Tomazic, P. -V.; Toppila-Salmi, S.; Valero, A.; Valiulis, A.; Valovirta, E.; Ventura, M. -T.; Wagenmann, M.; Wang, D. Y.; Wallace, D.; Waserman, S.; Wickman, M.; Yorgancioglu, A.; Zhang, L.; Zhong, N.; Zidarn, M.; Zuberbier, T.; Aberer, W.; Akdis, C. A.; Akdis, M.; Alberti, M. R.; Almeida, R.; Angles, R.; Arnavielle, S.; Asayag, E.; Asarnoj, A.; Arshad, H.; Avolio, F.; Bacci, E.; Baiardini, I.; Barbara, C.; Barbagallo, M.; Baroni, I.; Barreto, B. A.; Basagana, X.; Bedolla-Barajas, M.; Beghé, Bianca.; Bel, E. H.; Bergmann, K. C.; Benson, M.; Bertorello, L.; Bialoszewski, A. Z.; Bieber, T.; Bialek, S.; Bjermer, L.; Blain, H.; Blasi, F.; Blua, A.; Bochenska Marciniak, M.; Bogus-Buczynska, I.; Boner, A. L.; Bonini, M.; Bonini, S.; Bouchard, J.; Boulet, L. P.; Bourret, R.; Braido, F.; Briedis, V.; Brightling, C. E.; Bucca, C.; Buhl, R.; Buonaiuto, R.; Panaitescu, C.; Burguete Cabanas, M. T.; Burte, E.; Bush, A.; Caballero-Fonseca, F.; Caillot, D.; Caimmi, D.; Calderon, M. A.; Camargos, P. A. M.; Camuzat, T.; Canfora, G.; Carreiro-Martins, P.; Carriazo, A. M.; Carr, W.; Cartier, C.; Castellano, G.; Chen, Y.; Chiron, R.; Chivato, T.; Chkhartishvili, E.; Chuchalin, A. G.; Chung, K. F.; Ciaravolo, M. M.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Carvalho Coehlo, A. C.; Colas, L.; Colgan, E.; Coll, J.; Conforti, D.; Cortes-Grimaldo, R. M.; Corti, F.; Costa-Dominguez, M. C.; Courbis, A. L.; Cox, L.; Crescenzo, M.; Custovic, A.; Dahlen, S. E.; Dario, C.; da Silva, J.; Dauvilliers, Y.; Darsow, U.; De Blay, F.; Dedeu, T.; de Fatima Emerson, M.; De Vries, G.; De Martino, B.; de Paula Motta Rubini, N.; Deleanu, D.; Denburg, J. A.; Di Capua Ercolano, S.; Di Carluccio, N.; Didier, A.; Dokic, D.; Dominguez-Silva, M. G.; Douagui, H.; Dray, G.; Dubakiene, R.; Durham, S. R.; Du Toit, G.; Eklund, P.; Emuzyte, R.; Farrell, J.; Farsi, A.; Ferreira de Mello, J.; Ferrero, J.; Fink-Wagner, A.; Fiocchi, A.; Forti, S.; Fuentes-Perez, J. M.; Galvez-Romero, J. L.; Gamkrelidze, A.; Garcia-Aymerich, J.; Garcia-Cobas, C. Y.; Garcia-Cruz, M. H.; Gemicioglu, B.; Genova, S.; George, C.; Gereda, J. E.; Gerth van Wijk, R.; Gomez, R. M.; Gomez-Vera, J.; Gonzalez Diaz, S.; Gotua, M.; Grisle, I.; Guidacci, M.; Guldemond, N. A.; Gutter, Z.; Hajjam, J.; Hernandez, L.; Hourihane, J. O.; Huerta-Villalobos, Y. R.; Humbert, M.; Iaccarino, G.; Jares, E. J.; Jassem, E.; Johnston, S. L.; Joos, G.; Jung, K. S.; Jutel, M.; Kalyoncu, A. F.; Karjalainen, J.; Kardas, P.; Keith, P. K.; Khaltaev, N.; Kleine-Tebbe, J.; Kuitunen, M.; Kull, I.; Kupczyk, M.; Krzych-Falta, E
abstract

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.

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 - Circadian rhythm of COPD symptoms in clinically based phenotypes. Results from the STORICO Italian observational study [Articolo su rivista]
Scichilone, N.; Antonelli Incalzi, R.; Blasi, F.; Schino, P.; Cuttitta, G.; Zullo, A.; Ori, A.; Canonica, G.; Schino, P.; Cuttitta, G.; Foschino, M. P.; Prediletto, R.; Tranfa, C. M. E.; Zappa, M. C.; Patriciello, P.; Labate, L.; Mariotta, S.; Nava, S.; Vatrella, A.; Mastroberardino, M.; Sarzani, R.; Iuliano, A.; Maggi, L.; Zedda, A.; Pesci, A.; Sera, G.; Nicolini, A.; Salvatore Walter, D. D.; Forte, S.; Mario, D. D.; Rivolta, F.; Ferliga, M.; Raco, A. F.; Luigi, D. R.; Cabibbo, G.; Maselli, R.; Gulotta, C.; Nardini, S.; Guffanti, E. E.; Castellani, W.; Triolo, L.; Passalacqua, G.; Beghe', B.; Salvatore, L. C.; Faccini, E.; Atzeni, E.; Tazza, R.; Giamesio, P.
abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) encompasses various phenotypes that severely limit the applicability of precision respiratory medicine. The present investigation is aimed to assess the circadian rhythm of symptoms in pre-defined clinical COPD phenotypes and its association with health-related quality of life (HR-QoL), the quality of sleep and the level of depression/anxiety in each clinical phenotype. Methods: The STORICO (NCT03105999) Italian observational prospective cohort study enrolled COPD subjects. A clinical diagnosis of either chronic bronchitis (CB), emphysema (EM) or mixed COPD-asthma (MCA) phenotype was made by clinicians at enrollment. Baseline early-morning, day-time and nocturnal symptoms (gathered via the Night-time, Morning and Day-time Symptoms of COPD questionnaire), HR-QoL (via the St. George's Respiratory Questionnaire), anxiety and depression levels (via the Hospital Anxiety and Depression Scale), quality of sleep (via COPD and Asthma Sleep Impact Scale), physical activity (via the International Physical Activity Questionnaire) as well as lung function were recorded. Results: 606 COPD subjects (age 71.4 ± 8.2 years, male 75.1%) were studied. 57.9, 35.5 5.3 and 1.3% of the sample belonged to the CB, EM, MCA and EM + CB phenotypes respectively. The vast majority of subjects reported early-morning and day-time symptoms (79.5 and 79.2% in the CB and 75.8 and 77.7% in the EM groups); the proportion suffering from night-time symptoms was higher in the CB than in the EM group (53.6% vs. 39.5%, p = 0.0016). In both CB and EM, indiscriminately, the presence of symptoms during the 24-h day was associated with poorer HR-QoL, worse quality of sleep and higher levels of anxiety/depression. Conclusions: The findings highlight the primary classificatory role of nocturnal symptoms in COPD. Trial registration: Trial registration number: NCT03105999, date of registration: 10th April 2017.

2019 - Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma [Articolo su rivista]
Bousquet, J.; Bedbrook, A.; Czarlewski, W.; Onorato, G. L.; Arnavielhe, S.; Laune, D.; Mathieu-Dupas, E.; Fonseca, J.; Costa, E.; Lourenco, O.; Morais-Almeida, M.; Todo-Bom, A.; Illario, M.; Menditto, E.; Canonica, G. W.; Cecchi, L.; Monti, R.; Napoli, L.; Ventura, M. T.; De Feo, G.; Fokkens, W. J.; Chavannes, N. H.; Reitsma, S.; Cruz, A. A.; Da Silva, J.; Serpa, F. S.; Larenas-Linnemann, D.; Fuentes Perez, J. M.; Huerta-Villalobos, Y. R.; Rivero-Yeverino, D.; Rodriguez-Zagal, E.; Valiulis, A.; Dubakiene, R.; Emuzyte, R.; Kvedariene, V.; Annesi-Maesano, I.; Blain, H.; Bonniaud, P.; Bosse, I.; Dauvilliers, Y.; Devillier, P.; Fontaine, J. F.; Pepin, J. L.; Pham-Thi, N.; Portejoie, F.; Picard, R.; Roche, N.; Rolland, C.; Schmidt-Grendelmeier, P.; Kuna, P.; Samolinski, B.; Anto, J. M.; Cardona, V.; Mullol, J.; Pinnock, H.; Ryan, D.; Sheikh, A.; Walker, S.; Williams, S.; Becker, S.; Klimek, L.; Pfaar, O.; Bergmann, K. C.; Mosges, R.; Zuberbier, T.; Roller-Wirnsberger, R. E.; Tomazic, P. V.; Haahtela, T.; Salimaki, J.; Toppila-Salmi, S.; Valovirta, E.; Vasankari, T.; Gemicioglu, B.; Yorgancioglu, A.; Papadopoulos, N. G.; Prokopakis, E. P.; Tsiligianni, I. G.; Bosnic-Anticevich, S.; O'Hehir, R.; Ivancevich, J. C.; Neffen, H.; Zernotti, M. E.; Kull, I.; Melen, E.; Wickman, M.; Bachert, C.; Hellings, P. W.; Brusselle, G.; Palkonen, S.; Bindslev-Jensen, C.; Eller, E.; Waserman, S.; Boulet, L. P.; Bouchard, J.; Chu, D. K.; Schunemann, H. J.; Sova, M.; De Vries, G.; Van Eerd, M.; Agache, I.; Ansotegui, I. J.; Bewick, M.; Casale, T.; Dykewick, M.; Ebisawa, M.; Murray, R.; Naclerio, R.; Okamoto, Y.; Wallace, D. V.; Aberer, W.; Akdis, C. A.; Akdis, M.; Aliberti, M. R.; Almeida, R.; Amat, F.; Angles, R.; Arnavielle, S.; Asayag, E.; Asarnoj, A.; Arshad, H.; Avolio, F.; Bacci, E.; Baiardini, I.; Barbara, C.; Barbagallo, M.; Baroni, I.; Barreto, B. A.; Basagana, X.; Bateman, E. D.; Bedolla-Barajas, M.; Beghe', B.; Bel, E. H.; Bennoor, K. S.; Benson, M.; Bertorello, L.; Bialoszewski, A. Z.; Bieber, T.; Bialek, S.; Bjermer, L.; Blasi, F.; Blua, A.; Bochenska Marciniak, M.; Bogus-Buczynska, I.; Boner, A. L.; Bonini, M.; Bonini, S.; Bourret, R.; Braido, F.; Briedis, V.; Brightling, C. E.; Brozek, J.; Bucca, C.; Buhl, R.; Buonaiuto, R.; Panaitescu, C.; Burguete Cabanas, M. T.; Burte, E.; Bush, A.; Caballero-Fonseca, F.; Caillaud, D.; Caimmi, D.; Calderon, M. A.; Camargos, P. A. M.; Camuzat, T.; Canfora, G.; Carlsen, K. H.; Carreiro-Martins, P.; Carriazo, A. M.; Carr, W.; Cartier, C.; Castellano, G.; Cepeda, A. M.; Chen, Y.; Chiron, R.; Chivato, T.; Chkhartishvili, E.; Chuchalin, A. G.; Chung, K. F.; Ciaravolo, M. M.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Carvalho Coehlo, A. C.; Colas, L.; Colgan, E.; Coll, J.; Conforti, D.; De Sousa, J. C.; Cortes-Grimaldo, R. M.; Corti, F.; Costa-Dominguez, M. C.; Courbis, A. L.; Cox, L.; Crescenzo, M.; Custovic, A.; Dahlen, S. E.; D'Amato, G.; Dario, C.; Darsow, U.; De Blay, F.; De Carlo, G.; Dedeu, T.; De Fatima Emerson, M.; De Martino, B.; Motta Rubina, N. P.; Deleanu, D.; Demoly, P.; Denburg, J. A.; Di Capua Ercolano, S.; Di Carluccio, N.; Didier, A.; Dokic, D.; Dominguez-Silva, M. G.; Douagui, H.; Dray, G.; Durham, S. R.; Du Toit, G.; Dykewicz, M. S.; El-Gamal, Y.; Eklund, P.; Farrell, J.; Farsi, A.; Ferreira De Mello, J.; Ferrero, J.; Fink-Wagner, A.; Fiocchi, A.; Forti, S.; Fuentes-Perez, J. M.; Galvez-Romero, J. L.; Gamkrelidze, A.; Garcia-Aymerich, J.; Garcia-Cobas, C. Y.; Garcia-Cruz, M. H.; Genova, S.; Christoff, G.; Gereda, J. E.; Gerth Van Wijk, R.; Gomez, R. M.; Gomez-Vera, J.; Gonzalez Diaz, S.; Gotua, M.; Grisle, I.; Guidacci, M.; Guldemond, N. A.; Gutter, Z.; Guzman, M. A.; Hajjam, J.; Hernandez, L.; Hourihane, J. O. B.; Humbert, M.; Iaccarino, G.; Ispayeva, Z.; Jares, E. J.; Jassem, E.; Johnston, S. L.; Joos, G.; Jung, K. S.; Just, J.; Jutel, M.; Kaidashev, I.; Kalayci, O.; Kalyoncu, A. F.; Karjalainen, J.; Kardas, P.; Keil, T.; Keith, P. K.; Khaitov, M.; Khaltaev, N.; Kleine-Tebbe, J.; Kowalski, M
abstract

Aims: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. Methods: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. Stakeholders: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. Results: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU grants (2018): MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). Lessons learnt: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

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 - Significant chronic airway abnormalities in never-smoking HIV-infected patients [Articolo su rivista]
Besutti, G.; Santoro, A.; Scaglioni, R.; Neri, S.; Zona, S.; Malagoli, A.; Orlando, G.; Beghe, B.; Ligabue, G.; Torricelli, P.; Manfredini, M.; Pellacani, G.; Fabbri, L. M.; Guaraldi, G.
abstract

Objectives The aim of the study was to describe chronic lung disease in HIV-infected never-smokers by looking at clinical, structural and functional abnormalities. Methods This comparative cross-sectional study included 159 HIV-infected never-smoking patients [mean (+/- standard deviation) age 54.6 +/- 9.1 years; 13.2% female; 98.1% with undetectable viral load] and 75 nonmatched never-smoking controls [mean (+/- standard deviation) age 52.6 +/- 6.9 years; 46.7% female]. We examined calcium scoring computer tomography (CT) scans or chest CT scans, all with a lung-dedicated algorithm reconstruction, to assess emphysema and airway disease (respiratory bronchiolitis and/or bronchial wall thickening), tested pulmonary function using spirometry, lung volumes and the diffusion lung capacity of carbon monoxide (DLCO), and assessed respiratory symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT). Results Twenty-five (17.2%) of the HIV-infected patients versus two (2.7%) of the controls had a CAT score > 10. Only 5% of the HIV-infected patients showed FEV1% < 80%, and 25% had DLCO CT scans, they had increased prevalences, compared with the controls, of airway disease (37% versus 7.9%, respectively) and emphysema (18% versus 4%, respectively), with more severe and more frequent centrilobular disease. After correction for age, sex and clinical factors, HIV infection was significantly associated with CAT > 10 [odds ratio (OR) 7.7], emphysema (OR 4), airway disease (OR 4.5) and DLCO < 75% of predicted (OR 4). Conclusions Although comparisons were limited by the different enrolment methods used for HIV-infected patients and controls, the results suggest that never-smoking HIV-infected patients may present with chronic lung damage characterized by CT evidence of airway disease. A minority of them showed respiratory symptoms, without significant functional abnormalities.

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 - Blood eosinophils for the management of COPD patients? [Articolo su rivista]
Fabbri, L. M.; Beghe', B.; Papi, A.
abstract

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 - Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. [Articolo su rivista]
Schuetz, Philipp; Wirz, Yannick; Sager, Ramon; Christ-crain, Mirjam; Stolz, Daiana; Tamm, Michael; Bouadma, Lila; Luyt, Charles E.; Wolff, Michel; Chastre, Jean; Tubach, Florence; Kristoffersen, Kristina B.; Burkhardt, Olaf; Welte, Tobias; Schroeder, Stefan; Nobre, Vandack; Wei, Long; Bucher, Heiner C.; Annane, Djillali; Reinhart, Konrad; Falsey, Ann R.; Branche, Angela; Damas, Pierre; Nijsten, Maarten; De Lange, Dylan W.; Deliberato, Rodrigo O.; Oliveira, Carolina F.; Maravić-stojković, Vera; Verduri, Alessia; Beghe', Bianca; Cao, Bin; Shehabi, Yahya; Jensen, Jens-ulrik S.; Corti, Caspar; Van Oers, Jos A. H.; Beishuizen, Albertus; Girbes, Armand R. J.; De Jong, Evelien; Briel, Matthias; Muelle, Beat
abstract

BACKGROUND: In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings. METHODS: Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects. FINDINGS: We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (pinteractions>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001). INTERPRETATION: Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.

2018 - MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence [Articolo su rivista]
Bousquet, J.; Arnavielhe, S.; Bedbrook, A.; Bewick, M.; Laune, D.; Mathieu-dupas, E.; Murray, R.; Onorato, G. L.; Pepin, J. L.; Picard, R.; Portejoie, F.; Costa, E.; Fonseca, J.; Lourenco, O.; Morais-Almeida, M.; Todo-bom, A.; Cruz, A. A.; Silva, J. D.; Serpa, F. S.; Illario, M.; Menditto, E.; Cecchi, L.; Monti, R.; Napoli, L.; Ventura, M. T.; De Feo, G.; Larenas-linnemann, D.; Fuentes Perez, M.; Huerta Villabolos, Y. R.; Rivero-yeverino, D.; Rodriguez-zagal, E.; Amat, F.; Annesi-maesano, I.; Bosse, I.; Demoly, P.; Devillier, P.; Fontaine, J. F.; Just, J.; Kuna, T. P.; Samolinski, B.; Valiulis, A.; Emuzyte, R.; Kvedariene, V.; Ryan, D.; Sheikh, A.; Schmidt-grendelmeier, P.; Klimek, L.; Pfaar, O.; Bergmann, K. C.; Mosges, R.; Zuberbier, T.; Roller-wirnsberger, R. E.; Tomazic, P.; Fokkens, W. J.; Chavannes, N. H.; Reitsma, S.; Anto, J. M.; Cardona, V.; Dedeu, T.; Mullol, J.; Haahtela, T.; Salimaki, J.; Toppila-Salmi, S.; Valovirta, E.; Gemicioglu, B.; Yorgancioglu, A.; Papadopoulos, N.; Prokopakis, E. P.; Bosnic-anticevich, S.; O'Hehir, R.; Ivancevich, J. C.; Neffen, H.; Zernotti, E.; Kull, I.; Melen, E.; Wickman, M.; Bachert, C.; Hellings, P.; Palkonen, S.; Bindslev-jensen, C.; Eller, E.; Waserman, S.; Sova, M.; De Vries, G.; van Eerd, M.; Agache, I.; Casale, T.; Dykewickz, M.; Naclerio, R. N.; Okamoto, Y.; Wallace, D. V.; Hellings, P. W.; Aberer, W.; Akdis, C. A.; Akdis, M.; Alberti, M. R.; Almeida, R.; Angles, R.; Ansotegui, I. J.; Arnavielle, S.; Asayag, E.; Asarnoj, A.; Arshad, H.; Avolio, F.; Bacci, E.; Baiardini, I.; Barbara, C.; Barbagallo, M.; Baroni, I.; Barreto, B. A.; Basagana, X.; Bateman, E. D.; Bedolla-Barajas, M.; Beghe', B.; Bel, E. H.; Bennoor, K. S.; Benson, M.; Bertorello, L.; Bialoszewski, A. Z.; Bieber, T.; Bialek, S.; Bjermer, L.; Blain, H.; Blasi, F.; Blua, A.; Bochenska Marciniak, M.; Bogus-Buczynska, I.; Boner, A. L.; Bonini, M.; Bonini, S.; Bosnic-Anticevich, C. S.; Bouchard, J.; Boulet, L. P.; Bourret, R.; Bousquet, P. J.; Braido, F.; Briedis, V.; Brightling, C. E.; Brozek, J.; Bucca, C.; Buhl, R.; Buonaiuto, R.; Panaitescu, C.; Burguete Cabanas, M. T.; Burte, E.; Bush, A.; Caballero-Fonseca, F.; Caillot, D.; Caimmi, D.; Calderon, M. A.; Camargos, P. A. M.; Camuzat, T.; Canfora, G.; Canonica, G. W.; Carlsen, K. H.; Carreiro-Martins, P.; Carriazo, A. M.; Carr, W.; Cartier, C.; Castellano, G.; Cepeda, A. M.; Chen, Y.; Chiron, R.; Chivato, T.; Chkhartishvili, E.; Chuchalin, A. G.; Chung, K. F.; Ciaravolo, M. M.; Ciceran, A.; Cingi, C.; Ciprandi, G.; Carvalho Coehlo, A. C.; Colas, L.; Colgan, E.; Coll, J.; Conforti, D.; Correia de Sousa, J.; Cortes-Grimaldo, R. M.; Corti, F.; Costa-Dominguez, M. C.; Courbis, A. L.; Cox, L.; Crescenzo, M.; Custovic, A.; Czarlewski, W.; Dahlen, S. E.; Dario, C.; da Silva, J.; Dauvilliers, Y.; Darsow, U.; De Blay, F.; De Carlo, G.; de Fatima Emerson, M.; De Martino, B.; de Paula Motta Rubini, N.; Deleanu, D.; Denburg, J. A.; Di Capua Ercolano, S.; Di Carluccio, N.; Didier, A.; Dokic, D.; Dominguez-Silva, M. G.; Douagui, H.; Dray, G.; Dubakiene, R.; Durham, S. R.; Du Toit, G.; Dykewicz, M. S.; El-Gamal, Y.; Eklund, P.; Farrell, J.; Farsi, A.; Ferreira de Mello, J.; Ferrero, J.; Fink-Wagner, A.; Fiocchi, A.; Fonseca, J. A.; Forti, S.; Fuentes-Perez, J. M.; Galvez-Romero, J. L.; Gamkrelidze, A.; Garcia-Aymerich, J.; Garcia-Cobas, C. Y.; Garcia-Cruz, M. H.; Genova, S.; George, C.; Gereda, J. E.; Gerth van Wijk, R.; Gomez, R. M.; Gomez-Vera, J.; Gonzalez Diaz, S.; Gotua, M.; Grisle, I.; Guidacci, M.; Guldemond, N. A.; Gutter, Z.; Guzman, M. A.; Hajjam, J.; Hernandez, L.; Hourihane, J. O. '. B.; Huerta-Villalobos, Y. R.; Humbert, M.; Iaccarino, G.; Jares, E. J.; Jassem, E.; Johnston, S. L.; Joos, G.; Jung, K. S.; Jutel, M.; Kaidashev, I.; Kalayci, O.; Kalyoncu, A. F.; Karjalainen, J.; Kardas, P.; Keil, T.; Keith, P. K.; Khaitov, M.; Khaltaev, N.; Kleine-Tebbe, J.; Kowalski, M. L.; Kuitunen, M.; Kuna, P.; Kupczyk, M.; Krzych-Falta, E.; Lacwik, P.; Lauri, D.; Lavrut, J.; Le, L. T. T
abstract

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

2018 - Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials [Articolo su rivista]
Schuetz, P.; Bolliger, R.; Merker, M.; Christ-Crain, M.; Stolz, D.; Tamm, M.; Luyt, C. E.; Wolff, M.; Schroeder, S.; Nobre, V.; Reinhart, K.; Branche, A.; Damas, P.; Nijsten, M.; Deliberato, R. O.; Verduri, A.; Beghe', B.; Cao, B.; Shehabi, Y.; Jensen, J. -U. S.; Beishuizen, A.; de Jong, E.; Briel, M.; Welte, T.; Mueller, B.
abstract

Introduction: Although evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types. Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients). Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.

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 - We Have to Learn to Do Without Knowing Enough: Anti-Eosinophilic Treatments for Severe Asthma [Articolo su rivista]
Papi, A1; Beghe', Bianca; Fabbri, Lm3; 4,
abstract

Interleukin.5 (IL.5) is the main eosinophilic cytokine that promotes the differentiation, survival, and activation of eosinophils, which are the key inflammatory cells in severe eosinophilic asthma .Thus, it is no surprise that anti.IL.5 pathways have been explored for several years for their ability to reduce eosinophilic inflammation and thus to improve the treatment of this disease.

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 - Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)(Clin Transl Allergy (2016) 6 (29) DOI: 10.1186/s13601-016-0116-9) [Articolo su rivista]
Beghe, Bianca
abstract

[This corrects the article DOI: 10.1186/s13601-016-0116-9.].

2017 - Genetica delle malattie respiratorie. [Capitolo/Saggio]
Beghe', Bianca; Ricciardolo, Fabio; Spagnolo, Paolo
abstract

Nel capitolo sono trattate le principali patologie respiratoria nella cui patogenesi contribuisco fattori genetici. In particolare vengono trattate: fibrosi cistica, asma bronchiale, broncopneumopatia crnica ostrutiiva ( BPCO), e le interstiziopatie polmonari.

2017 - Peripheral eosinophil count as a biomarker for the management of COPD: not there yet. [Articolo su rivista]
Rabe, Klaus F.; Beghe', Bianca; Fabbri, Leonardo M.
abstract

Chronic obstructive pulmonary disease (COPD) is associated with acute and chronic pulmonary as well as systemic inflammation [1]. Anti-inflammatory treatments, such as inhaled corticosteroids (ICS) and oral roflumilast, are recommended for COPD patients [2]. These drugs are effective agents for the prevention of COPD exacerbations and improvement of lung function and have various effects on health status, but they are associated with adverse events, the most concerning being pneumonia (ICS) and diarrhoea (roflumilast).

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

Non disponibile

2017 - Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement. [Articolo su rivista]
Aberer, W; Agache, I; Akdis, Ca; Akdis, M; Alobid, I; Ankri, J; Annesi Maesano, I; Ansotegui, Ij; Anto, Jm; Arnavielhe, S; Arshad, H; Asarnoj, A; Avolio, F; Bachert, C; Bachert, C; Baiardini, I; Barbagallo, M; Barbara, C; Baroody, F; Bateman, Ed; Bedbrook, A; Beghe', Bianca; Bel, Eh; Bennoor, Ks; Benson, M; Bergmann, Kc; Bewick, M; Bialoszewski, Az; Bieber, T; Bindslev Jensen, C; Bjermer, L; Blain, H; Blasi, F; Boner, Al; Bonini, M; Bonini, S; Bosnic Anticevich, S; Bosse, I; Bouchard, J; Boulet, Lp; Bourret, R; Bousquet, J; Bousquet, Pj; Braido, F; Briggs, Ah; Brightling, Ce; Brozek, J; Bucca, C; Buhl, R; Bunu, C; Burte, E; Bush, A; Caballero Fonseca, F; Caimmi, Dp; Calderon, Ma; Camargos, Pa; Camuzat, T; Canonica, Gw; Cardona, V; Carlsen, Kh; Carr, W; Carreiro Martins, P; Carriazo, Am; Casale, T; Cepeda Sarabia, Am; Cervin, A; Cesari, M; Chatzi, L; Chavannes, Nh; Chiron, R; Chivato, T; Chkhartishvili, E; Chuchalin, Ag; Chung, Kf; Ciprandi, G; Cohen, N; Conzález Diaz, S; Cox, L; Crooks, G; Cruz, Aa; Custovic, A; Dahl, R; Dahlen, Se; Darsow, U; De Carlo, G; De Manuel Keenoy, E; de Sousa, Jc; De Vries, G; Dedeu, T; Deleanu, D; Demoly, P; Denburg, Ja; Devillier, P; Didier, A; Dinh Xuan, At; Dokic, D; Douagui, H; Douglas, R; Dray, G; Du Toit, G; Dubakiene, R; Durham, Sr; Dykewicz, Ms; Eklund, P; El Gamal, Y; Ellers, E; Emuzyte, R; Farrell, J; Fink Wagner, A; Fiocchi, A; Fletcher, M; Fokkens, Wj; Fonseca, J; Forastiere, F; Gaga, M; Gamkrelidze, A; Gemicioğlu, B; Georgalas, C; Gereda, Je; Gevaert, P; Goossens, H; Grisle, I; Guldemond, Na; Gutter, Z; Guzmán, Ma; Haahtela, T; Harvey, R; Heinrich, J; Hellings, Pw; Hellings, Pw; Hellquist Dahl, B; Hopkins, C; Horak, F; Hourihane, Jo; Humbert, M; Hyland, M; Iaccarino, G; Illario, M; Jares, Ej; Jeandel, C; Johnston, Sl; Jonquet, O; Joos, G; Joos, G; Jung, Ks; Just, J; Jutel, M; Kaidashev, I; Kalayci, O; Kalogjera, L; Kalyoncu, Af; Kardas, P; Keil, T; Keith, Pk; Kerkhof, M; Kern, B; Kerstjens, Ha; Khaitov, M; Khaltaev, N; Klimek, L; Kogevinas, M; Kolek, V; Koppelman, Gh; Kowalski, M; Kowalski, Ml; Kuitunen, M; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Larenas Linnemann, D; Lau, S; Laune, D; Le, Lt; Li, J; Lieberman, P; Lipworth, B; Lodrup Carlsen, Kc; Louis, R; Lund, Vj; Lupinek, C; MacNee, W; Magar, Y; Magnan, A; Mahboub, B; Maier, D; Majer, I; Malva, J; Manning, P; Marshall, Gd; Masjedi, Mr; Mathieu Dupas, E; Maurer, M; Mavale Manuel, S; Melén, E; Melo Gomes, E; Meltzer, Eo; Mercier, J; Merk, H; Miculinic, N; Mihaltan, F; Milenkovic, B; Millot Keurinck, J; Mohammad, Y; Momas, I; Morais Almeida, M; Mösges, R; Mullol, J; Mullol, J; Muraro, A; Murray, R; Naclerio, R; Nadif, R; Namazova Baranova, L; Neffen, H; Nekam, K; Nieto, A; Niggemann, B; Nogueira Silva, L; Nogues, M; Nyembue, Td; O'Hehir, Re; Ohta, K; Okamoto, Y; Okubo, K; Olive Elias, M; Ouedraogo, S; Paggiaro, P; Pali Schöll, I; Palkonen, S; Panzner, P; Papadopoulos, Ng; Papi, A; Park, Hs; Passalacqua, G; Pawankar, R; Pedersen, S; Pereira, Am; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Pohl, W; Popov, Ta; Portejoie, F; Postma, D; Potter, P; Poulsen, Lk; Price, D; Price, D; Rabe, Kf; Raciborski, F; Riechelmann, H; Robalo Cordeiro, C; Roberts, G; Rodenas, F; Rodriguez Mañas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado Pinto, J; Rosario, N; Rottem, M; Ryan, D; Samolinski, B; Sanchez Borges, M; Sastre Dominguez, J; Scadding, Gk; Schlosser, R; Schmid Grendelmeier, P; Schunemann, Hj; Scichilone, N; Senior, B; Serrano, E; Sheikh, A; Shields, M; Simons, F; Siroux, V; Sisul, Jc; Skrindo, I; Smit, Ha; Solé, D; Sooronbaev, T; Spranger, O; Stellato, C; Stelmach, R; Sterk, Pj; Strandberg, T; Sunyer, J; Thijs, C; Thomas, M; Todo Bom, A; Tomazic, Pv; Toskala, E; Triggiani, M; Valenta, R; Valero, A; Valiulis, A; Valovirta, E; van Eerd, M; van Ganse, E; van Hague, M; van Wick, Rg; Vandenplas, O; Varona, Ll; Vazankari, T; Vellas, B; Ventura, Mt; Vezzani, G; Viegi, G; Voegels, R
abstract

Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.

2017 - Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. [Articolo su rivista]
Schuetz, P; Wirz, Y; Sager, R; Christ-crain, M; Stolz, D; Tamm, M; Bouadma, L; Luyt, Ce; Wolff, M; Chastre, J; Tubach, F; Kristoffersen, Kb; Burkhardt, O; Welte, T; Schroeder, S; Nobre, V; Wei, Licheng; Bucher, Hc; Bhatnagar, N; Annane, D; Reinhart, K; Branche, A; Damas, P; Nijsten, M; De Lange, Dw; Deliberato, Ro; Lima, Ss; Maravić-stojković, V; Verduri, A; Cao, B; Shehabi, Y; Beishuizen, A; Jensen, Js; Corti, C; Van Oers, Ja; Falsey, Ar; De Jong, E; Oliveira, Cf; Beghe, B; Briel, M; Mueller, B.
abstract

BACKGROUND:Acute respiratory infections (ARIs) comprise of a large and heterogeneous group of infections including bacterial, viral, and other aetiologies. In recent years, procalcitonin (PCT), a blood marker for bacterial infections, has emerged as a promising tool to improve decisions about antibiotic therapy (PCT-guided antibiotic therapy). Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with ARIs and different settings ranging from primary care settings to emergency departments, hospital wards, and intensive care units. However, the effect of using procalcitonin on clinical outcomes is unclear. This is an update of a Cochrane review and individual participant data meta-analysis first published in 2012 designed to look at the safety of PCT-guided antibiotic stewardship. OBJECTIVES:The aim of this systematic review based on individual participant data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, and Embase, in February 2017, to identify suitable trials. We also searched ClinicalTrials.gov to identify ongoing trials in April 2017. SELECTION CRITERIA: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm (PCT-guided antibiotic stewardship algorithm) or usual care. We excluded trials if they focused exclusively on children or used procalcitonin for a purpose other than to guide initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS:Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days, for which definitions were harmonised among trials. Secondary endpoints were antibiotic use, antibiotic-related side effects, and length of hospital stay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression adjusted for age, gender, and clinical diagnosis using a fixed-effect model. The different trials were added as random-effects into the model. We conducted sensitivity analyses stratified by clinical setting and type of ARI. We also performed an aggregate data meta-analysis.MAIN RESULTS:From 32 eligible RCTs including 18 new trials for this 2017 update, we obtained individual participant data from 26 trials including 6708 participants, which we included in the main individual participant data meta-analysis. We did not obtain individual participant data for four trials, and two trials did not include people with confirmed ARIs. According to GRADE, the quality of the evidence was high for the outcomes mortality and antibiotic exposure, and quality was moderate for the outcomes treatment failure and antibiotic-related side effects.Primary endpoints: there were 286 deaths in 3336 procalcitonin-guided participants (8.6%) compared to 336 in 3372 controls (10.0%), resulting in a significantly lower mortality associated with procalcitonin-guided therapy (adjusted OR 0.83, 95% CI 0.70 to 0.99, P = 0.037). We could not estimate mortality in primary care trials because only one death was reported in a control group participant. Treatment failure was not significantly lower in procalcitonin-guided participants (23.0% versus 24.9% in the control group, adjusted OR 0.90, 95% CI 0.80 to 1.01, P = 0.068). Results were similar among subgroups by clinical setting and type of respiratory infection, with no evidence for effect modification (P for interaction > 0.05). Secondary endpoints: procalcitonin guidanc

2017 - Triple therapy for symptomatic patients with COPD [Articolo su rivista]
Fabbri, Lm; Roversi, S; Beghé, B.
abstract

Combination therapy is almost the standard for treating chronic diseases, including chronic obstructive pulmonary disease (COPD). Until 2016, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendation for highly symptomatic COPD patients at risk of exacerbations or severe airflow limitation (GOLD D) was treatment with either long-acting muscarinic antagonists (LAMA) or long-acting β2-agonists (LABA) in combination with inhaled glucocorticosteroids (ICS), both with strong evidence. Triple therapy with LAMA/LABA/ICS was also recommended, but with panel consensus judgment, that is, based upon expert opinion only. To our knowledge, no properly powered and sufficiently long randomised clinical trial has ever shown that triple therapy is superior to LAMA, LABA/LAMA, or LABA/ ICS in reducing exacerbations as the primary outcome. However, one short study assessing lung function showed a significant reduction in exacerbations by triple therapy compared with LABA/ICS at 3 months.

2017 - Update in Asthma 2016 [Articolo su rivista]
Beghe', Bianca; Fabbri Leonardo, Michele; Contoli, Marco; Papi, Alberto
abstract

This manuscript reviews the several papers that have been published in 2016 about asthma and particularly severe asthma.

2016 - ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle [Articolo su rivista]
Bousquet, J; Hellings, Pw; Agache, I; Bedbrook, A; Bachert, C; Bergmann, Kc; Bewick, M; Bindslev-jensen, C; Bosnic-anticevitch, S; Bucca, C; Caimmi, Dp; Camargos, Pa; Canonica, Gw; Casale, T; Chavannes, Nh; Cruz, Aa; De Carlo, G; Dahl, R; Demoly, P; Devillier, P; Fonseca, J; Fokkens, Wj; Guldemond, Na; Haahtela, T; Illario, M; Just, J; Keil, T; Klimek, L; Kuna, P; Larenas-linnemann, D; Morais-almeida, M; Mullol, J; Murray, R; Naclerio, R; O'Hehir, Re; Papadopoulos, Ng; Pawankar, R; Potter, P; Ryan, D; Samolinski, B; Schunemann, HOLGER JENS; Sheikh, A; Simons, Fe; Stellato, C; Todo-bom, A; Tomazic, Pv; Valiulis, A; Valovirta, E; Ventura, Mt; Wickman, M; Young, I; Yorgancioglu, A; Zuberbier, T; Aberer, W; Akdis, Ca; Akdis, M; Annesi-maesano, I; Ankri, J; Ansotegui, Ij; Anto, Jm; Arnavielhe, S; Asarnoj, A; Arshad, H; Avolio, F; Baiardini, I; Petrelli, BARBARA CAROLINE; Barbagallo, M; Bateman, Ed; Beghé, B; Bel, Eh; Bennoor, Ks; Benson, M; Białoszewski, Az; Bieber, T; Bjermer, L; Blain, H; Blasi, F; Boner, Al; Bonini, Maria Teresa; Bonini, S; Bosse, I; Bouchard, J; Boulet, Lp; Bourret, R; Bousquet, Pj; Braido, F; Briggs, Ah; Brightling, Ce; Brozek, J; Buhl, R; Bunu, C; Burte, E; Bush, A; Caballero-fonseca, F; Calderon, Ma; Camuzat, T; Cardona, V; Carreiro-martins, P; Carriazo, Am; Carlsen, Kh; Carr, W; Cepeda Sarabia, Am; Cesari, M; Chatzi, L; Chiron, R; Chivato, T; Chkhartishvili, E; Chuchalin, Ag; Chung, Kf; Ciprandi, G; De Sousa, Jc; Cox, L; Crooks, G; Custovic, A; Dahlen, Se; Darsow, U; Dedeu, T; Deleanu, D; Denburg, Ja; De Vries, G; Didier, A; Dinh-xuan, At; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, Sr; Du Toit, G; Dykewicz, Ms; Eklund, P; El-gamal, Y; Ellers, E; Emuzyte, R; Farrell, J; Fink Wagner, A; Fiocchi, Alessandro; Fletcher, M; Forastiere, F; Gaga, M; Gamkrelidze, A; Gemicioğlu, B; Gereda, Je; Van Wick, Rg; González Diaz, S; Grisle, I; Grouse, L; Gutter, Z; Guzmán, Ma; Hellquist-dahl, B; Heinrich, J; Horak, F; Hourihane, Jo; Humbert, M; Hyland, M; Iaccarino, G; Jares, Ej; Jeandel, C; Johnston, Sl; Joos, G; Jonquet, O; Jung, Ks; Jutel, M; Kaidashev, I; Khaitov, M; Kalayci, O; Kalyoncu, Af; Kardas, P; Keith, Pk; Kerkhof, M; Kerstjens, Ha; Khaltaev, N; Kogevinas, M; Kolek, V; Koppelman, Gh; Kowalski, Ml; Kuitunen, M; Kull, I; Kvedariene, V; Lambrecht, B; Lau, S; Laune, D; Le, Lt; Lieberman, P; Lipworth, B; Li, J; Lodrup Carlsen, Kc; Louis, R; Lupinek, C; Macnee, W; Magar, Y; Magnan, A; Mahboub, B; Maier, CARMEN DANIELA; Majer, I; Malva, J; Manning, P; De Manuel Keenoy, E; Marshall, Gd; Masjedi, Mr; Mathieu-dupas, E; Maurer, M; Mavale-manuel, S; Melén, E; Melo-gomes, E; Meltzer, Eo; Mercier, J; Merk, H; Miculinic, N; Mihaltan, F; Milenkovic, B; Millot-keurinck, J; Mohammad, Y; Momas, I; Mösges, R; Muraro, A; Namazova-baranova, L; Nadif, R; Neffen, H; Nekam, K; Nieto, A; Niggemann, B; Nogueira-silva, L; Nogues, M; Nyembue, Td; Ohta, K; Okamoto, Y; Okubo, K; Olive-elias, M; Ouedraogo, S; Paggiaro, P; Pali-schöll, I; Palkonen, S; Panzner, P; Papi, Alice; Park, Hs; Passalacqua, G; Pedersen, S; Pereira, Am; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Pohl, W; Popov, Ta; Portejoie, F; Postma, D; Poulsen, Lk; Price, D; Rabe, Kf; Raciborski, F; Roberts, G; Robalo-cordeiro, C; Rodenas, F; Rodriguez-mañas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado-pinto, J; Rosario, N; Rottem, M; Sanchez-borges, M; Sastre-dominguez, J; Scadding, Gk; Scichilone, N; Schmid-grendelmeier, P; Serrano, E; Shields, M; Siroux, V; Sisul, Jc; Skrindo, I; Smit, Ha; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, Pj; Strandberg, T; Sunyer, J; Thijs, C; Triggiani, M; Valenta, R; Valero, A; Van Eerd, M; Van Ganse, E; Van Hague, M; Vandenplas, O; Varona, Ll; Vellas, B; Vezzani, Gloria; Vazankari, T; Viegi, G; Vontetsianos, T; Wagenmann, M; Walker, S; Wang, Dy; Wahn, U; Werfel, T; Whalley, B; Williams, Dm; Williams, S; Wilson, N; Wright, J; Yawn, Bp; Yiallouros, Pk; Yusuf, O
abstract

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

2016 - MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis [Articolo su rivista]
Bousquet, Jean; Schünemann, Holger J.; Hellings, Peter W.; Arnavielhe, Sylvie; Bachert, Claus; Bedbrook, Anna; Bergmann, Karl Christian; Bosnic Anticevich, Sinthia; Brozek, Jan; Calderon, Moises; Canonica, G. Walter; Casale, Thomas B.; Chavannes, Niels H.; Cox, Linda; Chrystyn, Henry; Cruz, Alvaro A.; Dahl, Ronald; De Carlo, Giuseppe; Demoly, Pascal; Devillier, Phillipe; Dray, Gérard; Fletcher, Monica; Fokkens, Wytske J.; Fonseca, Joao; Gonzalez Diaz, Sandra N.; Grouse, Lawrence; Keil, Thomas; Kuna, Piotr; Larenas Linnemann, Désirée; Lodrup Carlsen, Karin C.; Meltzer, Eli O.; Mullol, Jaoquim; Muraro, Antonella; Naclerio, Robert N.; Palkonen, Susanna; Papadopoulos, Nikolaos G.; Passalacqua, Giovanni; Price, David; Ryan, Dermot; Samolinski, Boleslaw; Scadding, Glenis K.; Sheikh, Aziz; Spertini, François; Valiulis, Arunas; Valovirta, Erkka; Walker, Samantha; Wickman, Magnus; Yorgancioglu, Arzu; Haahtela, Tari; Zuberbier, Torsten; Aberer, Werner; Adachi, Mitsuru; Agache, Ioana; Akdis, Cezmi; Akdis, Mubeccel; Annesi Maesano, Isabella; Ansotegui, Ignacio J.; Anto, Josep M.; Arshad, S. Hasan; Baiardini, Ilaria; Baigenzhin, Abay K.; Barbara, Cristina; Bateman, Eric D.; Beghe', Bianca; Bel, Elisabeth H.; Ben Kheder, Ali; Bennoor, Kazi S.; Benson, Michael; Bernstein, David; Michael, Bewick; Thomas, Bieber; Bindslev Jensen, Carsten; Bjermer, Leif; Blain, Hubert; Boner, Attilio; Bonini, Matteo; Bonini, Sergio; Bosse, Isabelle; Bouchard, Jacques; Boulet, Louis Philippe; Bourret, Rodolphe A.; Bousquet, Philippe J.; Braido, Fulvio; Briggs, Andrew H.; Brightling, Christopher E.; Buhl, Roland; Burney, Peter; Bush, Andrew; Caballero Fonseca, Fernando; Caimmi, Davide P.; Camargos, Paulo; Camuzat, Thierry; Carlsen, Kai Hakon; Carr, Warner; Casale, Thomas B.; Sarabia, Alfonso Cepeda; Chatzi, Leda; Chen, Yuzhi; Chiron, Raphaël; Chkhartishvili, Ekaterine; Chuchalin, Alexander; Ciprandi, Georgio; Cirule, Ieva; Correia de Sousa, Jaime; Costa, David; Crooks, George; Custovic, Adnan; Dahlen, Sven Erik; Darsow, Ulf; De Blay, Frédéric; De Manuel Keenoy, Esteban; Dedeu, Tony; Deleanu, Diana; Denburg, Judah; Didier, Alain; Dinh Xuan, Anh Tuan; Dokic, Dejan; Douagui, Habib B.; Dubakiene, Ruta; Durham, Stephen; Dykewicz, Mark; El Gamal, Yehia; Emuzyte, Regina; Fink Wagner, Antje; Fiocchi, Alessandro; Forastiere, Francesco; Gamkrelidze, Amiran; Gemicioğlu, Bilun; Gereda, Jose E.; Gerth van Wijk, Roy; Gotua, Maia; Grisle, Ineta; Guzmán, M. Antonieta; Haahtela, Tari; Heinrich, Joachim; Hellquist Dahl, Birthe; Horak, Friedrich; Howarth, Peter H.; Humbert, Marc; Hyland, Michael; Ivancevich, Juan Carlos; Jares, Edgardo J.; Johnston, Sebastian L.; Jonquet, Olivier; Joos, Guy; Jung, Ki Suck; Just, Jocelyne; Jutel, Marek; Kaidashev, Igor P.; Khaitov, Musa; Kalayci, Omer; Kalyoncu, Fuat; Keith, Paul; Khaltaev, Nikolai; Kleine Tebbe, Jorg; Klimek, Ludger; N'Goran, Bernard Koffi; Kolek, Vitezlav; Koppelman, Gerard H.; Kowalski, Marek; Kull, Inger; Kvedariene, Violeta; Lambrecht, Bart; Lau, Susanne; Laune, Daniel; Le Thi Tuyet, Lan; Li, Jing; Lieberman, Phillipe; Lipworth, Brian J.; Renaud, Louis; Magard, Yves; Magnan, Antoine; Mahboub, Bassam; Majer, Ivan; Makela, Mika; Manning, Peter J.; Masjedi, Mohamad R.; Maurer, Marcus; Mavale Manuel, Sandra; Melén, Erik; Melo Gomes, Elisabete; Mercier, Jacques; Merk, Hans; Miculinic, Neven; Mihaltan, Florin; Milenkovic, Branislava; Mohammad, Yousser; Molimard, Mathieu; Momas, Isabelle; Montilla Santana, Anna; Morais Almeida, Mario; Mösges, Ralph; Nadif, Rachel; Namazova Baranova, Leyla; Neffen, Hugo; Nekam, Kristof; Neou, Angelos; Niggemann, Bodo; Nyembue, Dieudonné; O'Hehir, Robyn; Ohta, Ken; Okamoto, Yoshitaka; Okubo, Kim; Ouedraogo, Solange; Paggiaro, Pier Luigi; Pali Schöll, Isabella; Palmer, Stephen; Panzner, Petr; Papi, Alberto; Park, Hae Sim; Pavord, Ian; Pawankar, Ruby; Pfaar, Oliver; Picard, Robert; Pigearias, Bernard; Pin, Isabelle; Plavec, Davor; Pohl, Wolfgang; Popov, To
abstract

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.

2016 - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) [Articolo su rivista]
Bousquet, J; Farrell, J; Crooks, G; Hellings, P; Bel, E. H; Bewick, M; Chavannes, N. H; de Sousa, J. Correia; Cruz, A. A; Haahtela, T; Joos, G; Khaltaev, N; Malva, J; Muraro, A; Nogues, M; Palkonen, S; Pedersen, S; Robalo Cordeiro, C; Samolinski, B; Strandberg, T; Valiulis, A; Yorgancioglu, A; Zuberbier, T; Bedbrook, A; Aberer, W; Adachi, M; Agusti, A; Akdis, C. A; Akdis, M; Ankri, J; Alonso, A; Annesi Maesano, I; Ansotegui, I. J; Anto, J. M; Arnavielhe, S; Arshad, H; Bai, C; Baiardini, I; Bachert, C; Baigenzhin, A. K; Barbara, C; Bateman, E. D; Beghe', Bianca; Kheder, A. Ben; Bennoor, K. S; Benson, M; Bergmann, K. C; Bieber, T; Bindslev Jensen, C; Bjermer, L; Blain, H; Blasi, F; Boner, A. L; Bonini, M; Bonini, S; Bosnic Anticevitch, S; Boulet, L. P; Bourret, R; Bousquet, P. J; Braido, F; Briggs, A. H; Brightling, C. E; Brozek, J; Buhl, R; Burney, P. G; Bush, A; Caballero Fonseca, F; Caimmi, D; Calderon, M. A; Calverley, P. M; Camargos, P. A. M; Canonica, G. W; Camuzat, T; Carlsen, K. H; Carr, W; Carriazo, A; Casale, T; Cepeda Sarabia, A. M; Chatzi, L; Chen, Y. Z; Chiron, R; Chkhartishvili, E; Chuchalin, A. G; Chung, K. F; Ciprandi, G; Cirule, I; Cox, L; Costa, D. J; Custovic, A; Dahl, R; Dahlen, S. E; Darsow, U; De Carlo, G; De Blay, F; Dedeu, T; Deleanu, D; De Manuel Keenoy, E; Demoly, P; Denburg, J. A; Devillier, P; Didier, A; Dinh Xuan, A. T; Djukanovic, R; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S. R; Dykewicz, M. S; El Gamal, Y; Emuzyte, R; Fabbri, Leonardo; Fletcher, M; Fiocchi, A; Fink Wagner, A; Fonseca, J; Fokkens, W. J; Forastiere, F; Frith, P; Gaga, M; Gamkrelidze, A; Garces, J; Garcia Aymerich, J; Gemicioğlu, B; Gereda, J. E; González Diaz, S; Gotua, M; Grisle, I; Grouse, L; Gutter, Z; Guzmán, M. A; Heaney, L. G; Hellquist Dahl, B; Henderson, D; Hendry, A; Heinrich, J; Heve, D; Horak, F; Hourihane, J. O' B; Howarth, P; Humbert, M; Hyland, M. E; Illario, M; Ivancevich, J. C; Jardim, J. R; Jares, E. J; Jeandel, C; Jenkins, C; Johnston, S. L; Jonquet, O; Julge, K; Jung, K. S; Just, J; Kaidashev, I; Kaitov, M. R; Kalayci, O; Kalyoncu, A. F; Keil, T; Keith, P. K; Klimek, L; Koffi N'Goran, B; Kolek, V; Koppelman, G. H; Kowalski, M. L; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Lau, S; Larenas Linnemann, D; Laune, D; Le, L. T. T; Lieberman, P; Lipworth, B; Li, J; Lodrup Carlsen, K; Louis, R; Macnee, W; Magard, Y; Magnan, A; Mahboub, B; Mair, A; Majer, I; Makela, M. J; Manning, P; Mara, S; Marshall, G. D; Masjedi, M. R; Matignon, P; Maurer, M; Mavale Manuel, S; Melén, E; Melo Gomes, E; Meltzer, E. O; Menzies Gow, A; Merk, H; Michel, J. P; Miculinic, N; Mihaltan, F; Milenkovic, B; Mohammad, G. M. Y; Molimard, M; Momas, I; Montilla Santana, A; Morais Almeida, M; Morgan, M; Mösges, R; Mullol, J; Nafti, S; Namazova Baranova, L; Naclerio, R; Neou, A; Neffen, H; Nekam, K; Niggemann, B; Ninot, G; Nyembue, T. D; O'Hehir, R. E; Ohta, K; Okamoto, Y; Okubo, K; Ouedraogo, S; Paggiaro, P; Pali Schöll, I; Panzner, P; Papadopoulos, N; Papi, A; Park, H. S; Passalacqua, G; Pavord, I; Pawankar, R; Pengelly, R; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Poethig, D; Pohl, W; Popov, T. A; Portejoie, F; Potter, P; Postma, D; Price, D; Rabe, K. F; Raciborski, F; Radier Pontal, F; Repka Ramirez, S; Reitamo, S; Rennard, S; Rodenas, F; Roberts, J; Roca, J; Rodriguez Mañas, L; Rolland, C; Roman Rodriguez, M; Romano, A; Rosado Pinto, J; Rosario, N; Rosenwasser, L; Rottem, M; Ryan, D; Sanchez Borges, M; Scadding, G. K; Schunemann, H. J; Serrano, E; Schmid Grendelmeier, P; Schulz, H; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Simons, F. E. R; Sisul, J. C; Skrindo, I; Smit, H. A; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Sterk, P. J; Sunyer, J; Thijs, C; To, T; Todo Bom, A; Triggiani, M; Valenta, R; Valero, A. L; Valia, E; Valovirta, E; Van Ganse, E; van Hage, M; Vandenplas, O; Vasankari, T; Vellas, B; Vestbo, J; Vezzani, G; Vichyanond, P; Viegi, G
abstract

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

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 - Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: A randomized noninferiority trial [Articolo su rivista]
Verduri, Alessia; Luppi, Fabrizio; D'Amico, Roberto; Balduzzi, Sara; Vicini, Roberto; Liverani, Anna; Ruggieri, Valentina; Plebani, Mario; Barbaro Foschino, Maria Pia; Spanevello, Antonio; Canonica, Giorgio Walter; Papi, Alberto; Fabbri, Leonardo; Beghe', Bianca
abstract

The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD. METHODS AND FINDINGS: We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days. CONCLUSIONS: Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098). TRIAL REGISTRATION: ClinicalTrials.gov NCT01125098.

2015 - Eosinophilia in asthma: the easy way is not always the best [Articolo su rivista]
Beghe', Bianca; Spanevello, Antonio; Fabbri, Leonardo
abstract

In this article the role of eosinophilic inflammation is discussed.

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 - MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation [Articolo su rivista]
Bousquet, J.; Schunemann, H. J.; Fonseca, J.; Samolinski, B.; Bachert, C.; Canonica, G. W.; Casale, T.; Cruz, A. A.; Demoly, P.; Hellings, P.; Valiulis, A.; Wickman, M.; Zuberbier, T.; Bosnic Anticevitch, S.; Bedbrook, A.; Bergmann, K. C.; Caimmi, D.; Dahl, R.; Fokkens, W. J.; Grisle, I.; Lodrup Carlsen, K.; Mullol, J.; Muraro, A.; Palkonen, S.; Papadopoulos, N.; Passalacqua, G.; Ryan, D.; Valovirta, E.; Yorgancioglu, A.; Aberer, W.; Agache, I.; Adachi, M.; Akdis, C. A.; Akdis, M.; Annesi Maesano, I.; Ansotegui, I. J.; Anto, J. M.; Arnavielhe, S.; Arshad, H.; Baiardini, I.; Baigenzhin, A. K.; Barbara, C.; Bateman, E. D.; Beghe', Bianca; Bel, E. H.; Ben Kheder, A.; Bennoor, K. S.; Benson, M.; Bewick, M.; Bieber, T.; Bindslev Jensen, C.; Bjermer, L.; Blain, H.; Boner, A. L.; Boulet, L. P.; Bonini, M.; Bonini, S.; Bosse, I.; Bourret, R.; Bousquet, P. J.; Braido, F.; Briggs, A. H.; Brightling, C. E.; Brozek, J.; Buhl, R.; Burney, P. G.; Bush, A.; Caballero Fonseca, F.; Calderon, M. A.; Camargos, P. A. M.; Camuzat, T.; Carlsen, K. H.; Carr, W.; Cepeda Sarabia, A. M.; Chavannes, N. H.; Chatzi, L.; Chen, Y. Z.; Chiron, R.; Chkhartishvili, E.; Chuchalin, A. G.; Ciprandi, G.; Cirule, I.; Correia De Sousa, J.; Cox, L.; Crooks, G.; Costa, D. J.; Custovic, A.; Dahlen, S. E.; Darsow, U.; De Carlo, G.; De Blay, F.; Dedeu, T.; Deleanu, D.; Denburg, J. A.; Devillier, P.; Didier, A.; Dinh Xuan, A. T.; Dokic, D.; Douagui, H.; Dray, G.; Dubakiene, R.; Durham, S. R.; Dykewicz, M. S.; El Gamal, Y.; Emuzyte, R.; Fink Wagner, A.; Fletcher, M.; Fiocchi, A.; Forastiere, F.; Gamkrelidze, A.; Gemicioʇlu, B.; Gereda, J. E.; González Diaz, S.; Gotua, M.; Grouse, L.; Guzmán, M. A.; Haahtela, T.; Hellquist Dahl, B.; Heinrich, J.; Horak, F.; Hourihane, J. O. B.; Howarth, P.; Humbert, M.; Hyland, M. E.; Ivancevich, J. C.; Jares, E. J.; Johnston, S. L.; Joos, G.; Jonquet, O.; Jung, K. S.; Just, J.; Kaidashev, I.; Kalayci, O.; Kalyoncu, A. F.; Keil, T.; Keith, P. K.; Khaltaev, N.; Klimek, L.; Koffi N'Goran, B.; Kolek, V.; Koppelman, G. H.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Lambrecht, B.; Lau, S.; Larenas Linnemann, D.; Laune, D.; Le, L. T. T.; Lieberman, P.; Lipworth, B.; Li, J.; Louis, R.; Magard, Y.; Magnan, A.; Mahboub, B.; Majer, I.; Makela, M. J.; Manning, P.; De Manuel Keenoy, E.; Marshall, G. D.; Masjedi, M. R.; Maurer, M.; Mavale Manuel, S.; Melén, E.; Melo Gomes, E.; Meltzer, E. O.; Merk, H.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Mohammad, Y.; Molimard, M.; Momas, I.; Montilla Santana, A.; Morais Almeida, M.; Mösges, R.; Namazova Baranova, L.; Naclerio, R.; Neou, A.; Neffen, H.; Nekam, K.; Niggemann, B.; Nyembue, T. D.; O'Hehir, R. E.; Ohta, K.; Okamoto, Y.; Okubo, K.; Ouedraogo, S.; Paggiaro, P.; Pali Schöll, I.; Palmer, S.; Panzner, P.; Papi, A.; Park, H. S.; Pavord, I.; Pawankar, R.; Pfaar, O.; Picard, R.; Pigearias, B.; Pin, I.; Plavec, D.; Pohl, W.; Popov, T. A.; Portejoie, F.; Postma, D.; Potter, P.; Price, D.; Rabe, K. F.; Raciborski, F.; Radier Pontal, F.; Repka Ramirez, S.; Robalo Cordeiro, C.; Rolland, C.; Rosado Pinto, J.; Reitamo, S.; Rodenas, F.; Roman Rodriguez, M.; Romano, A.; Rosario, N.; Rosenwasser, L.; Rottem, M.; Sanchez Borges, M.; Scadding, G. K.; Serrano, E.; Schmid Grendelmeier, P.; Sheikh, A.; Simons, F. E. R.; Sisul, J. C.; Skrindo, I.; Smit, H. A.; Solé, D.; Sooronbaev, T.; Spranger, O.; Stelmach, R.; Strandberg, T.; Sunyer, J.; Thijs, C.; Todo Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Van Hage, M.; Vandenplas, O.; Vezzani, G.; Vichyanond, P.; Viegi, G.; Wagenmann, M.; Walker, S.; Wang, D. Y.; Wahn, U.; Williams, D. M.; Wright, J.; Yawn, B. P.; Yiallouros, P. K.; Yusuf, O. M.; Zar, H. J.; Zernotti, M. E.; Zhang, L.; Zhong, N.; Zidarn, M.; Mercier, J.
abstract

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

2015 - Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial [Articolo su rivista]
Papi, Alberto; Marku, Brunilda; Scichilone, Nicola; Maestrelli, Piero; Paggiaro, Pierluigi; Saetta, Marina; Nava, Stefano; Folletti, Ilenia; Bertorelli, Giuseppina; Bertacco, Stefano; Contoli, Marco; Plebani, Mario; Barbaro Foschino, Maria Pia; Spanevello, Antonio; Aliani, Maria; Pannacci, Marco; Morelli, Paolo; Beghe', Bianca; Fabbri, Leonardo
abstract

BACKGROUND: Treatment guidelines for patients with moderate persistent asthma recommend regular therapy with a combination of an inhaled corticosteroid and a longacting β2 agonist plus as-needed rapid-acting bronchodilators. We investigated whether symptom-driven budesonide and formoterol combination therapy administered as needed would be as effective as regular treatment with this combination plus as-needed symptom-driven terbutaline for patients with moderate asthma. METHODS: In this non-inferiority randomised clinical trial, we recruited adult patients (18-65 years of age) with stable moderate persistent asthma, according to 2006 Global Initiative for Asthma guidelines. Patients were recruited from outpatient clinics of secondary and tertiary referral hospitals and university centres. After a 6-week run-in period of inhaled regular budesonide and formoterol plus as-needed terbutaline, the patients were randomly assigned in a 1:1 ratio to receive placebo twice daily plus as-needed treatment with inhaled 160 μg budesonide and 4·5 μg formoterol (as-needed budesonide and formoterol therapy) or twice-daily 160 μg budesonide and 4·5 μg formoterol combination plus symptom-driven 500 μg terbutaline (regular budesonide/formoterol therapy) for 1 year. Randomisation was done according to a list prepared with the use of a random number generator and a balanced-block design stratified by centre. Patients and investigators were masked to treatment assignment. The primary outcome was time to first treatment failure measured after 1 year of treatment using Kaplan-Meier estimates, and the power of the study was calculated based on the rate of treatment failure. Analyses were done on the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00849095. FINDINGS: Between April 20, 2009, and March 31, 2012, we screened 1010 patients with moderate asthma and randomly assigned 866 eligible patients to the two treatment groups (424 to as-needed budesonide and formoterol therapy and 442 to regular budenoside and formoterol therapy). Compared with regular budesonide and formoterol therapy, as-needed budesonide and formoterol treatment was associated with a lower probability of patients having no treatment failure at 1 year (Kaplan-Meier estimates 53·6% for as-needed treatment vs 64·0% for regular treatment; difference 10·3% [95% CI 3·2-17·4], at a predefined non-inferiority limit of 9%). Patients in the as-needed budesonide and formoterol group had shorter time to first treatment failure than those in the regular therapy group (11·86 weeks vs 28·00 weeks for the first quartile [ie, the time until the first 25% of patients experienced treatment failure]). The difference in treatment failures was largely attributable to nocturnal awakenings (82 patients in the as-needed treatment group vs 44 in the regular treatment group). Both treatment regimens were well tolerated. INTERPRETATION: In patients with moderate stable asthma, as-needed budesonide and formoterol therapy is less effective than is the guideline-recommended regular budesonide and formoterol treatment, even though the differences are small. FUNDING: Italian Medicines Agency

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

Not available

2014 - The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy [Articolo su rivista]
Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Ligabue, Guido; Marchioni, Alessandro; Orlando, Gabriella; Carli, Federica; Beghe', Bianca; Fabbri, Leonardo; J., Leipsic; D., Don Sin; S. F. P., Man
abstract

Abstract Background: With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown. Methods: Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning. Findings: Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction ,.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype. Interpretation: Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.

2013 - Acute exacerbations of chronic obstructive pulmonary disease provide a unique opportunity to take care of patients [Articolo su rivista]
Beghe', Bianca; Garofalo, Martina; Fabbri, Leonardo
abstract

Exacerbation of chronic obstructive pulmonary disease (ECOPD) identifies the acute phase of COPD. The COPD patient is often frail and elderly with concomitant chronic diseases. This requires the physician not only looks at specific symptoms or organs, but to consider the patient in all his or her complexity. ©Copyright B. Beghé et al., 2013 Licensee PAGEPress.

2013 - Asthma [Capitolo/Saggio]
Beghe', Bianca; Fabbri, Leonardo
abstract

Non richiesto

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 - Echocardiography, Spirometry, and Systemic Acute-Phase Inflammatory Proteins in Smokers with COPD or CHF: An Observational Study [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Bottazzi, Barbara; Stendardo, Mariarita; Fucili, Alessandro; Balduzzi, Sara; Leuzzi, Chiara; Papi, Alberto; Mantovani, Alberto; Fabbri, Leonardo; Ceconi, Claudio; Boschetto, Piera
abstract

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1 beta (IL-1 beta), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged >= 50 years and with >= 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 beta, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 beta, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

2013 - Exacerbation of respiratory Symptoms in COPD patients may not be exacerbations of COPD [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Roca, M; Fabbri, Leonardo
abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as acute events characterised by a worsening of the patient's respiratory symptoms, particularly dyspnoea, beyond day-to-day variation, leading to a change in medical treatment and/or hospitalisation. Exacerbations of COPD are a leading cause of hospitalisation and healthcare expenditures, particularly in frail, elderly patients. They alter the health-related quality of life and the natural course of disease, increasing the risk of mortality, both during and after the acute event. Patients with COPD frequently have chronic comorbidities. Several of these comorbidities may produce acute events, contributing to the increased morbidity and mortality in COPD exacerbations: acute myocardial infarction, congestive heart failure, cerebrovascular disease, cardiac arrhythmias and pulmonary circulation disorders.

2013 - Genetica delle malattie respiratorie [Capitolo/Saggio]
Fabbri, Leonardo M.; Marsico, Serafino A.; Beghe', Bianca
abstract

Non previsto

2013 - Identifying and Treating COPD in Cardiac Patients [Articolo su rivista]
Carlo, Nozzoli; Beghe', Bianca; Piera, Boschetto; Fabbri, Leonardo
abstract

2013 - Inhaled Corticosteroids in COPD: Pros and Cons. [Articolo su rivista]
Zervas, E.; Samitas, K.; Gaga, M.; Beghe', Bianca; Fabbri, Leonardo
abstract

Chronic obstructive pulmonary disease (COPD) is a devastating illness characterized by airway and systemic inflammation, progressive airway obstruction and exacerbations. It is a major cause of chronic morbidity and mortality, projected to be the third leading cause of death by the year 2020. Although there is currently no definite cure, COPD is both a preventable and treatable disease. Important changes in our perspective and understanding of the disease have been made that lead to marked improvements in the treatment of COPD, such as the use of long-acting anticholinergics, β2 agonists and inhaled corticosteroids (ICS). Current GOLD guidelines call for the use of ICS in patients with severe and very severe airflow limitation and/or for patients with frequent exacerbations. This population constitutes only around 20% of all COPD patients, however current data show that as much as 70% are prescribed ICS. Although widely used, clinical trials on the efficacy of ICS in COPD have been up to now inconclusive or even contradictory. This has lead to wide confusion and debate regarding their role in the management of COPD. This review summarizes all current knowledge originating from observational studies, randomized clinical trials and expert views regarding ICS therapy in COPD. Arguments in favor and against the use of ICS are presented with respect to airway and systemic inflammation, exacerbation frequency and severity, lung function decline, quality of life, mortality and adverse events

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 - Phosphodiesterase-4 Inhibitor Therapy for Lung Diseases [Articolo su rivista]
Beghe', Bianca; Rabe, Klaus; Fabbri, Leonardo
abstract

Phosphodiesterases (PDEs) are a superfamily of enzymes that catalyze the breakdown of cAMP and/or cyclic guanosine monophosphate (GMP) to their inactive form. PDE4 is the main selective cAMP-metabolizing enzyme in inflammatory and immune cells. Because PDE4 is highly expressed in leukocytes and other inflammatory cells involved in the pathogenesis of inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), inhibition of PDE4 has been predicted to have an antiinflammatory effect and thus therapeutic efficacy. The limited and inconsistent efficacy and side effects of the early compounds made their further development less desirable in asthma, given the excellent efficacy/tolerability ratio of inhaled steroids. The lack of effective antiinflammatory drug treatment for COPD has thus shifted the interest in development toward COPD. Roflumilast, the only PDE4 inhibitor that has reached the market because of the good efficacy/tolerability ratio, is recommended for patients with COPD with severe airflow limitation, symptoms of chronic bronchitis, and a history of exacerbations, whose disease is not adequately controlled by long-acting bronchodilators. Albeit safe, it maintains significant side effects (diarrhea, nausea, weight loss) that make it intolerable in some patients. Future developments of PDE4 inhibitors include extended indications of roflumilast (1) in patients with COPD, and(2) in other respiratory (e. g., asthma) and nonrespiratory chronic inflammatory/metabolic conditions (e. g., diabetes), as well as (3) the development of new molecules with PDE4 inhibitory properties with an improved efficacy/tolerability profile.

2013 - Reply: look at the moon, not just at the finger indicating the moon [Articolo su rivista]
Fabbri, Leonardo; Beghe', Bianca; Agustí, Alvar
abstract

Not available

2012 - Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs [Articolo su rivista]
Bousquet, J; Schünemann, H. J; Samolinski, B; Demoly, P; Baena Cagnani, C. E; Bachert, C; Bonini, S; Boulet, L. P; Bousquet, P. J; Brozek, J. L; Canonica, G. W; Casale, T. B; Cruz, A. A; Fokkens, W. J; Fonseca, J. A; van Wijk, R. Gerth; Grouse, L; Haahtela, T; Khaltaev, N; Kuna, P; Lockey, R. F; Lodrup Carlsen, K. C; Mullol, J; Naclerio, R; O'Hehir, R. E; Ohta, K; Palkonen, S; Papadopoulos, N. G; Passalacqua, G; Pawankar, R; Price, D; Ryan, D; Simons, F. E. R; Togias, A; Williams, D; Yorgancioglu, A; Yusuf, O. M; Aberer, W; Adachi, M; Agache, I; Aït Khaled, N; Akdis, C. A; Andrianarisoa, A; Annesi Maesano, I; Ansotegui, I. J; Baiardini, I; Bateman, E. D; Bedbrook, A; Beghe', Bianca; Beji, M; Bel, E. H; Ben Kheder, A; Bennoor, K. S; Bergmann, K. C; Berrissoul, F; Bieber, T; Bindslev Jensen, C; Blaiss, M. S; Boner, A. L; Bouchard, J; Braido, F; Brightling, C. E; Bush, A; Caballero, F; Calderon, M. A; Calvo, M. A; Camargos, P. A. M; Caraballo, L. R; Carlsen, K. H; Carr, W; Cepeda, A. M; Cesario, A; Chavannes, N. H; Chen, Y. Z; Chiriac, A. M; Chivato Pérez, T; Chkhartishvili, E; Ciprandi, G; Costa, D. J; Cox, L; Custovic, A; Dahl, R; Darsow, U; De Blay, F; Deleanu, D; Denburg, J. A; Devillier, P; Didi, T; Dokic, D; Dolen, W. K; Douagui, H; Dubakiene, R; Durham, S. R; Dykewicz, M. S; El Gamal, Y; El Meziane, A; Emuzyte, R; Fiocchi, A; Fletcher, M; Fukuda, T; Gamkrelidze, A; Gereda, J. E; González Diaz, S; Gotua, M; Guzmán, M. A; Hellings, P. W; Hellquist Dahl, B; Horak, F; Hourihane, J. O'B; Howarth, P; Humbert, M; Ivancevich, J. C; Jackson, C; Just, J; Kalayci, O; Kaliner, M. A; Kalyoncu, A. F; Keil, T; Keith, P. K; Khayat, G; Kim, Y. Y; Koffi N'goran, B; Koppelman, G. H; Kowalski, M. L; Kull, I; Kvedariene, V; Larenas Linnemann, D; Le, L. T; Lemière, C; Li, J; Lieberman, P; Lipworth, B; Mahboub, B; Makela, M. J; Martin, F; Marshall, G. D; Martinez, F. D; Masjedi, M. R; Maurer, M; Mavale Manuel, S; Mazon, A; Melen, E; Meltzer, E. O; Mendez, N. H; Merk, H; Mihaltan, F; Mohammad, Y; Morais Almeida, M; Muraro, A; Nafti, S; Namazova Baranova, L; Nekam, K; Neou, A; Niggemann, B; Nizankowska Mogilnicka, E; Nyembue, T. D; Okamoto, Y; Okubo, K; Orru, M. P; Ouedraogo, S; Ozdemir, C; Panzner, P; Pali Schöll, I; Park, H. S; Pigearias, B; Pohl, W; Popov, T. A; Postma, D. S; Potter, P; Rabe, K. F; Ratomaharo, J; Reitamo, S; Ring, J; Roberts, R; Rogala, B; Romano, A; Roman Rodriguez, M; Rosado Pinto, J; Rosenwasser, L; Rottem, M; Sanchez Borges, M; Scadding, G. K; Schmid Grendelmeier, P; Sheikh, A; Sisul, J. C; Solé, D; Sooronbaev, T; Spicak, V; Spranger, O; Stein, R. T; Stoloff, S. W; Sunyer, J; Szczeklik, A; Todo Bom, A; Toskala, E; Tremblay, Y; Valenta, R; Valero, A. L; Valeyre, D; Valiulis, A; Valovirta, E; Van Cauwenberge, P; Vandenplas, O; van Weel, C; Vichyanond, P; Viegi, G; Wang, D. Y; Wickman, M; Wöhrl, S; Wright, J; Yawn, B. P; Yiallouros, P. K; Zar, H. J; Zernotti, M. E; Zhong, N; Zidarn, M; Zuberbier, T; Burney, P. G; Johnston, S. L; Warner, J. O.
abstract

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

2012 - COPD and the Solar System:Introducing the Chronic Obstructive Pulmonary Disease Comorbidome [Articolo su rivista]
Fabbri, Leonardo; Beghe', Bianca; A., Agustí
abstract

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as the pulmonary component of a more complex syndrome characterized by structural abnormalities of the airways (bronchiolitis) and lung (emphysema), and also by concomitant disorders (comorbidities) such as cardiovascular disease, metabolic syndrome, osteoporosis, depression, cancer, and inflammatory bowel disease. These comorbidities influence not only the severity of the symptoms and the quality of life of individual patients, but also the risk of hospitalization and eventually death. In turn, COPD is a frequent and important comorbidity of these same chronic conditions (e.g., ischemic heart disease, chronic heart failure, arrhythmia, osteoporosis, and metabolic syndrome). Indeed, only a minority of patients with COPD die of respiratory failure; most die of other conditions, particularly cardiovascular disease, pneumonia, thromboembolism, and cancer (mainly lung cancer)

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 - Inhaled corticosteroid and long-acting β2-agonist pharmacological profiles: effective asthma therapy in practice [Articolo su rivista]
Tamm, M; Richards, Dh; Beghe', Bianca; Fabbri, Leonardo
abstract

Fixed-dose combinations of inhaled corticosteroids (ICSs) and long-acting b2-agonists (LABAs) have been used to manage asthma for several years. They are the preferred therapy option for patients who do not achieve optimal control of their asthma with lowdose ICS monotherapy. In Europe, four ICS/LABA products are commercially available for asthma maintenance therapy (fluticasone propionate/formoterol fumarate, fluticasone propionate/salmeterol xinafoate, budesonide/formoterol fumarate and beclometasone dipropionate/formoterol fumarate), and other combinations are likely to be developed over the next few years (e.g. mometasone/formoterol fumarate, fluticasone furoate/ vilanterol, mometasone/indacaterol). Data from randomized, controlled, clinical trials do not demonstrate a clear overall efficacy difference among ICS/LABA combinations approved for asthma therapy. Conversely, pharmacological data indicate that there may be certain advantages to using one ICS or LABA over another because of the specific pharmacodynamic and pharmacokinetic profiles associated with particular treatments. This review article summarizes the pharmacological characteristics of the various ICSs and LABAs available for the treatment of asthma, including the potential for ICS and LABA synergy, and gives an insight into the rationale for the development of the latest ICS/LABA combination approved for asthma maintenance therapy.

2012 - Leukotriene B4 receptor locus gene characterisation and association studies in asthma [Articolo su rivista]
Astulah, A. S. Tulah; Beghe', Bianca; Barton, S. J.; Holloway, J. W.; Sayers, I.
abstract

Polymorphisms spanning genes involved in the production of leukotriene B4 (LTB4) e.g. ALOX5AP and LTA4H are associated with asthma susceptibility, suggesting a role for LTB4 in disease. The contribution of LTB 4 receptor polymorphism is currently unknown. The aim of this study was to characterise the genes for the two pivotal LTB4 receptors, LTB4R1 and LTB4R2 in lung tissue and determine if polymorphisms spanning these genes are associated with asthma and disease severity. Rapid amplification of cDNA ends (RACE) was used to characterise the LTB4R1 and LTB4R2 gene structure in lung. The LTB4R1/2 locus on chromosome 14q11.2 was screened for polymorphic variation. Six LTB4R single nucleotide polymorphisms (SNPs) were genotyped in 370 Caucasian asthma families and 299 Adult Asthma Individuals (n=1877 total) and were evaluated for association with asthma and severity (BTS) outcome measures using Family Based Association Test, linear regression and chi square. LTB4R1 has complex mRNA arrangement including multiple 5?-untranslated exons, suggesting additional levels of regulation. Three potential promoter regions across the LTB4R1/2 locus were identified with some airway cell specificity. 22 SNPs (MAF>0.01) were validated across the LTB4R locus in the Caucasian population. LTB4R1 and LTB4R2 SNPs were not associated with asthma susceptibility, FEV1 or severity. LTB4R1 and LTB4R2 shows splice variation in the 5?-untranslated region and multiple promoter regions. The functional significance of this is yet to be determined. Both receptor genes were shown to be polymorphic. LTB4R polymorphisms do not appear to be susceptibility markers for the development of asthma in Caucasian subjects

2012 - Link between chronic obstructive pulmonary disease and coronary artery disease: implication for clinical practice [Articolo su rivista]
Boschetto, P; Beghe', Bianca; Fabbri, Leonardo; Ceconi, C.
abstract

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are global epidemics that incur significant morbidity and mortality. These diseases are frequently found in combination, and they can also be found independent of the common causal factors, primarily smoking. Both conditions are systemic disorders with overlapping mechanisms and pathophysiologic processes. CAD has a strong effect on the severity and prognosis of COPD and vice versa, including acute exacerbations. Even the most recent practical clinical recommendations driven by Clinical Practice Guidelines still focus on one disease at a time, and do not provide advice for the management of patients with associated chronic conditions. COPD should be approached in a more comprehensive manner, including the treatment of cardiac comorbidities, particularly CAD. To focus treatment on these comorbidities might modify the natural course of the disease in patients with COPD who may not find relief from treatment of COPD alone.

2012 - Malattie respiratorie ostruttive. Bronchiectasie [Capitolo/Saggio]
Beghe', Bianca; A., Boner; C., Braggion; F., Luppi; Morandi, Uliano
abstract

Non disponibile

2012 - Pro-Calcitonin guided antibiotic treatment of acute exacerbations of Chrnic Obstructive Pulmonary Disease [Poster]
A., Veduri; D'Amico, Roberto; Ruggieri, Valentina; P., Vicini; A., Liverani; M., Plebani; A., Papi; Fabbri, Leonardo; Beghe', Bianca
abstract

non presente

2012 - Pulmonary comorbidities associated with chronic obstructive pulmonary disease [Articolo su rivista]
Luppi, Fabrizio; Beghe', Bianca; Roversi, Pietro
abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a relatively irreversible airflow limitation caused by chronic inflammation, in most cases tobacco-related. The impact of COPD on morbidity and mortality at the single-patient level depends upon the severity of COPD symptoms and the existence of other types of systemic and/or pulmonary disease, also known as co-morbid conditions. Materials and methods: This review examines the pulmonary diseases commonly associated with COPD, in terms of their prevalence, clinical features, pathogenic mechanisms, prognoses, and implications for management of COPD. Results: The incidence and prevalence of various pulmonary diseases are significantly increased in patients with COPD. These conditions include symptomatic bronchiectasis, combined pulmonary fibrosis and emphysema, lung cancer, sleep-related respiratory disorders, and pulmonary embolism. Some of these concomitant respiratory diseases have an independent negative impact on the prognosis of COPD patients, and their presence has important implications for treatment of these patients. Conclusions: Physicians treating patients with COPD need to be aware of these coexisting pulmonary diseases. All patients with COPD should be carefully evaluated to identify pulmonary comorbidities, since they not only influence the prognosis but also have an impact on disease management. The treatment of COPD is no longer restricted exclusively to inhaled therapy. The therapeutic approach to this disease is becoming increasingly multidimensional in view of the fact that successful management of comorbidities might positively affect the course of COPD itself. © 2011 Elsevier Srl. All rights reserved.

2012 - Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper. [Articolo su rivista]
WHO Collaborating Center for, Asthma; Rhinitis, ; Bousquet, J; Anto, Jm; Demoly, P; Schünemann, Hj; Togias, A; Akdis, M; Auffray, C; Bachert, C; Bieber, T; Bousquet, Pj; Carlsen, Kh; Casale, Tb; Cruz, Aa; Keil, T; Lodrup Carlsen, Kc; Maurer, M; Ohta, K; Papadopoulos, Ng; Roman Rodriguez, M; Samolinski, B; Agache, I; Andrianarisoa, A; Ang, Cs; Annesi Maesano, I; Ballester, F; Baena Cagnani, Ce; Basagaña, X; Bateman, Ed; Bel, Eh; Bedbrook, A; Beghe', Bianca; Beji, M; Ben Kheder, A; Benet, M; Bennoor, Ks; Bergmann, Kc; Berrissoul, F; Bindslev Jensen, C; Bleecker, Er; Bonini, S; Boner, Al; Boulet, Lp; Brightling, Ce; Brozek, Jl; Bush, A; Busse, Ww; Camargos, Pa; Canonica, Gw; Carr, W; Cesario, A; Chen, Yz; Chiriac, Am; Costa, Dj; Cox, L; Custovic, A; Dahl, R; Darsow, U; Didi, T; Dolen, Wk; Douagui, H; Dubakiene, R; El Meziane, A; Fonseca, Ja; Fokkens, Wj; Fthenou, E; Gamkrelidze, A; Garcia Aymerich, J; Gerth van Wijk, R; Gimeno Santos, E; Guerra, S; Haahtela, T; Haddad, H; Hellings, Pw; Hellquist Dahl, B; Hohmann, C; Howarth, P; Hourihane, Jo; Humbert, M; Jacquemin, B; Just, J; Kalayci, O; Kaliner, Ma; Kauffmann, F; Kerkhof, M; Khayat, G; Koffi N'Goran, B; Kogevinas, M; Koppelman, Gh; Kowalski, Ml; Kull, I; Kuna, P; Larenas, D; Lavi, I; Le, Lt; Lieberman, P; Lipworth, B; Mahboub, B; Makela, Mj; Martin, F; Martinez, Fd; Marshall, Gd; Mazon, A; Melen, E; Meltzer, Eo; Mihaltan, F; Mohammad, Y; Mohammadi, A; Momas, I; Morais Almeida, M; Mullol, J; Muraro, A; Naclerio, R; Nafti, S; Namazova Baranova, L; Nawijn, Mc; Nyembue, Td; Oddie, S; O'Hehir, Re; Okamoto, Y; Orru, Mp; Ozdemir, C; Ouedraogo, Gs; Palkonen, S; Panzner, P; Passalacqua, G; Pawankar, R; Pigearias, B; Pin, I; Pinart, M; Pison, C; Popov, Ta; Porta, D; Postma, Ds; Price, D; Rabe, Kf; Ratomaharo, J; Reitamo, S; Rezagui, D; Ring, J; Roberts, R; Roca, J; Rogala, B; Romano, A; Rosado Pinto, J; Ryan, D; Sanchez Borges, M; Scadding, Gk; Sheikh, A; Simons, Fe; Siroux, V; Schmid Grendelmeier, Pd; Smit, Ha; Sooronbaev, T; Stein, Rt; Sterk, Pj; Sunyer, J; Terreehorst, I; Toskala, E; Tremblay, Y; Valenta, R; Valeyre, D; Vandenplas, O; van Weel, C; Vassilaki, M; Varraso, R; Viegi, G; Wang, Dy; Wickman, M; Williams, D; Wöhrl, S; Wright, J; Yorgancioglu, A; Yusuf, Om; Zar, Hj; Zernotti, Me; Zidarn, M; Zhong, N; Zuberbier, T.; Anto, Jm; Demoly, P; Schünemann, Hj; Togias, A; Akdis, M; Auffray, C; Bachert, C; Bieber, T; Bousquet, Pj; Carlsen, Kh; Casale, Tb; Cruz, Aa; Keil, T; Lodrup Carlsen, Kc; Maurer, M; Ohta, K; Papadopoulos, Ng; Roman Rodriguez, M; Samolinski, B; Agache, I; Andrianarisoa, A; Ang, Cs; Annesi Maesano, I; Ballester, F; Baena Cagnani, Ce; Basagaña, X; Bateman, Ed; Bel, Eh; Bedbrook, A; B., Beghe'; Beji, M; Ben Kheder, A; Benet, M; Bennoor, Ks; Bergmann, Kc; Berrissoul, F; Bindslev Jensen, C; Bleecker, Er; Bonini, S; Boner, Al; Boulet, Lp; Brightling, Ce; Brozek, Jl; Bush, A; Busse, Ww; Camargos, Pa; Canonica, Gw; Carr, W; Cesario, A; Chen, Yz; Chiriac, Am; Costa, Dj; Cox, L; Custovic, A; Dahl, R; Darsow, U; Didi, T; Dolen, Wk; Douagui, H; Dubakiene, R; El Meziane, A; Fonseca, Ja; Fokkens, Wj; Fthenou, E.
abstract

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies

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 - Cardiovascular mechanisms of death in severe COPD exacerbation: time to think and act beyond guidelines [Articolo su rivista]
Fabbri, Leonardo; Beghe', Bianca; Agusti, Alvar
abstract

This issue of Thorax includes three important studies on acute exacerbations of chronic obstructive pulmonary disease (ECOPD). Two of them, by Chang et al. (1) and Hoiset et al. (2), show the importance of the cardiac biomarkers troponin T and NT-BNP (N-terminal pro-B-type natriuretic peptide) as strong predictors of the increased risk of death of patients hospitalized because of ECOPD (1, 2). The third, by Maclay et al. (3), provides evidence that patients with stable COPD have increased circulating platelet-monocyte aggregates—a potential specific pathogenic mechanism of atherosclerosis—and that they further increase during exacerbations, suggesting a plausible biological mechanism to explain the increased cardiovascular risk seen in ECOPD. Taken together, these studies confirm the view that ECOPD episodes requiring hospitalization must be considered very severe events in the natural course of the disease, since they are associated with such important outcomes as increased risk of mortality, reduced health status, impaired lung function, muscle weakness, and cardiopulmonary complications (4). The studies also suggest that the increased risk of death is often due to acute cardiovascular involvement, and they highlight the limitations of the current definition of ECOPD and the need to move toward a more comprehensive definition, diagnostic approach and treatment.

2011 - Infections as comorbidity of COPD [Articolo su rivista]
Luppi, F.; Beghe', B.; Roversi, P.
abstract

2011 - Interleukin-6, but not pentraxin 3, predicts adverse clinical outcomes on short-term prognosis of patients with incipient heart failure [Poster]
Boschetto, P; Bottazzi, B; Fucili, A; Potena, A; Ballerin, L; Stendardo, M; Piva, S; Verduri, Alessia; Beghe', Bianca; Mantovani, A; Fabbri, Leonardo; Ferrari, R; Ceconi, C.
abstract

non previsto

2011 - Malattie respiratorie dell'anziano [Capitolo/Saggio]
Beghe', Bianca; Roversi, Antonio
abstract

Non previsito

2011 - Roflumilast:un nuovo farmaco per il trattamento della BPCO [Articolo su rivista]
Beghe', Bianca; Verduri, Alessia; Fabbri, Leonardo
abstract

La broncopneumopatia cronica ostruttiva (BPCO) è una malattia respiratoria cronica il cui principale fattore di rischio è il fumo di sigaretta. La patologia è caratterizzata da una progressiva limitazione del flusso aereo non completamente reversibile, da sintomi respiratori quali tosse e dispnea e da frequenti riacutizzazioni cliniche che possono richiedere il ricovero ospedaliero con ulteriore compromissione dello stato di salute, declino della funzionalità respiratoria e aumento del tasso di mortalità. I farmaci attualmente disponibili per il trattamento della BPCO sono i broncodilatatori inalatori a breve (SABA) e a lunga durata d’azione (LABA). Nei pazienti con BPCO grave e molto grave e con frequenti riacutizzazioni i LABA sono somministrati in associazione con gli steroidi inalatori. L’infiammazione cronica dei polmoni gioca un ruolo cruciale nella patogenesi della BPCO. Gli inibitori della fosfodiesterasi 4 (PDE4) sono una nuova classe di farmaci ad azione antinfiammatoria che sono stati sviluppati per controllare l’infiammazione cronica correlata alla BPCO.Gli inibitori della fosfodiesterasi 4 hanno mostrato una buona efficacia e tollerabilità in studi preclinici e clinici condotti nei pazienti con BPCO

2011 - Subclinical cardiac dysfunction in moderate to severe COPD patients [Poster]
Verduri, Alessia; Bottazzi, B; Leuzzi, C; Boschetto, P; Modena, Mg; Mantovani, A; Fabbri, Leonardo; Beghe', Bianca
abstract

Non previsto

2011 - Subclinical cardiac dysfunction in moderatw to severe COPD patients [Articolo su rivista]
A., Verduri; B., Bottazzi; C., Leuzzi; P., Boschetto; Modena, Maria Grazia; A., Mantovani; Fabbri, Leonardo; Beghe', Bianca
abstract

BACKGROUND: The co-existence between chronic obstructive pulmonary disease (COPD) and heart failure has been previously described. However, the co-existence between COPD and subclinical left ventricular (LV) dysfunction, without the presence of heart failure symptoms, is less well understood. This study determined the relationship and clinical relevance of COPD and subclinical LV dysfunction in vascular surgery patients. METHODS: 1005 consecutive vascular surgery patients were included in which COPD was determined using spirometry and LV function using echocardiography. Mild COPD was defined as FEV(1)>or=80% of predicted+FEV(1)/FVC-ratio<0.70. Moderate/severe COPD was defined as FEV(1)<80% of predicted+FEV(1)/FVC-ratio<0.70. Systolic LV dysfunction was defined as LV ejection fraction <50% and diastolic LV dysfunction was diagnosed based on E/A-ratio, pulmonary vein flow and deceleration time. Multivariate regression analyses were used to evaluate the impact of COPD and LV dysfunction on all-cause mortality. The mean follow-up time was 2.2+/-1.8 years. RESULTS: Both, mild and moderate/severe COPD were associated with increased risk for subclinical LV dysfunction with odds ratio of 1.6 (95%-CI=1.1-2.3) and 1.7 (95%-CI=1.2-2.4), respectively. Mild- or moderate/severe COPD in combination with LV dysfunction was associated with increased risk for all-cause mortality (mild: hazard ratio 1.7; 95%-CI=1.1-3.6, moderate/severe: hazard ratio 2.5; 95%-CI=1.5-4.7). CONCLUSIONS: COPD was associated with increased risk for subclinical LV dysfunction. COPD+subclinical LV dysfunction was associated with increased risk for all-cause mortality compared to patients with COPD+normal LV function. Echocardiography may be useful to detect subclinical cardiovascular disease and risk-stratify COPD patients undergoing vascular surgery.

2011 - The multiple components of COPD [Capitolo/Saggio]
Fabbri, Leonardo; F., Luppi; Beghe', Bianca; K. F., Rabe
abstract

Recent research suggests that inflammation is not confined to the lungs in COPD: inflammatory cells and mediators generated in the lungs enter the bloodstream and may have systemic effects on other susceptible areas of the body. This may account for the observation that patients with COPD also present with systemic symptoms and comorbid conditions, including muscle weakness, weight loss, cardiovascular disease, osteoporosis, hypertension, depression, cognitive decline, sleep disorders, sexual dysfunction, and possibly diabetes . Considering the systemic nature of the inflammatory response to irritants, particularly cigarette smoke, there is increasing evidence that lung abnormalities may be responsible not only for respiratory symptoms, e.g., dyspnea, but also for the chronic comorbidities that develop along with COPD, particularly chronic heart failure (CHF), coronary and peripheral vascular diseases, and the metabolic syndrome. Comorbidities are highly likely to affect health outcomes in COPD, and COPD patients are more likely to die of cardiovascular complications or cancer than of respiratory failure.

2011 - le infezioni come comorbidità della BPCO [Articolo su rivista]
F., Luppi; Beghe', Bianca; P., Roversi
abstract

Le infezioni sia acute che croniche si manifestano con maggiore frequenza nei pazienti affetti con BPCO rispetto alla popolazione generale. In questo articolo vengono revisionati i meccanismi patogenetici, i quadri clinici e le strategia teraputiche

2010 - Acute exacerbations of chronic obstructive pulmonary disease: are antibiotics needed? [Articolo su rivista]
Luppi, Fabrizio; Beghe', Bianca; Richeldi, Luca
abstract

Acute exacerbations are frequent complications of chronic obstructive pulmonary disease (COPD). Individuals developing COPD exacerbations usually increase the rescue use of bronchodilators (short-acting β-2 agonist and anticholinergic drugs) and are prescribed systemic corticosteroids if they do not respond. Systemic corticosteroids significantly reduce treatment failure,shorten hospital stay,and improve symptoms and lung function. Although available evidence suggests that patients with COPD who are given antibiotics receive moderate benefit,current guidelines recommend antibiotic treatment only in patients with increased dyspnea,sputum volume,and purulence (Anthonisen criteria). The most frequent causes of COPD exacerbations are believed to be viral and/or bacterial infections. However,in most cases,the etiology of a COPD exacerbation is unknown,and clinical features are of limited help in identifying the cause and particularly in distinguishing between viral and bacterial infections. Several biomarkers (e.g.,procalcitonin) have been used to diagnose acute exacerbations of COPD due to bacterial infections,with the aim of reducing the exposure of patients to antibiotics,but their role is controversial and their use is not yet recommended by guidelines.

2010 - Asma bronchiale [Capitolo/Saggio]
Beghe', Bianca; Fabbri, Leonardo; A., Papi
abstract

L’asma (parola greca che significa "senza respiro" o "respiro a bocca aperta") bronchiale è una malattia infiammatoria cronica delle vie aeree che si manifesta clinicamente con 1) episodi ricorrenti di respiro sibilante e/o senso di costrizione toracica, dispnea, tosse non produttiva o accompagnata da espettorato bianco e tenace, 2) ostruzione bronchiale reversibile, e 3) iperreattività bronchiale. Il carattere accessuale e reversibile delle manifestazioni clinica e funzionali rappresenta la caratteristica peculiare della malattia. L’infiammazione bronchiale cronica delle vie aeree che sottende le manifestazioni clinico-funzionali dell’asma è costituita da una specifica infiltrazione bronchiale di cellule infiammatorie, in particolare granulociti eosinofili e mastociti, rilascio di mediatori infiammatori, e rimodellamento strutturale delle vie aeree caratterizzato in particolare da ipertrofia/iperplasia della muscolatura liscia e fibrosi sub-epiteliale. .

2010 - Asthma [Capitolo/Saggio]
Beghe', Bianca; Fabbri, Leonardo
abstract

Asthma is a chronic inflammatory disease ofthe airways, characterised clinically byrecurrent respiratory symptoms: dyspnoea,wheezing, chest tightness and/or cough,almost always associated with reversibleairflow limitation.The diagnosis of asthma is based on clinicalhistory and lung function tests, particularlypeak expiratory flow (PEF) and spirometry,with assessment of variable and/or reversibleairflow limitation. Allergy tests are alsousually performed during the first assessmentof a patient with suspected asthma to identifypossible triggers of asthma and to guide theiravoidance.

2010 - Development and implementation of guidelines in allergic rhinitis – an ARIA-GA2LEN paper. [Articolo su rivista]
Bousquet, J; Schünemann, Hj; Zuberbier, T; Bachert, C; Baena Cagnani, Ce; Bousquet, Pj; Brozek, J; Canonica, Gw; Casale, Tb; Demoly, P; Gerth van Wijk, R; Ohta, K; Bateman, Ed; Calderon, M; Cruz, Aa; Dolen, Wk; Haughney, J; Lockey, Rf; Lötvall, J; O'Byrne, P; Spranger, O; Togias, A; Bonini, S; Boulet, Lp; Camargos, P; Carlsen, Kh; Chavannes, Nh; Delgado, L; Durham, Sr; Fokkens, Wj; Fonseca, J; Haahtela, T; Kalayci, O; Kowalski, Ml; Larenas Linnemann, D; Li, J; Mohammad, Y; Mullol, J; Naclerio, R; O'Hehir, Re; Papadopoulos, N; Passalacqua, G; Rabe, Kf; Pawankar, R; Ryan, D; Samolinski, B; Simons, Fe; Valovirta, E; Yorgancioglu, A; Yusuf, Om; Agache, I; Aït Khaled, N; Annesi Maesano, I; Beghe', Bianca; Ben Kheder, A; Blaiss, Ms; Boakye, Da; Bouchard, J; Burney, Pg; Busse, Ww; Chan Yeung, M; Chen, Y; Chuchalin, Ag; Costa, Dj; Custovic, A; Dahl, R; Denburg, J; Douagui, H; Emuzyte, R; Grouse, L; Humbert, M; Jackson, C; Johnston, Sl; Kaliner, Ma; Keith, Pk; Kim, Yy; Klossek, Jm; Kuna, P; Le, Lt; Lemiere, C; Lipworth, B; Mahboub, B; Malo, Jl; Marshall, Gd; Mavale Manuel, S; Meltzer, Eo; Morais Almeida, M; Motala, C; Naspitz, C; Nekam, K; Niggemann, B; Nizankowska Mogilnicka, E; Okamoto, Y; Orru, Mp; Ouedraogo, S; Palkonen, S; Popov, Ta; Price, D; Rosado Pinto, J; Scadding, Gk; Sooronbaev, Tm; Stoloff, Sw; Toskala, E; van Cauwenberge, P; Vandenplas, O; van Weel, C; Viegi, G; Virchow, Jc; Wang, Dy; Wickman, M; Williams, D; Yawn, Bp; Zar, Hj; Zernotti, M; Zhong, N; WHO Collaborating Center of, Asthma; Rhinitis,
abstract

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

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 - Malattie infiammatorie delle vie aeree superiori [Capitolo/Saggio]
C., Bucca; E., Rovatti; Beghe', Bianca
abstract

Le vie aeree superiori si estendono dalle narici alla laringe e sono in continuità con le vie aeree inferiori, che si estendono dalla trachea agli alveoli. I due tratti respiratori, superiore e inferiore, hanno molte caratteristiche in comune ma anche caratteristiche distintive. La rinite è rinorrea anteriore e/o posteriore, starnuto, ostruzione e prurito nasali, presenti per almeno 1 ora al giorno per almeno 2 giorni consecutivi. Numerose condizioni, allergiche e non allergiche, possono causare tali sintomi.

2010 - Microsatellite alterations suggestive of organ-specific asthma and atopy in exhaled breath condensate [Articolo su rivista]
G. E., Carpagnano; A., Spanevello; Beghe', Bianca; R., Prato; M. P., Barbaro
abstract

Exhaled microsatellite alterations at chromosomes 6p and14q are suggestive of organ-specific asthma and atopy.

2010 - Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease [Articolo su rivista]
Beghe', Bianca; I. P., Hall; M. F., Moffatt; A., Wardlaw; M. J., Connolly; Fabbri, Leonardo; C., Ruse; I., Sayers
abstract

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults.Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6- were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV(1), FEV(1)/FVC).In asthmatics, three IL13 SNPs - rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) - were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925(-1111) were associated with better FEV(1) and FEV(1)/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV(1).These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.

2010 - Roflumilast [Articolo su rivista]
Fabbri, Leonardo; Beghe', Bianca; Yasothan, U; Kirkpatrick, P.
abstract

In July 2010, roflumilast (Daxas; Nycomed)was granted marketing authorizationby the European Commission for themaintenance treatment of severe chronicobstructive pulmonary disease, as anadd-on to bronchodilator treatment

2009 - Clinical assessment of asthma and COPD. [Capitolo/Saggio]
F., Luppi F; Beghe', Bianca; L., Corbetta; L. M., Fabbri
abstract

Asthma and COPD are 2 different chronic inflammatory respiratory disorders that may share one common functional abnormality, i.e. poorly reversible airflow limitation . According to definitions, airflow limitation in asthma is reversible or at least partly reversible either spontaneously or with treatment , whereas in COPD airflow limitation is usually poorly reversible or not reversible at all.In the pathogenesis of both asthma and COPD, individual genetic susceptibility and environmental exposures are relevant for disease expression. Cigarette smoking is the major cause of COPD; the causes of asthma remain largely uncertain, even if atopy and allergen exposure have certainly a major role asthma is in fact a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described; in particular asthma starting in adulthood, noneosinophilic asthma, and asthma in obese subjects constitute an important part of the adult asthma population, and are still poorly characterize. The differential diagnosis between asthma and COPD is quite simple when considering the typical clinical and functional features of these 2 diseases. In this context, it is easy to recognise asthma in a young, atopic, non smoking subject with recurrent dyspnoea, wheezing or chest tightness, and variable reversible airflow limitation. It is also easy to diagnose COPD in a subject older than 40, smoker, presenting with dyspnoea, chronic cough, sputum and fixed airflow limitation and no history of asthma or allergic diseases. The difficulty comes when trying to make a diagnosis of asthma and/or COPD in a middle age or elderly patient, smoker, maybe atopic and/or with a history of asthma, complaining chronic dyspnoea but not wheezing, nor chronic cough and sputum, and presenting with poorly reversible airflow limitation. The difficulty comes also when trying to make a confirm diagnosis of asthma or establish a diagnosis of COPD in a middle age or elderly patient, with a clear history of atopy and asthma, bronchodilator reversibility, recurrent wheezing, but who also smokes and have chronic cough and sputum, and dyspnea, that are nor suppressed by inhaled steorids. In these “borderline” patients, differential diagnosis might become important from a clinical and therapeutic point of view. In fact, inhaled glucocorticosteroids are the first choice regular medication in asthma but not in COPD, whereas regular bronchodilators are the first choice regular medication in COPD but not in asthma, and thus the differential diagnosis between asthma and COPD is important to decide whether or not prescribing regular treatment with steroids or bronchodilators in patients with overlapping features.

2009 - Diagnosis of asthma and copd [Capitolo/Saggio]
Luppi, F.; Beghe', B.; Corbetta, L.; Fabbri, L. M.
abstract

The differential diagnosis between asthma and COPD is quite simple when the typical clinical and functional features of either disease are present. The difficulty comes when trying to make a diagnosis of asthma or COPD in a middle-aged or elderly patient, a smoker, who may be atopic or have a history of asthma, who complains of chronic dyspnea but not wheezing, chronic cough, or sputum, and who presents with poorly reversible airflow limitation. It is also difficult to make a diagnosis of asthma or COPD in a middle-aged or elderly patient who has a clear history of atopy and asthma, bronchodilator reversibility, and recurrent wheezing, but who also smokes and has chronic cough and sputum and dyspnea that are not suppressed by inhaled steroids. The diagnosis of asthma or COPD is based on clinical history and lung function tests, particularly peak expiratory flow (PEF) and spirometry, with assessment of spontaneous or postbronchodilator reversibility of airflow limitation. Allergy tests are also usually performed for the diagnosis of asthma, but not of COPD patients, to identify allergens responsible for asthma exacerbations and to consider the opportunity to treat the patient with immunotherapy. While the diagnosis and assessment of severity of asthma and COPD can be fully established on the basis of clinical history and lung function tests, additional tests might be helpful to better characterize individual patients. © 2009 Elsevier Ltd All rights reserved.

2008 - Complex chronic co-morbidities of COPD [Articolo su rivista]
Fabbri, Leonardo; Luppi, Fabrizio; Beghe', Bianca; K. F., Rabe
abstract

Chronic obstructive pulmonary disease (COPD) is defined by fixed airflow limitation associated with an abnormal pulmonary and systemic inflammatory response of the lungs to cigarette smoke. The systemic inflammation induced by smoking may also cause chronic heart failure, metabolic syndrome and other chronic diseases, which may contribute to the clinical manifestations and natural history of COPD. Thus COPD can no longer be considered a disease only of the lungs, as it is often associated with a wide variety of systemic consequences. A better understanding of the origin and consequences of systemic inflammation, and of potential therapies, will most likely lead to better care of patients with COPD. Medical textbooks and clinical guidelines still largely ignore the fact that COPD seldom occurs in isolation. As the diagnosis and assessment of severity of COPD may be greatly affected by the presence of comorbid conditions, the current authors believe that lung function measurement, noninvasive assessment of cardiovascular and metabolic functions, and circulating inflammatory markers (e.g. C-reactive protein) might help to better characterise these patients. Similarly, preventive and therapeutic interventions should address the patient in their complexity.

2008 - Genetics of Asthma: What's New? [Capitolo/Saggio]
Sayers, I.; Beghe, Bianca; Holloway, J.; Holgate, S. T.
abstract

Asthma is a complex disorder involving a combination of genetic and environmental interactions that lead to airway inflammation characterised by TH2 T cell polarisation and airway wall remodelling accompanied by extensive epithelial dysfunction. Allergen exposure is the single most powerful environmental risk factor for asthma, although there are forms that accompany occupational exposures and forms where no allergen has been identified. Recently there has been an increase in morbidity associated with asthma and there is strong evidence that asthma and allergic disorders are increasing in prevalence and severity (see Chapter 1 in this series).

2008 - La broncopneumopatia cronica ostruttiva [Capitolo/Saggio]
R., Zuin; Beghe', Bianca; G., Turato; M., Saetta
abstract

La broncopneumopatia cronica ostruttiva (BPCO) è una condizione clinica caratterizzata da una limitazione al flusso aereo che non è completamente reversibile. La limitazione al flusso aereo è di solito progressiva ed associata ad una anomala risposta infiammatoria dei polmoni all’inalazione di agenti, particelle o gas, nocivi. I principali sintomi della BPCO sono la tosse, l’espettorato e la dispnea 1Molte delle definizioni precedenti di BPCO comprendevano i termini “enfisema” e “bronchite cronica”, non più enfatizzati come singole entità nella definizione attuale. L’enfisema, o distruzione della superficie di scambio dei gas, è un termine anatomopatologico che descrive solo una delle numerose alterazioni strutturali in grado di causare la limitazione al flusso aereo caratteristica della BPCO. La bronchite cronica, o presenza di tosse ed espettorato cronici, è un termine clinico che non descrive l’aspetto funzionale della malattia, cioè la limitazione al flusso aereo.E’ importante sottolineare che, mentre nella maggior parte dei pazienti, i sintomi di bronchite cronica precedono lo sviluppo della limitazione al flusso aereo, in altri pazienti ci può essere un’importante limitazione al flusso aereo in assenza di sintomi di bronchite cronica. Infine, ci sono alcuni pazienti con tosse ed espettorato cronici che non sviluppano mai limitazione al flusso aereo. Queste osservazioni indicano che anche se la BPCO è in generale caratterizzata da peggioramento progressivo della limitazione al flusso aereo, in realtà la storia clinica della malattia può variare da individuo a individuo, e di questo bisogna tener conto nell’inquadramento clinico e terapeutico del singolo paziente.In questo capitolo la BPCO verrà trattata in esteso, dalla patogenesi alla terapia

2008 - La genetica dell’asma bronchiale. [Capitolo/Saggio]
R., Zuin; M., Saetta; S., Lauro; Beghe', Bianca
abstract

L’asma bronchiale è una malattia infiammatoria cronica delle vie aeree caratterizzata da ricorrenti episodi di ostruzione reversibile del flusso aereo responsabili delle crisi di respiro sibilante, senso di costrizione toracica, dispnea e tosse stizzosa1. L’atopia, definita come un aumento della sintesi di immunoglobuline E (IgE) in risposta all’esposizione a comuni allergeni, è uno dei il fattore di rischio più importanti per la comparsa di asma 2. Da un punto di vista genetico, l’asma bronchiale è una malattia genetica complessa dovuta all’interazione tra fattori genetici, che conferiscono soprattutto la predisposizione alla comparsa dell’asma, e fattori ambientali, quali allergeni, inquinanti atmosferici ed infezioni che agiscono soprattutto come fattori scatenanti la malattia.In questo capitolo dopo una breve introduzione allo studio delle malattie genetiche complesse, passeremo in rassegna gli studi ed i progressi compiuti nell’identificare i geni potenzialmente coinvolti nella patogenesi dell’asma.

2008 - Pharmacological prevention of COPD exacerbations [Capitolo/Saggio]
Beghe', Bianca; F., Luppi; Fabbri, Leonardo
abstract

Exacerbations of COPD are characterized by changes in the patient’s baseline dyspnoea, cough, and/or sputum that are beyond normal day-to-day variations, that are acute in onset, and that may warrant a change in regular medication. The frequency and severity of exacerbations increase with disease severity and are associated with poorer quality of life and health outcomes, with a greater burden on health care, accelerated decline of lung function, and increased risk of death. For all these reasons, exacerbations are a major target of prevention and treatment in patients with COPD.While exacerbations are increasingly used as primary outcome or secondary pre-specified outcome in clinical trials in COPD, major limitations of the studies on COPD exacerbations are that the definition is based on symptoms and not on objective measurements. Furthermore, the definition varies between studies, and often comorbidities are not adequately taken into account. Worsening of daily respiratory symptoms, particularly dyspnoea, could be associated with respiratory events, such as pneumonia, or non respiratory events, such as heart failure, thromboembolisms, and renal failure, among others. Long-acting bronchodilators alone or in combination with inhaled glucocorticosteroids are the most effective treatment for reducing the number and severity of COPD exacerbations—even though caution is required in interpreting the results of some trials. Suissa and coworkers, in their recent papers on methodological issues, suggest that the results of major randomized controlled clinical trials that evaluate the effect of treatment on COPD exacerbations might be biased by the facts that many patients enrolled in the studies are already receiving inhaled therapy before randomization, and that the results could be influenced by withdrawal from the ongoing effective therapy. Another bias might be that patients included in the trials are often not followed after discontinuation of treatment; considering the different rates of withdrawal between treatments and the different causes of withdrawal, this may severely affect the interpretation of the data. Statistical methods are also critical. A statistical approach that does not weight for the length of the follow-up (unweighted approach), and for the within- and between-subject variability of exacerbations, may lead to false-positive results. In particular, this bias applies to all but two trials examining the effect of inhaled glucocorticosteroids on exacerbations, causing the authors of those studies to conclude that the positive effect of inhaled glucocorticosteroids on exacerbations is not supported by solid evidence. With these limitations, however, randomised controlled trials are and will remain the fundamental tools for evaluating the benefit of COPD treatment, and the data collected so far, albeit with the potential biases, are the only evidence available to support treatment recommendations.In this chapter we review the various classes of medications commonly used in treating COPD. We focus on the most effective medications for preventing exacerbations, such as inhaled long-acting bronchodilators alone or in combination with inhaled glucocorticosteroids. Also, considering their importance in the management of COPD, we briefly discuss the effects of smoking cessation and vaccinations on COPD exacerbations. We do not discuss the effects of treatment of exacerbations on subsequent exacerbations—obviously an important clinical aspect. In fact, short-term therapy with oral glucocorticosteroids after hospitalization for a COPD exacerbation reduces the likelihood of readmission for another exacerbation.

2008 - Treatment of chronic obstructive pulmonary disease and its comorbidities [Relazione in Atti di Convegno]
Luppi, Fabrizio; Franco, F; Beghe', Bianca; Fabbri, Leonardo
abstract

While chronic obstructive pulmonary disease (COPD) is still characterized and diagnosed by lung function measurements, there is increasing evidence that the chronic diseases that frequently develop with COPD in response to the common risk factors (smoking, aging, obesity) may contribute significantly to its clinical manifestations and severity. Considering that pharmacologic and nonpharmacologic treatments of COPD, such as pulmonary rehabilitation, are primarily symptomatic, it is reasonable to hope that a more comprehensive management of COPD that takes into account its comorbidities may improve the response to treatment and reduce mortality in patients with COPD. Thus, as comorbidities are often underdiagnosed and undertreated, it is important to search for their coexistence in COPD and in all chronic diseases, possibly by adopting recommendations for diagnosis of single diseases. This means that while careful cardiovascular, metabolic, and endocrinologic examinations should be increasingly used in assessing patients with COPD, lung function measurements may become useful in patients with chronic cardiovalscular, metabolic, and endocrinologic diseases. The increasing evidence that active treatment of comorbidities (by, e.g., statins and beta-blockers) may reduce morbidity and mortality in patients with COPD suggests the urgent need for randomized clinical trials that hopefully will provide the evidence for more comprehensive clinical guidelines for these patients.

2007 - Update in chronic obstructive pulmonary disease 2006 [Articolo su rivista]
K. F., Rabe; Beghe', Bianca; F., Luppi; Fabbri, Leonardo
abstract

Chronic obstructive pulmonary disease (COPD) is increasinglyrecognized as a major health care problem and the numberof publications in the scientific literature is a reflection of thisincreased awareness. This update cannot do justice to allnewly available information, but it does represent a selection ofarticles that were considered to be of sufficient general interestto warrant further discussion.

2006 - The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma [Articolo su rivista]
L., Hao; I., Sayers; J. A., Cakebread; S. J., Barton; Beghe', Bianca; S. T., Holgate; A. P., Sampson; J. W., Holloway
abstract

BACKGROUND: The cysteinyl-leukotriene receptor type 1 (CysLT1) mediates the bronchoconstrictor and pro-inflammatory actions of cysteinyl-leukotrienes (LTC4, LTD4, LTE4) in asthma and is the molecular target of the lukast class of oral anti-leukotriene drugs. We screened the CYSLTR1 gene on chromosome Xq13-21 for coding region polymorphisms, and investigated their associations with allergy and asthma. METHODS: Solid-phase chemical cleavage was used to screen polymorphisms in the coding region of CYSLTR1. A TaqMan allelic discrimination assay was used to genotype a 927T/C SNP and oligonucleotide ligation assays were used to genotype the previously reported 617T/C and 898G/A SNPs of CYSLTR1 in 341 asthmatic families from the UK. Associations with asthma diagnosis, atopic status, serum-specific IgE and severity of allergy and asthma were examined. RESULTS: Family-based association tests showed that the 927 T allele was associated with atopy severity, especially in female subjects, but not with asthma diagnosis or severity, atopic status, bronchial hyper-responsiveness to methacholine or forced expiratory volume in 1 s. CONCLUSION: Mutation screening identified only one polymorphism, 927T/C, in the coding region of the CysLT1 receptor. This polymorphsim is predictive of atopy severity, but not associated with asthma.

2006 - Transforming growth factor-β type II receptor in pulmonary arteries of patients with very severe COPD [Articolo su rivista]
Beghe', Bianca; E., Bazzan; S., Baraldo; F., Calabrese; F., Rea; M., Loy; P., Maestrelli; R., Zuin; Fabbri, Leonardo; M., Saetta
abstract

A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-beta is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-beta pathway might be involved in the development of pulmonary hypertension associated with COPD. Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17 +/- 2% of the predicted value) and from seven donors were examined. The expression of TGF-beta1 and TGF-beta type II receptor (TGF-betaRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically. In severe COPD patients, increased expression of TGF-betaRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening. In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-beta type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

2006 - Update in Chronic Obstructive Pulmonary Disease 2005 [Articolo su rivista]
Fabbri, Leonardo; F., Luppi; Beghe', Bianca; Kf, Rabe
abstract

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that has a large impact on quality of life for patients and their families and kills millions of people worldwide. Even though there have been significant advances in the understanding and management of COPD, suggesting that the disease may be largely preventable, it remains only marginally treatable. This is probably because COPD is due to a slowly progressive destructive process of the lung that is poorly reversible when manifested clinically, and because it has systemic effects and frequent comorbidities that should be managed more comprehensively.The interest in COPD by the medical and scientific community has increased dramatically in the last decade, as reflected by the number of publications in both pulmonary and general medical journals. This review aims to summarize and highlight progress in the understanding of COPD in 2005. Although we found most of the articles interesting, we had to be selective, and we take full responsibility for the choices we have made.

2005 - Decreased expression of TGF-beta type II receptor in bronchial glands of smokers with COPD [Articolo su rivista]
S., Baraldo; E., Bazzan; G., Turato; F., Calabrese; Beghe', Bianca; A., Papi; P., Maestrelli; Fabbri, Leonardo; R., Zuin; M., Saetta
abstract

BACKGROUND: The role of transforming growth factor-beta1 (TGF-beta1) in chronic obstructive pulmonary disease is still controversial, but it has been proposed that it may protect from mucus hypersecretion since it is able to downregulate mucin production. A study was undertaken to investigate the expression of TGF-beta1 and its type II receptor (TGF-beta RII) in the bronchial glands of smokers with COPD. METHODS: The expression of TGF-beta and TGF-beta RII were examined immunohistochemically in the bronchial glands of 24 smokers undergoing lung resection for solitary peripheral nodules: 12 with airflow limitation (smokers with COPD) and 12 with normal lung function. RESULTS: The expression of TGF-beta1 in bronchial glands was similar in the two groups of subjects while that of TGF-beta RII was lower in smokers with COPD than in smokers with normal lung function (p=0.004). TGF-beta RII expression was inversely correlated with the values of Reid's index, a measure of gland size (p=0.02, r=-0.50). CONCLUSIONS: In the bronchial glands of smokers with COPD there is decreased expression of TGF-beta RII which is associated with bronchial gland enlargement. These findings support the view that the absence of TGF-beta signalling may induce structural changes in the bronchial glands which, in turn, may promote mucus hypersecretion.

2005 - Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema [Articolo su rivista]
Fiorella, Calabrese; Cinzia, Giacometti; Beghe', Bianca; Federico, Rea; Monica, Loy; Renzo, Zuin; Giuseppe, Marulli; Simonetta, Baraldo; Marina, Saetta; Marialuisa, Valente
abstract

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.

2005 - Role for CXCR6 and its Ligand CXCL16 in the Pathogenesis of T-cell Alveolitis in Sarcoidosis [Articolo su rivista]
C., Agostini; A., Cabrelle; F., Calabrese; M., Bortoli; E., Scquizzato; S., Carraro; M., Miorin; Beghe', Bianca; L., Trentin; R., Zambello; M., Facco; G., Semenzato
abstract

RATIONALE: Receptor expression dictates the spectrum of chemokine actions on immunocompetent cells. We have previously shown that the chemokine receptor CXCR3 is highly expressed by T-helper type 1 (Th1) cells infiltrating the lungs of patients with sarcoidosis. OBJECTIVES: The evaluation of the role of Bonzo/CXCR6 and its ligand CXCL16 in the pathogenesis of sarcoidosis. METHODS: Immunocompetent cells infiltrating sarcoid lung have been evaluated by flow cytometry, confocal microscopy, immunohistochemical and molecular analysis, and functional assays. MAIN RESULTS: Th1 cells isolated from the bronchoalveolar lavage of patients with sarcoidosis and T-cell alveolitis coexpressed CXCR3 and CXCR6. Immunohistochemical analysis of lung specimens has shown that CXCR6+ T cells infiltrated lung interstitium surrounding the central core of the granuloma. The CXCR6 ligand CXCL16 was abundantly expressed by macrophages infiltrating sarcoid tissue and/or forming the granuloma core. From a functional point of view, sarcoid Th1 cells were able to respond to CXCL10 and CXCL16 in migratory assay. In vitro kinetic studies demonstrated that, although CXCR3 was rapidly induced by interleukin (IL)-15 and IL-18, CXCR6 induction was slow (8 d) and mainly regulated by IL-15. CONCLUSIONS: T cells coexpressing CXCR3 and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease.

2004 - Corticosteroid and immunomodulatory agents in idiopathic pulmonary fibrosis [Articolo su rivista]
F., Luppi; Cerri, Stefania; Beghe', Bianca; Fabbri, Leonardo; Richeldi, Luca
abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease leading to death within a few years of diagnosis despite medical therapy. On the basis of methodologies of the Cochrane collaboration, this overview discusses the evidence for IPF therapy. Good-quality studies on oral corticosteroids, the most common medical therapy in use for IPF, are lacking. A few small studies have been carried out on the efficacy of many non-steroid immunosuppressive agents, and the results have been generally disappointing. The most extensively studied medical therapy, gamma interferon, showed a significant effect in a small randomized study, but its efficacy was not confirmed in a larger randomized-controlled trial. The long-awaited good news for patients affected by this deadly disease, and for their physicians, could come in the near future from large randomized-controlled trials with gamma interferon or other immunomodulatory agents.

2004 - Lack of association of HLA class I genes and TNF alpha-308 polymorphism in toluene diisocyanate-induced asthma. [Articolo su rivista]
Beghe', Bianca; M., Padoan; C. T., Moss; S. J., Barton; J. W., Holloway; S. T., Holgate; W. M., Howell; C. E., Mapp
abstract

BACKGROUND: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational asthma and it affects 5-15\% of the exposed population suggesting an underlying genetic susceptibility. METHODS: To investigate the role of genetic factors in the development of TDI-induced asthma, we analyzed the distribution of human leukocyte antigen (HLA) class I genes and of tumor necrosis factor (TNF)-alpha A-308G polymorphism in 142 patients with TDI-induced asthma and in 50 asymptomatic exposed subjects. RESULTS: Neither the distribution of HLA class I antigens nor the distribution of TNF-alpha A-308G polymorphism was different between patients with TDI-induced asthma and asymptomatic exposed subjects. CONCLUSIONS: These results suggest that HLA class I antigens and TNF-alpha A-308G are not associated with susceptibility or resistance to the development of TDI-induced asthma.

2004 - Neutrophilic infiltration within the airway smooth muscle in patients with COPD [Articolo su rivista]
S., Baraldo; G., Turato; C., Badin; E., Bazzan; Beghe', Bianca; R., Zuin; F., Calabrese; G., Casoni; P., Maestrelli; A., Papi; Fabbri, Leonardo; M., Saetta
abstract

BACKGROUND: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. METHODS: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. RESULTS: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). CONCLUSIONS: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation.

2003 - Airway inflammation in childhood asthma [Articolo su rivista]
A., Barbato; G., Turato; S., Baraldo; E., Bazzan; F., Calabrese; M., Tura; R., Zuin; Beghe', Bianca; P., Maestrelli; L., Fabbri; M., Saetta
abstract

Airway pathology has been extensively investigated in adulthood asthma, whereas only few studies examined bronchial biopsies in childhood asthma. To evaluate the airway pathology in children with asthma, we analyzed bronchial biopsies obtained from 23 children undergoing bronchoscopy for clinical indications other than asthma. Nine had mild/moderate asthma. Six had atopy without asthma, and eight had no atopy or asthma. We measured basement membrane thickness and quantified the number of eosinophils, mast cells, neutrophils, macrophages, T lymphocytes, and positive cells for transforming growth factor-beta1 (TGF-beta1) and its receptors I and II (TGFbeta-RI and TGFbeta-RII) in subepithelium. Children with asthma had an increase in basement membrane thickness and in the number of eosinophils compared with control subjects, but not compared with children with atopy. They also had a decreased expression of TGFbeta-RII compared with both those with atopy and control subjects. In children with asthma, the number of eosinophils correlated negatively with TGFbeta-RII and positively with symptom duration. In conclusion, airway eosinophilia and basement membrane thickening, which are the pathologic features that are characteristic of adulthood asthma, are already present in children with mild asthma, and even in children with atopy without asthma. Moreover, in children with asthma but not in children with atopy without asthma, there is a downregulation of TGFbeta-RII

2003 - Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma. [Articolo su rivista]
I., Sayers; S., Barton; S., Rorke; Beghe', Bianca; B., Hayward; P., Van Eerdewegh; T., Keith; J. B., Clough; S., Ye; J. W., Holloway; A. P., Sampson; S. T., Holgate
abstract

BACKGROUND: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 (A/C) polymorphism has previously been reported. The role of these polymorphisms in the genetic susceptibility to asthma was examined. METHODS: To test for genetic association with asthma phenotypes, 341 white families (two asthmatic siblings) and 184 non-asthmatic control subjects were genotyped. Genetic association was assessed using case control and transmission disequilibrium test (TDT) analyses. LTC4S promoter luciferase constructs and transiently transfected human HeLa and KU812F cells were generated to determine the functional role of these polymorphisms on basal transcription. RESULTS: No associations were observed in case control analyses (-1072 A, q=0.09; -444 C, q=0.29); the TDT identified a borderline association between the -444 C allele and bronchial responsiveness to methacholine (p=0.065). Asthmatic children with the -444 C allele had a lower mean basal forced expiratory volume in 1 second (97.4 v 92.7\% predicted, p=0.005). LTC4S promoter luciferase analyses provided no evidence for a functional role of either polymorphism in determining basal transcription. CONCLUSION: This study does not support a role for these polymorphisms in genetic susceptibility to asthma but provides evidence to suggest a role in determining lung function parameters.

2003 - Alveolar and bronchiolar inflammation in COPD [Capitolo/Saggio]
S. B. a. r. a. l. d. o., . G. Turato; Beghe', Bianca; R., ZUIN R; M., Saetta
abstract

Chronic obstructive pulmonary disease is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli, most commonly cigarette smoke. Although cigarette smoking elicits airway inflammation in all of those who smoke, persistent inflammation and clinically significant COPD occurs in only a minority of smokers.

2003 - Expression of TGF β -1 and TGF β -1RII in pulmonary arteries of patients with severe COPD. [Articolo su rivista]
Beghe', Bianca; Bazzan, E; Calabrese, F; Zuin, R; Turato, G; Baraldo, S; Regorda, C; Schiraldi, C; Rea, F; Maestrelli, P; B., Beghe'
abstract

2003 - Increased proportion of CD8(+) T-lymphocytes in the paratracheal lymph nodes of smokers with mild COPD [Articolo su rivista]
M., Saetta; S., Baraldo; G., Turato; Beghe', Bianca; Gl, Casoni; Cm, Bellettato; F., Rea; R., Zuin; Fabbri, Leonardo; A., Papi
abstract

Previous studies have shown an increased number of inflammatory cells and, in particular, of CD8+ T lymphocytes, in central airways, peripheral airways, lung parenchyma and pulmonary arteries of smokers with COPD. In this study we investigated whether this inflammatory process is restricted to the lung tissue or whether a similar process is also present in the lymph nodes of these subjects. We examined paratracheal lymph nodes obtained from 6 smokers with COPD (FEV1/VC < 88% predicted and FEV1/FVC < 70% both before and after 200 microg of inhaled salbutamol) and 6 smokers without COPD (FEV1/VC > 88% predicted and FEV1/FVC > 70%) undergoing lung resection for localised pulmonary lesions. By immunohistochemistry we quantified CD4+ and CD8+ T-lymphocytes in the lymph nodes. Smokers with COPD had a decreased ratio CD4/CD8 compared to smokers without COPD. When all subjects were considered together, the ratio CD4/CD8 showed a positive correlation with the values of FEV1/VC and a negative correlation with cigarette consumption. In conclusion, smokers with COPD have an increased proportion of CD8+ cells in the lymph nodes, indicating that a T-lymphocyte pattern similar to that present in the lung tissue is also present in the lymph nodes of these subjects. This finding suggests that, in COPD, the polarisation of the immune response may occur in the regional lymph nodes, possibly as a consequence of the presentation of an endogenous antigen that remains unknown.

2003 - Polymorphisms in the interleukin-4 and interleukin-4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population [Articolo su rivista]
Beghe', Bianca; S., Barton; S., Rorke; Q., Peng; I., Sayers; T., Gaunt; T. P., Keith; J. B., Clough; S. T., Holgate; J. W., Holloway
abstract

BACKGROUND : IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype. OBJECTIVE : To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma. METHODS : Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England. RESULTS : Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006). CONCLUSION : Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.

2003 - Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. [Articolo su rivista]
I., Sayers; S., Barton; S., Rorke; J., Sawyer; Q., Peng; Beghe', Bianca; S., Ye; T., Keith; J. B., Clough; J. W., Holloway; A. P., Sampson; S. T., Holgate
abstract

BACKGROUND: 5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma. OBJECTIVE: We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility. METHODS: To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184). Genetic association was determined by case-control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP-promoter-luciferase constructs and transiently transfected human HeLa cells. RESULTS: A novel G/A substitution at -336 bp and a poly(A) repeat (n=19 or 23) at position -169 to -146 bp were identified in the ALOX5AP promoter. Genotyping found the -336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma-related phenotypes in case-control or TDT analyses. ALOX5AP-promoter-luciferase analyses did not support a functional role of the -336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild-type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma-related phenotypes. CONCLUSION: Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.

2003 - The Genetics of Asthma. [Capitolo/Saggio]
J. W., Holloway; H., Jongepier H; Beghe', Bianca; G. H., Koppelman; S. T., Holgate; D. S., Postma
abstract

Asthma is a complex disease due to an interction between genetic and enviromental factors. In this chapeter we will discuss new advances in the gentic of this disease

2003 - [Pathology of chronic obstructive pulmonary disease] [Articolo su rivista]
G., Turato; R., Zuin; S., Baraldo; C., Badin; Beghe', Bianca; M., Saetta
abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung characterized by poorly reversible airflow limitation. It is not a unique disease entity but rather a complex of conditions which include emphysema, chronic bronchitis and, sometimes, asthma. Moreover, COPD is a progressive disease often associated with exacerbations. Cigarette smoking, which is the most important risk factor for the development of COPD, induces pathological changes involving lung parenchyma, peripheral airways and central airways. Since lung parenchyma and peripheral airways are the sites responsible for airflow limitation and central airways are the main site of mucus hypersecretion, pathological changes in these compartments may be relevant in the development of COPD.

2002 - Airway inflammation in severe chronic obstructive pulmonary disease - Relationship with lung function and radiologic emphysema [Articolo su rivista]
G., Turato; R., Zuin; M., Miniati; S., Baraldo; F., Rea; Beghe', Bianca; S., Monti; B., Formichi; P., Boschetto; S., Harari; A., Papi; P., Maestrelli; Fabbri, Leonardo; M., Saetta
abstract

The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV1] = 29 +/- 3% predicted, n = 9) or mild/no airflow limitation (FEV1 = 86 +/- 5% predicted, n = 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV1 and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8(+) and CD4(+) T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.

2002 - Basi strutturali della BPCO. [Articolo su rivista]
G., Turato; R., Zuin; S., Baraldo S; Beghe', Bianca; E., Bazzan; M., Saetta
abstract

La BroncoPneumopatia Cronica Ostruttiva o BPCO è una malattia a carico dell’apparato respiratorio e comprende la bronchite cronica e l’enfisema polmonare. La bronchite cronica, definita come la presenza di tosse ed espettorato per almeno tre mesi all’anno per due anni consecutivi, coinvolge i bronchi che si restringono perché infiammati e pieni di muco. L’enfisema polmonare è una distruzione irreversibile degli alveoli polmonari che impedisce gli scambi gassosi.Entrambe le malattie compromettono la funzionalità respiratoria, pertanto la diagnosi di BPCO deve essere fatta con prove di funzionalità respiratoria, in particolare con la spirometria.La BPCO è una malattia lentamente progressiva caratterizzata da periodi di stabilità clinica e da periodi di peggioramento dei sintomi che vengono indicati come riacutizzazioni della malattia.La BPCO è patologia molto frequente, con un notevole impatto sociale in termini di morbilità e mortalità. Nei paesi industrializzati rappresenta oggi la quarta causa di morte e secondo le stime dell’Organizzazione Mondiale della Sanità la sua incidenza è in continuo aumento. E’ una malattia che interessa entrambi i sessi con una leggera prevalenza nel sesso maschile. Tuttavia tale differenza sta scomparendo e questo è da attribuire l’aumento dell’abitudine al fumo di sigaretta nelle donne nel corso degli ultimi decenni. La principale causa della BPCO è il fumo di sigaretta e pertanto l’unico intervento efficace per rallentare la progressione della malattia, è l’abolizione del fumo.

2002 - Pathology of COPD and asthma [Capitolo/Saggio]
S., BARALDO S; Beghe', Bianca; R., Zuin; M., Saetta
abstract

2001 - Diagnosis in adults. [Capitolo/Saggio]
A. L., Cogo; Beghe', Bianca; L., Corbetta; Fabbri, Leonardo
abstract

Asthma is a syndrome characterized by recurrent respiratory symptoms, i.e. dyspnoea, wheezing, chest tightness or cough associated with reversible airflow limitation. Familiar predisposition, atopy, and exposure to allergen and sensitising agents are important risk factors for asthma, even the causes of asthma, meaning the factors responsible of the new cases of asthma instead of the exacerbations of asthma, remain largely undetermined

2001 - Genetic influences on Asthma Severity. [Capitolo/Saggio]
J. W., Holloway; S., Rorke; Beghe', Bianca; S. T., Holgate
abstract

In recent years asthma-related morbidity and mortality has increased globally. In the northern area of Spain the average total annual asthma–derived cost was estimated at US$2,879 per patient with costs increasing according to the grade of severity to as much as US$ 6,393 per patient in the case of severe asthma [1]. Given the social and economic impact of severe asthma, it is essential that the underlying determinants of asthma severity are understood. It is well established that there is a strong genetic component underlying susceptibility to asthma, but few studies have addressed whether there are genetic factors that modify severity of disease. While there is some evidence that severity of asthma is heritable, and association between measures of severity and polymorphism in candidate genes have been identified, the identification of genetic factors contributing to asthma severity has been hampered by the lack of clear, easily applied, accurate phenotype definitions for asthma severity that distinguish between underlying severity and level of therapeutic control. The development of such phenotypes in conjunction with more extensive studies of the genetics of asthma severity may allow identification of at risk individuals, and targeting of prophylactic therapy.

2001 - Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families. [Articolo su rivista]
J. W., Holloway; C., Lonjou; Beghe', Bianca; Q., Peng; T. R., Gaunt; I., Gomes; I. P., Hall; J. C., Dewar; J., Wilkinson; N. S., Thomas; S. T., Holgate; N. E., Morton
abstract

Atopy and asthma are complex genetic diseases resulting from the interactions of a number of genetic and environmental factors. We had previously reported allelic association between the IL9 marker on chromosome 5q31-33 and atopy. In order to further investigate the role of susceptibility genes on 5q31-33 in the development of atopy and asthma we have studied 240 UK families comprising 131 families selected at random, 60 multiplex families with affected sib pairs, and 49 single proband nuclear families. Polymorphic markers on 5q31-33 were genotyped and both single and multipoint linkage analysis was undertaken using the BETA program. We have used both affection status and quantitative scores for atopy and asthma for phenotypic variables, combining data into scores for asthma and atopy. The strongest suggestion of linkage using multipoint analysis was centred around D5S410 with a maximum Lod of 1.946 at location 171.3 cM and a standard error of 3.3 for the asthma quantitative score. There was no evidence of linkage with atopy, the atopy quantitative score or total serum IgE.

2001 - Trattamento farmacologico dell’asma bronchiale. [Capitolo/Saggio]
Beghe', Bianca; A., Papi; I., Guzzinati; Fabbri, Leonardo
abstract

L’asma bronchiale può essere tenuto efficacemente sotto controllo, anche se non può essere guarito, facendo un uso appropriato dei farmaci disponibili. Scopo della terapia è quindi il controllo dell’asma, che consiste nel raggiungere alcuni obbiettivi:rendere il paziente asintomatico,prevenire le riacutizzazioni di asma, e quindi ridurre al minimo il ricorso ai broncodilatatori;normalizzare il quadro funzionale respiratorio, comunque portarlo ai migliori valori possibili; consentire al paziente un normale stile di vita, ivi compresa la normale attività fisica, anche sportiva; rdurre al minimo gli effetti collaterali dei farmaci somministrati.

2000 - Association between HLA genes and susceptibility to toluene diisocyanate-induced asthma [Articolo su rivista]
C. E., Mapp; Beghe', Bianca; A., Balboni; G., Zamorani; M., Padoan; L., Jovine; O. R., Baricordi; Fabbri, Leonardo
abstract

BACKGROUND: Only a small proportion of subjects exposed to isocyanates develop occupational asthma, suggesting individual predisposition. The human leucocyte antigen (HLA) class II molecules may play a crucial role in the development of the immune response to isocyanates.OBJECTIVES: To investigate the role of HLA class II molecules in the development of toluene diisocyanate (TDI)-induced asthma.SUBJECTS: Sixty-seven asthmatic subjects and 27 asymptomatic exposed subjects (controls) were typed at the HLA class II DQA1, DQB1 and DRB1 loci by polymerase chain reaction (PCR)-based techniques.RESULTS: The frequencies of DQA1*0104 and DQB1*0503 were significantly increased in asthmatics compared with asymptomatic exposed subjects, while DQA1*0101 and DQB1*0501 were significantly increased in asymptomatic exposed subjects. No significant difference was found in the distribution of DRB1 alleles between asthmatics and controls.CONCLUSIONS: The results of this study indicate that HLA-regulated immune mechanisms are involved in TDI-induced asthma and that, in exposed subjects, specific factors may increase or decrease the risk of developing disease

2000 - MADGE and other single nucleotide polymorphism analysis methods: application to molecular genetic epidemiology of asthma and cardivascular disease. In . 2000:35-48. [Capitolo/Saggio]
J., Sayers; Ye X., Hchen; Beghe', Bianca; I. N. M., Day
abstract

2000 - Trattamento farmacologico dell’asma bronchiale [Capitolo/Saggio]
Beghe', Bianca; Papi, A; I., Guzzinati; Fabbri, Leonardo
abstract

1999 - Comparison of three methods for single nucleotide polymorphism typing for DNA bank studies: sequence-specific oligonucleotide probe hybridisation, TaqMan liquid phase hybridisation, and microplate array diagonal gel electrophoresis (MADGE). [Articolo su rivista]
J. W., Holloway; Beghe', Bianca; S., Turner; L. J., Hinks; I. N., Day; W. M., Howell
abstract

In the near future the number of SNPs identified and mapped will increase and the need for high throughput SNP typing will be paramount for comprehensive examination by association of the role of genomic regions in disease traits. A range of higher throughput methods for typing SNPs is now in routine use in many laboratories worldwide. In this report, we analyse the relative advantages and disadvantages of three such methods, TaqMan, PCR-SSOP, and ARMS-MADGE, currently in use in our laboratories. Throughputs achievable are similar, but there are major differences in cost and time for set-up, equipment, consumables, and staff time, which may determine the choice for individual laboratories.

1999 - The genetic basis of atopic asthma. [Articolo su rivista]
J. W., Holloway; Beghe', Bianca; S. T., Holgate
abstract

Asthma is a respiratory disease characterized by recurrentrespiratory symptoms, reversible variable airway obstruction,airway inflammation and increased airway responsiveness. Atopy is a disorder involving immunoglobulin E(IgE) antibody responses to ubiquitous allergens, and iscommonly associated with asthma. Because of its complexclinical phenotype, the genetic basis of asthma can bestudied using intermediate or surrogate phenotypes thatcan be measured objectively, such as the presence ofatopy or bronchial hyperresponsiveness (BHR), althoughthese are not specific to asthma. Furthermore, despite theclose relationship between atopy, bronchial hyperresponsivenessand asthma, they are not interchangeable:most asthmatics are atopic, but atopic subjects may not havebronchial hyperresponsiveness or asthma symptoms andsubjects with bronchial hyperresponsiveness may not beatopic or asthmatic. The phenotype can bedefined in several ways ranging from subjective measures(e.g. symptoms), objective measures (e.g. BHR or serumIgE level) or both. It is this lack of a clear definition ofasthmatic phenotypes that presents the biggest problemwhen reviewing studies of the genetic basis of asthma andatopy, with multiple definitions of the same intermediatephenotype being used in different studies.

1998 - CHRONIC OBSTRUCTIVE PULMOARY DISEASE INTERNATIONAL GUIDELINES [Articolo su rivista]
Fabbri, Leonardo; G., Caramori; Beghe', Bianca; A., Papi; A., Ciaccia
abstract

Although chronic obstructive pulmonary disease (COPD) has a public health importance similar to asthma, it has received less attention. The first guideline on the management of COPD was released in 1987 by the American Thoracic Society. In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the European Respiratory Society and the Thoracic Society of Australia and New Zealand released their guidelines and the American Thoracic Society updated and expand its COPD guidelines. All these documents were followed in 1997 by the guidelines developed by the British Thoracic Society. These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies. Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research.

1998 - Chronic obstructive pulmonary disease international guidelines [Articolo su rivista]
Beghe', Bianca
abstract

1998 - Comparison of two methods of processing induced sputum: Selected versus entire sputum (multiple letters) [Articolo su rivista]
Belda, J.; Parameswaran, K.; Hargreave, F. E.; Spanevello, A.; Beghe', Bianca.; Ind, P. W.
abstract

1998 - Comparison of two methods of processing induced sputum: selected versus entire sputum. [Articolo su rivista]
A., Spanevello; Beghe', Bianca; A., Bianchi; G. B., Migliori; M., Ambrosetti; M., Neri; P. W., Ind
abstract

Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3\%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8\%; p < 0.01), and higher levels of ECP (548 versus 105 microg/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3\%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects.

1998 - Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease. [Articolo su rivista]
M., Confalonieri; E., Mainardi; R., Della Porta; S., Bernorio; L., Gandola; Beghe', Bianca; A., Spanevello
abstract

BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27\%) and total cells (-42\%) with respect to baseline, while the control group did not (neutrophils +9\%, total cells +7\%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52\% in the treated group and 73.3\% in the control group (95\% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8\% in treated group and 19.3\% in control group (95\% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3\%), macrophages (+16.5\%), and total cells (-65\%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.

1998 - Intrinsic asthma. Lung Biology in Health and Disease. [Capitolo/Saggio]
Fabbri, Leonardo; G., Caramori; Beghe', Bianca; C., Mapp
abstract

1998 - Physiologic consequences of long term inflammation [Articolo su rivista]
L. M., Fabbri; G., Caramori; Beghe', Bianca; A., Papi; A., Ciaccia
abstract

The most recent guidelines for asthma (1–4) emphasize theneed for future research into several unexplored or poorly exploredareas of asthma. One of these areas is the natural historyof asthma, particularly the natural history and the physiologicconsequences of asthmatic bronchopulmonary inflammation.This review will consider the evidence that asthma is a diseaseassociated with both an exaggerated decline in lung functionand an increase in mortality, the relationship of airway inflammationas we understand it to such events, and the potentialfor early therapeutic intervention to modify the disease process.

1998 - Similarities and discrepancies between exacerbations of asthma and chronic obstructive pulmonary disease. [Articolo su rivista]
Fabbri, Leonardo; Beghe', Bianca; G., Caramori; A., Papi; M., Saetta
abstract

Asthma is a chronic inflammatory disorder ofthe airways which causes recurrent episodes ofwheezing, breathlessness, chest tightness, andcough, symptoms which are usually associatedwith reversible airflow limitation.1 2 This definitionincludes the recurrence of respiratorysymptoms which might be otherwise classifiedas asthma exacerbations. However, the termasthma exacerbation is usually reserved formore severe and/or more persistent respiratorysymptoms requiring a prolonged increase ofcurrent antiasthma medication.1 2 Chronic obstructivepulmonary disease (COPD) is definedas a progressive airflow limitation, mostlyirreversible.3 4 The term COPD includes patientswith obstructive chronic bronchitisand/or pulmonary emphysema.3 4 Patients withmoderate or severe persistent asthma may alsohave an irreversible component of airflow limitation,and thus they may also be included inthe definition of COPD.3 The definition ofCOPD does not include exacerbations,3–5 evenif exacerbations are the main cause of medicalintervention and admission to hospital in thesepatients.

1997 - Il futuro nella terpia dell'asma [Capitolo/Saggio]
Beghe', Bianca; G., Caramori; A., Ciaccia; Fabbri, Leonardo
abstract

L'asma (parola greca che significa "senza respiro" o respiro a bocca aperta") è una malattia infiammatoria cronica delle vie aeree, specificamente caratterizzata da infiltrazione di eosinofili, mastociti e linfociti T attivati e da fibrosi subepiteliale della mucosa tracheobronchiale. Tali alterazioni anatomopatologiche costituiscono il substrato dell'iperresponsività bronchiale e dei ricorrenti episodi di ostruzione del reversibile flusso aereo.La dimostrazione che l'asma non è solo l'espressione di ricorrenti crisi di broncospasmo ma è, anche in fase quiescente, una malattia infiammatoria cronica delle vie aeree, ha imposto un cambiamento radicale all'approccio terapeutico. La moderna terapia antiasmatica a lungo termine consiste di un prolungato trattamento di fondo con glucocorticoidi per via inalatoria o, in alcuni casi, con cromoni per via inalatoria, e di un trattamento sintomatico con farmaci broncodilatatori per via inalatoria, in particolare i beta2 agonisti, prescritti solo per rimuovere i sintomi o per prevenire riacutizzazioni asmatiche causate da stimoli noti quali l'attività fisica.

1997 - Semi-quantitative assessment of 99Tcm-sestamibi uptake in lung cancer: relationship with clinical response to chemoterapy [Articolo su rivista]
L., Ceriani; L., Giovanella; M., Bandera; Beghe', Bianca; M., Ortelli; G., Roncari
abstract

The objectives of this study were to measure semi-quantitatively uptake of 99Tcm-sestamibi (99Tcm-MIBI) by tumour tissue in patients with lung cancer and to investigate its relationship with clinical response to chemotherapy. 99Tcm-MIBI single photon emission tomography was performed at the time of diagnosis in 31 patients with biopsy-proven lung cancer (19 small cell carcinomas, 12 non-small cell carcinomas), all of whom were undergoing chemotherapy. Fifteen patients were also investigated 2 weeks after the first and third cycles of chemotherapy. To quantify 99Tcm-MIBI uptake, a tumour/lung (T/L) ratio was calculated for the tomographic slices. The response to chemotherapy was rated as complete remission, partial remission or no remission using dimensional criteria. The results were expressed as the median and inter-quartile range; non-parametric statistical analyses were used. Forty one neoplastic localizations (31 primary tumours and 10 hilar or mediastinal lymph node masses) were assessed. The median T/L ratio of the primary tumours was 1.85 (range 1.7-2.4). Patients with a different response to chemotherapy had a significantly different median T/L ratio before chemotherapy: complete remission (n = 8), T/L ratio = 2.95 (range 2.20-3.25); partial remission (n = 10), 2.15 (range 1.77-2.40); no remission (n = 13), 1.70 (range 1.47-1.75) (Kruskal-Wallis, P < 0.0001). A T/L ratio of 1.80 gave sensitivity of 83\%, specificity of 85\% and accuracy of 84\% in the prediction of the response to chemotherapy. The patients with small cell carcinomas demonstrated greater 99Tcm-MIBI uptake than those with non-small cell carcinomas: T/L ratio, median 2.30 (range 1.76-3.00) vs 1.70 (range 1.50-1.78) (Mann-Whitney U-test, P = 0.001). No significant difference in 99Tcm-MIBI uptake was observed between the 10 lymph node metastases and the corresponding primary tumours: T/L ratio, median 2.30 (range 1.75-2.50) vs 2.15 (1.77-3.00) (Wilcoxon's paired samples rank test, N.S.). Of the 15 patients who were monitored with scintigraphy during chemotherapy, 10 showed complete or partial remission and a parallel reduction in their T/L ratio. The other five patients showed no response to chemotherapy and their T/L ratio was either unaffected or increased. We conclude that the semi-quantitative assessment of 99Tcm-MIBI uptake may have a significant role to play in the management of lung cancer, providing an effective means of predicting the efficacy of chemotherapy and of selecting subgroups of patients requiring radiotherapy or combined protocols before the start of treatment. 99Tcm-MIBI imaging may also be of use in monitoring clinical response to chemotherapy.

1996 - La scoperta dell’ossido nitrico endogeno ha aperto nuove prospettive terapeutiche nella patologia polmonare dell’adulto? [Articolo su rivista]
Fabbri, Leonardo; Cremona, G; Caramori, G; Piattella, M; Romagnoli, M; Beghe', Bianca; Panella, Gl; Ciaccia, A.
abstract

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1996 - Role of leukotrienes in asthma pathogenesis. [Articolo su rivista]
Fabbri, Leonardo; G., Caramori; Beghe', Bianca; A., Ciaccia
abstract

Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid, are pro-inflammatory mediators with various biological activities, including mechanisms relevant to the pathogenesis of bronchoobturation in bronchial asthma. This article reviews the evidence on their role in the pathophysiology of asthma as well as on the efficacy of recently developed antileukotriene agents.

1995 - Evaluation of the serum markers CEA, NSE, TPS and CYFRA 21.1 in lung cancer. [Articolo su rivista]
L., Giovanella; L., Ceriani; M., Bandera; Beghe', Bianca; G., Roncari
abstract

We investigated the role of tumor markers CEA, NSE, TPS and CYFRA 21.1 in lung cancer diagnosis and staging in 169 patients with histologically confirmed lung cancer (43 SCLC and 126 NSCLC). In SCLC patients NSE and CYFRA 21.1 showed the highest sensitivity and their combination improve significantly the diagnostic sensitivity and accuracy. In NSCLC patients CYFRA 21.1 showed the highest sensitivity and global accuracy and no markers association was as effective as CYFRA 21.1 alone. Based on data from our study it can be concluded that in patients with suspected lung cancer the serum NSE and CYFRA 21.1 assay is a suitable association to confirm the clinical hypothesis. NSE in SCLC and CYFRA 21.1 in NSCLC are useful in the evaluation of disease extent and successive treatment planning.

1995 - Tissue polypeptide specific antigen (tps) and cytokeratin 19 fragment (CYFRA 21.1) immunoradiometric assay in non small cell lung cancer evaluation. [Articolo su rivista]
L., Giovanella; L., Ceriani; M., Bandera; R., Rimoldi; Beghe', Bianca; G., Roncari
abstract

The aim of our work was the evaluation of the immunoradiometric assay (IRMA) of two cytokeratinic markers, TPS and CYFRA 21.1, in clinical setting on non small cell lung cancer (NSCLC). Serum samples were obtained from 148 untreated NSCLC patients, 60 patients with non malignant lung diseases and 100 healthy subjects: TPS and CYFRA 21.1 serum levels were assayed by IRMA methods. Diagnostic performance of the markers was evaluated and the TPS and CYFRA 21.1 distribution analysed according to some different clinical and biological variables as histological subtypes, stage and survival time by using the Mann-Whitney "U"-test. Sensitivity, specificity and accuracy were 0.54 (80/148), 0.47 (28/60), 0.52 (108/208) and 0.73 (108/148), 0.74 (44/60), and 0.73 (152/208) for TPS and CYFRA 21.1 respectively. CYFRA 21.1 demonstrate a higher sensitivity than TPS in all stages of the disease and in the spinocellular and adenocarcinoma histological subtypes while TPS sensibility is higher in large cell carcinoma. The CYFRA 21.1 specificity is better than TPS probably by reason of its preferential distribution in respiratory epithelium. Both markers serum levels differ significantly between Stage I-II and IV and between Stage I-II-IIIa and IIIb-IV but neither TPS nor CYFRA 21.1 can discriminate Stage IIIa from IIIb. No significant differences were found in the serum expression of the markers by the different histological subtypes. A value of both markers less than the selected cut-off is related to a longer survival of the patients apart from therapy (p < 0.05). Our conclusion supports similar behaviour of these markers in NSCLC and indicates CYFRA 21.1 as the more needed biochemical index to evaluate NSCLC patients.

1993 - Some remarks on ambulatory activity of respiratory allergology in the city of Varese [Articolo su rivista]
Beghe', Bianca
abstract

From January 1990 to December 1992 we visited 3282 outpatients in the Allergology Unit of Pneumology Department in Varese Regional Hospital. As a first line assessment in 1895 patients we made prick tests. We found a positive prick almost to one allergen in 1080 patients. Here we report our findings about age of symptoms onset, history of atopy, allergen sensitivity, treatments, etc. In 320 patients (30%) we proposed specific immunotherapy. In our opinion specific immunotherapy should be done by trained medical personnel.

Università degli studi di Modena e Reggio Emilia

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