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Stefania CERRI
Ricercatore t.d. art. 24 c. 3 lett. B
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico
Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico
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Pubblicazioni
2024
- Proteomics Analysis of Formalin-Fixed Paraffine-Embedded Tissue Reveals Key Proteins Related to Lung Dysfunction in Idiopathic Pulmonary Fibrosis.
[Articolo su rivista]
Samarelli, ANNA VALERIA; Tonelli, Roberto; Raineri, Giulia; Bruzzi, Giulia; Andrisani, Dario; Gozzi, Filippo; Marchioni, Alessandro; Costantini, Matteo; Fabbiani, Luca; Genovese, Filippo; Pinetti, Diego; Manicardi, Linda; Castaniere, Ivana; Masciale, Valentina; Aramini, Beatrice; Tabbi', Luca; Rizzato, Simone; Bettelli, Stefania; Manfredini, Samantha; Dominici, Massimo; Clini, Enrico; Cerri, Stefania
abstract
Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal
stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations
to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of
archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. We further determined the protein expression
according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients
compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic
analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. After the
pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that
were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor β (TGF‐β) signaling
pathways strongly associated with IPF onset and progression. Five proteins were significantly over-expressed in the lung of IPF
patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLco<55) compared to controls;
these were lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan
(OGN) that might play a key role in the fibrogenic processes. Our work showed that the analysis of FFPE samples was able to
identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or
involved in the immune landscape of lung cancer, thus making possible common mechanisms between lung carcinogenesis and
fibrosis progression, two pathological conditions at risk for each other in the real life.
2024
- When sarcoidosis hits down: a case of prostatic sarcoidosis.
[Articolo su rivista]
Moretti, Antonio; Bruzzi, Giulia; Andrisani, Dario; Gozzi, Filippo; Costantini, Matteo; Tonelli, Roberto; Clini, Enrico; Cerri, Stefania
abstract
A 69-year-old North African male with established diagnosis of sarcoidosis underwent a stereotactic prostate biopsy with fusion technique. At the histological analysis, non-necrotizing microgranulomas were highlighted in 2 samples, while the immunohistochemical staining resulted negative for CK903/p63/racemase. To the best of our knowledge, only 16 cases of prostatic sarcoidosis have been reported in literature. With this case report we describe an incidental diagnosis of prostatic involvement of sarcoidotic disease and briefly review and discuss the available literature on the topic.
2023
- Bronchiectasis as long-term complication of acute fire smoke inhalation?
[Articolo su rivista]
Rizzato, Simone; Tacconi, Matteo; Andrisani, Dario; Luppi, Fabrizio; Clini, Enrico; Cerri, Stefania
abstract
In this letter to editor, we discuss the occurrence of radiological and clinical evidence of bronchiectasis syndrome three years after acute exposure to fire smoke in a Caucasian non-smoker asthmatic patient.
2023
- Covid-19, a new possible mimicker of interstitial lung disease related to primary Sjögren’s syndrome: a case report.
[Articolo su rivista]
Laneri, Alessia; Cerri, Stefania; DELLA CASA, Giovanni; Moretti, Antonio; Manfredi, Andreina; Sebastiani, Marco; Clini, Enrico; Salvarani, Carlo
abstract
Introduction: Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases (CTD).
Case report: In 2018, a 52-year-old woman, was diagnosed with pSS. The patient complained of no respiratory symptoms and a chest x-Ray was normal.
During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest HRCT showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFT) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist didn’t allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A wait and see approach was decided, monitoring clinical conditions, PFTs and chest HRCT over time.
Only 2 years after the hospitalization, a slight improvement of clinical symptoms was reported; PFT also improved; a follow-up HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations.
Discussion: In the above-reported case report, 3 differential diagnoses were possible: a COVID-19 related ILD, a pre-existing pSS-ILD or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations rapidly disappeared after about 2 years.
2023
- Physiological effects of lung protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.
[Articolo su rivista]
Tonelli, Roberto; Grasso, Salvatore; Cortegiani, Andrea; Ball, Lorenzo; Castaniere, Ivana; Tabbì, Luca; Fantini, Riccardo; Andrisani, Dario; Gozzi, Filippo; Moretti, Antonio; Bruzzi, Giulia; Manicardi, Linda; Cerri, Stefania; Samarelli, ANNA VALERIA; Raineri, Giulia; Murgolo, Francesco; Carzoli, Andrea; Di Mussi, Rossella; Busani, Stefano; Rizzoni, Raffaella; Grasselli, Giacomo; Clini, Enrico; Marchioni, Alessandro
abstract
Background- Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung protective ventilation in patients with AE-ILD-UIP compared with primary ARDS.
Methods- Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero=ZEEP, 4-8 cmH2O=PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure-PL,EE=PEEPTITRATED) were used for measurements.
Results- Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [-7.6 – -2.3] cmH2O and lung elastance (EL) 44 [40 – 51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p=0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3 – 1.5] cmH2O and EL to 49 [43 – 59] (p=0.004 and p<0.001 compared to ZEEP and PEEPLOW, respectively). PL decreased at PEEPLOW (p=0.018) and increased at PEEPTITRATED (p=0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and PL.
Conclusions- In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.
2022
- Biological effects of COVID-19 on lung cancer: can we drive our decisions?
[Articolo su rivista]
Aramini, Beatrice; Masciale, Valentina; Samarelli, Anna V.; Tonelli, Roberto; Cerri, Stefania; Clini, Enrico; Stella, Franco; Dominici, Massimo
abstract
COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon
infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC
reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of pro-inflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19.
2022
- Inspiratory effort and respiratory mechanics in spontaneously breathing patients with acute exacerbation of idiopathic pulmonary fibrosis: a retrospective matched control study.
[Articolo su rivista]
Tonelli, Roberto; Castaniere, Ivana; Cortegiani, Andrea; Tabbì, Luca; Fantini, Riccardo; Andrisani, Dario; Gozzi, Filippo; Moretti, Antonio; Bruzzi, Giulia; Manicardi, Linda; Cerbone, Caterina; Nani, Chiara; Biagioni, Emanuela; Cerri, Stefania; Samarelli, Valeria; Busani, Stefano; Girardis, Massimo; Marchioni, Alessandro; Clini, Enrico
abstract
Background- Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking.
Methods- Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive noninvasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔP es ) and respiratory mechanics before and 2 hours after NIV start were collected as primary outcome. Correlation between positive end-expiratory pressure (PEEP) levels and changes of dynamic compliance (dynC RS ) and PaO 2 /FiO 2 ratio was assessed. Further, an exploratory comparison with a historic cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO 2 /FiO 2 level was performed.
Results- At baseline, AE-IPF presented high respiratory drive activation with ΔPes = 27 (21–34) cmH2O, respiratory rate (RR) = 34 (30–39) bpm and minute ventilation (VE) = 21 (20–26) L/min. Two hours after NIV application, ΔPes, RR and VE showed a significant reduction (16 [14–24] cmH2O, p<0.0001, 27 [25–30] bpm, p=0.001, and 18 [17–20] L/min, p=0.003, respectively) while no significant change was found for dynamic transpulmonary pressure (27 [21–34] VS 27 [25–36] cmH2O, p=0.2) expiratory tidal volume (Vte) (9.1 [8.7–10.1] VS 9.3 [8.7 – 9.9] mL/kg of predicted boy weight, p=0.2), dynCRS (28 [19–31] VS 26 [18–28] mL/cmH2O, p=0.1) and dynamic mechanical power (71 [49–94] VS 60 [51–74] J/min, p=0.1). PEEP levels negatively correlated with PaO 2 /FiO 2 ratio and dynC RS (r=–0.67, p=0.03 and r=–0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔP
es , RR, VE and dynamic mechanical power. At difference with AE-IPF, Vte and dynC RS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO 2 /FiO 2 ratio and dynC RS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively).
Conclusions- In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS of similar
severity.
2022
- Pneumopathie interstitielle fibrosante dans le syndrome de Gougerot-Sjögren primitif
[Articolo su rivista]
Manfredi, A.; Vacchi, C.; Della Casa, G.; Cerri, S.; Cassone, G.; Di Cecco, G.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectifs: La pneumopathie interstitielle (PI) représente la principale atteinte pulmonaire dans le syndrome de Gougerot-Sjögren primitif (SGSp). Un certain nombre de patients atteints de SGSp développent une forme fibrosante progressive de PI, mais il n'existe aucune donnée sur la prévalence de telles présentations.L'objectif de cette étude transversale monocentrique était d'explorer la prévalence des formes fibrosantes chez les patients atteints de SGSp présentant une PI. Méthodes: Tous les patients consécutifs remplissant les critères de classification du SGSp et présentant une PI existante ou nouvellement diagnostiquée ont été inclus dans l’étude. Le diagnostic de PI était toujours établi par TDM-HR et les différentes formes ont été déterminées sur la base des critères de classification en vigueur et réparties dans deux groupes selon qu'une forme fibrosante était détectée ou non. Résultats: Trente-quatre patients présentant un SGSp avec PI ont été inclus dans l’étude (3 hommes et 31 femmes, âge médian 69,5 ans, durée moyenne du SGSp 47,5 mois). Une forme fibrosante a été identifiée chez 52,9 % des patients (groupe 1) : pneumopathie interstitielle commune (PIC) chez 13 patients (38,2 %), pneumopathie interstitielle non spécifique (PINS) fibrosante chez 4 patients (11,8 %) et pneumopathie organisée (PO) fibrosante chez 1 patient (2,9 %). Le groupe 2 (16 patients, 47,1 %) comprenait la PINS chez 6 patients (17,6 %), la PO chez 4 patients (11,8 %), la PIL chez 2 patients (5,9 %) et la pneumopathie interstitielle inclassable chez 4 patients (11,8 %). Dans le groupe 1, les patients étaient plus jeunes et la durée du SGSp au moment du diagnostic de PI plus courte. Notamment, la PI a été diagnostiquée avant ou en même temps que le SGSp dans 83,3 % des cas, contre 62,5 % dans le groupe 2 de forme non fibrosante (p < 0,05). Conclusion: Nos données suggèrent une forte prévalence de ce phénotype clinique pulmonaire chez les patients présentant un SGSp avec PI. Compte tenu de l’évolution habituelle des pneumopathies fibrosantes progressives vers une insuffisance respiratoire, ce résultat justifie des études complémentaires.
2022
- The role of immune response in the pathogenesis of idiopathic pulmonary fibrosis: far beyond the Th1/Th2 imbalance.
[Articolo su rivista]
Spagnolo, Paolo; Tonelli, Roberto; Samarelli, ANNA VALERIA; Castelli, Gioele; Cocconcelli, Elisabetta; Petrarulo, Simone; Cerri, Stefania; Bernardinello, Nicol; Clini, Enrico; Saetta, Marina; Balestro., Elisabetta
abstract
Introduction: . Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown origin characterized by progressive scarring of the lung leading to irreversible loss of function. Despite the availability of two drugs that are able to slow down disease progression, IPF remains a deadly disease. The pathogenesis of IPF is poorly understood, but a dysregulated wound healing response following recurrent alveolar epithelial injury is thought to be crucial.
Areas covered. In the last few years, the role of the immune system in IPF pathobiology has been reconsidered; indeed, recent data suggest that a dysfunctional immune system may promote and unfavorable interplay with pro-fibrotic pathways thus acting as a cofactor in disease development and progression. In this article, we review and critically discuss the role of T cells in the pathogenesis and progression of IPF in the attempt to highlight ways in which further research in this area may enable the development of targeted immunomodulatory therapies for this dreadful disease.
Expert opinion: A better understanding of T cells interactions has the potential to facilitate the development of immune modulators targeting multiple T cell-mediated pathways thus halting disease initiation and progression.
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
- Differences between acute exacerbations of idiopathic pulmonary fibrosis and other interstitial lung diseases.
[Articolo su rivista]
Faverio, P; Stainer, A; Conti, S; Madotto, F; De Giacomi, F; Della Zoppa, M; Vancheri, V; Pellegrino, Mr; Tonelli, R; Cerri, S; Clini, E; Mantovani, L; Pesci, A; Luppi, F.
abstract
Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed “acute exacerbation” (AE). Incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian University hospitals from 2009 to 2016. Patients included in the analysis has been divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups, respectively 19% in non-IPF group and 43% in IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers with neutrophilia on differential blood cell count (HR 1.02 [CI 1.01 – 1.04]), presence of pulmonary hypertension (HR 1.85 – [CI 1.17 – 2.92]) and diagnosis of IPF (HR 2.31 [CI 1.55 – 3.46]) resulted negative prognostic factors in our analysis, while lymphocytosis on differential count seemed to act as a protective prognostic factor (OR 0.938 [CI 0.884 – 0.995]). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings.
2021
- Dissecting the role of mesenchymal stem cells in idiopathic pulmonary fibrosis: cause or solution?
[Articolo su rivista]
Samarelli, Av; Tonelli, R; Heijink, I; Martin Medina, A; Marchioni, A; Bruzzi, G; Castaniere, I; Andrisani, D; Gozzi, F; Manicardi, L; Moretti, A; Cerri, S; Fantini, R; Tabbì, L; Nani, C; Mastrolia, I; Weiss, Dj; Dominici, M; Clini, E.
abstract
Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonias, characterized by chronic and progressive fibrosis subverting the lung’s architecture, pulmonary functional decline, progressive respiratory failure, and high mortality (median survival 3 years after diagnosis). Among the mechanisms associated with disease onset and progression, it has been hypothesized that IPF lungs might be affected either by a regenerative deficit of the alveolar epithelium or by a dysregulation of repair mechanisms in response to alveolar and vascular damage. This latter might be related to the progressive dysfunction and exhaustion of the resident stem cells together with a process of cellular and tissue
senescence. The role of endogenous mesenchymal stromal/stem cells (MSCs) resident in the lung in the homeostasis of these mechanisms is still a matter of debate. Although endogenous MSCs may play a critical role in lung repair, they are also involved in cellular senescence and tissue ageing processes with loss of lung regenerative potential. In addition, MSCs have immunomodulatory properties and can secrete anti-fibroticfactors. Thus, MSCs obtained from other sources administered systemically or directly into the lung have been investigated for lung epithelial repair and have been explored as a potential therapy for the treatment of lung diseases including IPF. Given these multiple potential roles of MSCs, this review aims both at elucidating the role of resident lung MSCs in IPF pathogenesis and the role of administered MSCs from other sources for potential IPF therapies.
2021
- Fibrosing interstitial lung disease in primary Sjogren syndrome
[Articolo su rivista]
Manfredi, A.; Vacchi, C.; Dellacasa, G.; Cerri, S.; Cassone, G.; Di Cecco, G.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectives: Interstitial lung disease (ILD) represents the main pulmonary involvement in primary Sjogren syndrome (pSS). A proportion of patients with pSS develop a progressive fibrosing form of ILD, but no data are available about the prevalence of these patterns in pSS patients. Aim of this monocentric, cross-sectional study was to investigate the prevalence of fibrosing patterns in pSS patients with ILD. Methods: All consecutive patients fulfilling classification criteria for pSS with a new or previous diagnosis of ILD were enrolled in the study. Diagnosis of ILD was always performed by mean of HRCT and specific patterns were identified according to current classification criteria and divided in two groups according to the detection of a fibrotic pattern. Results: Thirty-four pSS-ILD patients were enrolled in the study (males/females 3/31, median age 69.5 years, median pSS duration 47.5 months). Fibrotic pattern was detected in 52.9% of patients, namely: UIP (13 patients, 38.2%), fibrotic NSIP (4, 11.8%), fibrotic OP (1 2.9%) and group 2 (16 pts, 47.1%) including NSIP (6, 17.6%), OP (4, 11.8%), LIP (2, 5.9%) and unclassifiable (4, 11.8%). These patients were younger and with a shorter pSS duration at ILD diagnosis, in particular ILD diagnosis was prior or concurrent to pSS in 83.3% of cases compared to 62.5% in the group of nonfibrotic pattern (P < 0.05). Conclusion: Our data suggest a high prevalence of this pulmonary clinical phenotype in pSS-ILD patients. Since the course of progressive fibrosing pneumonia generally results in respiratory failure, this result could be worthy of further studies.
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
- Interstitial lung disease and anti-myeloperoxidase antibodies: not a simple association
[Articolo su rivista]
Sebastiani, Marco; Luppi, Fabrizio; Sambataro, Gianluca; Castillo Villegas, Diego; Cerri, Stefania; Tomietto, Paola; Cassone, Giulia; Bocchino, Marialuisa; Atienza-Mateo, Belen; Cameli, Paolo; Moya Alvarado, Patricia; Faverio, Paola; Bargagli, Elena; Vancheri, Carlo; Gonzalez-Gay, Miguel A; Clini, Enrico; Salvarani, Carlo; Manfredi, Andreina
abstract
Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) 29
antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). 30
However, their role remains unclear and only 7-23% of these patients develops clinically overt vas- 31
culitis. We aimed to investigate the clinical, serological and radiological features, and prognosis of 32
anti-MPO-positive interstitial lung disease (ILD) patients. 33
Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing 34
serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clini- 35
cal data, lung function testing, chest high resolution computed tomography (HRCT) pattern, and 36
survival were recorded. 37
Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual 38
interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the pa- 39
tients’ survival. In fact, while the 52-week survival of the overall population was 71.4%±7.5, signif- 40
icantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. 41
Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7% and 41.5% 42
of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. 43
A careful clinical history and evaluation should be always performed in ILD patients with anti- 44
MPO antibodies to early identify patients developing a systemic rheumatic disease.
2021
- Molecular mechanisms and cellular contribution from lung fibrosis to lung cancer development.
[Articolo su rivista]
Samarelli, ANNA VALERIA; Masciale, Valentina; Aramini, Beatrice; Pamela Colò, Georgina; Tonelli, Roberto; Marchioni, Alessandro; Bruzzi, Giulia; Gozzi, Filippo; Andrisani, Dario; Castaniere, Ivana; Manicardi, Linda; Moretti, Antonio; Tabbì, Luca; Guaitoli, Giorgia; Cerri, Stefania; Dominici, Massimo; Clini, Enrico
abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung 28 disease (ILD) of unknown etiology, with a median survival of 2-4 years from the time of diagnosis. 29 Although IPF has unknown etiology by definition, there have been identified several risks factors 30 increasing the probability of the onset and progression of the disease in IPF patients such as cigarette 31 smoking and environmental risks factors associated to domestic and occupational exposure. Among 32 them, cigarette smoking together with concomitant emphysema might predispose IPF patients to 33 lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer 34 development. To this purpose, IPF and LC share several cellular and molecular processes driving 35 the progression of both pathologies such as fibroblast transition proliferation and activation, endo- 36 plasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose 37 the IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed 38 as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target 39 molecular pathway. In this review our aim is to describe the updated studies on common cellular 40 and molecular mechanisms between IPF and lung cancer, whose knowledge might help to find 41 novel therapeutic targets for this disease combination.
2021
- Pulmonary stretch and lung mechanotransduction: Implications for progression in the fibrotic lung
[Articolo su rivista]
Marchioni, A; Tonelli, R; Cerri, S; Castaniere, I; Andrisani, D; Gozzi, F; Bruzzi, G; Manicardi, L; Moretti, A; Demurtas, J; Baroncini, S; Andreani, A; Cappiello, G; Busani, S; Fantini, R; Tabbì, L; Samarelli, A; Clini, E.
abstract
Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity, surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with as34
sociated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review we aim at summarizing the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.
2021
- Subclinical liver fibrosis in patients with idiopathic pulmonary fibrosis
[Articolo su rivista]
Cocconcelli, E; Tonelli, R; Abbati, G; Marchioni, A; Castaniere, I; Pelizzaro, F; Russo, Fp; Vegetti, A; Balestro, E; Pietrangelo, A; Richeldi, L; Luppi, F; Spagnolo, P; Clini, E; Cerri, S.
abstract
Background - Data on the presence of subclinical fibrosis across multiple organs in patients with idiopathic lung fibrosis (IPF) are lacking. Our study aimed at investigating through hepatic transient elastography (HTE) the prevalence and clinical impact of subclinical liver fibrosis in a cohort of patients with IPF.
Methods - Patients referred to the Centre for Rare Lung Disease of the University Hospital of Modena (Italy) from March 2012 to February 2013with established diagnosis of IPF and without a documented history of liver diseases were consecutively enrolled and underwent HTE. Based on hepatic stiffness status as assessed through METAVIR score patients were categorized as “ with liver fibrosis ” (corresponding to a METAVIR score of F1-F4) and “ without liver fibrosis” (METAVIR F0). Potential predictors of liver fibrosis were investigated through logistic regression
model among clinical and serological variables. The overall survival (OS) was assessed according to liver fibrosis and multivariate Cox regression analysis was used to identify independent predictors.
Results - In 13 out of 37 patients (35%) with IPF a certain degree of liver fibrosis was documented.No correlation was found between liver stiffness and clinical-functional parameters. OS was lower in patients ‘ with liver fibrosis’ than in patients ‘ without liver fibrosis’ (median months 33[23-55] vs. 63[26-94], p=0.038). Patients ‘ with liver fibrosis’ presented a higher risk of death at seven years as compared to patients ‘without liver fibrosis’ (HR=2.6, 95%CI[1.003–6.7],p= 0.049). Higher level of AST to platelet ratio Index (APRI)was an independent predictor of survival (HR=4.52
95%CI[1.3–15.6], p=0.02).
Conclusions - In our cohort, more than one third of IPF patients had concomitant subclinical liver fibrosis that negatively affected OS. These preliminary claims further investigation aimed at clarifying the mechanisms beyond multiorgan fibrosis and its clinical implication in patients with IPF.
2021
- Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis
[Articolo su rivista]
Vacchi, C.; Manfredi, A.; Cassone, G.; Cerri, S.; Della Casa, G.; Andrisani, D.; Salvarani, C.; Sebastiani, M.
abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.
2021
- Usefulness of digital velcro crackles detection in identification of interstitial lung disease in patients with connective tissue diseases
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Vacchi, C.; Pancaldi, F.; Casa, G. D.; Cerri, S.; De Pasquale, L.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectives: This study aims to evaluate the diagnostic accuracy of the VECTOR software in patients with connective tissue diseases (CTDs), compared with the reference standard of high-resolution computed tomography (HRCT). Patients and methods: The study included 98 consecutive patients of CTD (24 males, 74 females; median age: 66 years; range, 24 to 85 years) with a recent HRCT. Patients were evaluated in a blindly manner by VECTOR and the results obtained by the algorithm were compared with the presence of interstitial lung disease (ILD) according to HRCT. Results: Interstitial lung disease was detected in 42.8% of subjects. VECTOR correctly classified 81/98 patients, with a diagnostic accuracy of 82.6%; sensitivity and specificity were 88.1% and 78.6%, respectively. Only 5/42 patients with ILD were not correctly classified by VECTOR, while false positive cases were 21.4%. No significant differences were observed according to the radiologic pattern of ILD. Conclusion: VECTOR showed high sensitivity, specificity and diagnostic accuracy, allowing selecting patients to be investigated with HRCT. The relatively high frequency rate of false positive results is acceptable if compared with the lack of effective screening methods for this complication of CTDs.
2020
- CHARACTERIZATION OF ANTI-MPO POSITIVE INTERSTITIAL LUNG DISEASE. CLINICAL-SEROLOGIC AND RADIOLOGIC FEATURES AND SURVIVAL
[Abstract in Rivista]
Cassone, G; Dei, G; Sambataro, G; Manfredi, A; Cerri, S; Vacchi, C; Faverio, P; Sambataro, D; Gozzi, F; Vancheri, C; Salvarani, C; Luppi, F; Sebastiani, M
abstract
2020
- Combination Therapy with Nintedanib and Sarilumab for the Management of Rheumatoid Arthritis Related Interstitial Lung Disease
[Articolo su rivista]
Vacchi, Caterina; Manfredi, Andreina; Cassone, Giulia; Salvarani, Carlo; Cerri, Stefania; Sebastiani, Marco
abstract
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease characterized by joint and extra-articular involvement. Among them, interstitial lung disease (ILD) is one of the most common and severe extra-articular manifestations, with a negative impact on both therapeutic approach and overall prognosis. ILD can occur at any point of the natural history of RA, sometimes before the appearance of joint involvement. Since no controlled studies are available, the therapeutic approach to RA-ILD is still debated and based on empirical approaches dependent on retrospective studies and case series. Here, we report the case of a 75-year-old patient affected by RA complicated by ILD successfully treated with a combination therapy of an antifibrotic agent, nintedanib, and an inhibitor of IL-6 receptor, sarilumab. We obtained a sustained remission of the joint involvement and, simultaneously, a stabilization of the respiratory symptoms and function, with a good safety profile. To date, this is the first report describing a combination therapy with nintedanib and a disease-modifying antirheumatic drug (DMARD) for the management of RA complicated by ILD. Future prospective studies are needed to better define efficacy and safety of this approach in the treatment of these subjects.
2020
- Erratum: Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: A prospective study and review of the literature (Journal of Thoracic Disease (2019) 11 (1621-1628) DOI: 10.21037/jtd.2019.03.28)
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cerri, S.; Vacchi, C.; Tonelli, R.; Della Casa, G.; Cassone, G.; Spinella, A.; Pancaldi, F.; Luppi, F.; Salvarani, C.
abstract
In the article that appeared on Page 1621-1628, Vol 11, No 4 (April 2019) Issue of the Journal of Thoracic Disease (1), the given and family names of author “Fabrizio Pancaldi” was incorrectly published in the original. The author's name should be corrected as Fabrizio Pancaldi, instead of Pancaldi Fabrizio. The authors regret the error.
2020
- INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. WHAT DO WE DON’T KNOW? THE LIRA STUDY (LUNG INVOLVEMENT IN RHEUMATOID ARTHRITIS)
[Articolo su rivista]
Sebastiani, M.; Vacchi, C.; Cassone, G.; Salvarani, C.; Sandri, G.; Atzeni, F.; Biggioggero, M.; Carriero, A.; Erre, G. L.; Fedele, A. L.; Furini, F.; Tomietto, P.; Venerito, V.; Atienza-Mateo, B.; Della Casa, G.; Cerri, S.; Palermo, A.; Galli, E.; Pancaldi, F.; González-Gay, M. A.; Manfredi on behalf of LIRA Study Group, A.
abstract
Background: Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.
Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.
Objectives: For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.
Methods: All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).
For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.
Results: At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; p<0.0001, female/male ratio 139/23 vs 22/21; p<0.0001) without significant differences regarding disease duration, positivity for ACPA or RF.
Conclusion: The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.
2020
- Interstitial pneumonia with autoimmune features: A single center prospective follow-up study
[Articolo su rivista]
Sebastiani, M.; Cassone, G.; De Pasquale, L.; Cerri, S.; Della Casa, G.; Vacchi, C.; Luppi, F.; Salvarani, C.; Manfredi, A.
abstract
Background and objective: Recently the term “interstitial pneumonia with autoimmune features” (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. The aims of the study were to investigate the demographic and clinico-serologic features of patients with IPAF, their relationship to survival, and the possible evolution in a definite CTD. Patients and methods: Fifty-two patients were consecutively enrolled and prospectively followed for 45 ± 31.6 months. Data about disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. The survival of patients with IPAF was compared with that of 104 patients with idiopathic pulmonary fibrosis (IPF). Results: The clinical domain for IPAF was satisfied in 44 patients, serological domain in 49 and the morphological domain in 29 patients. During the follow-up, a definite CTD was diagnosed in 7 patients, in particular Sjogren's syndrome in 4 patients, rheumatoid arthritis in 2, and polymyositis in the last. The estimated 5-year survival of IPAF patients 69.5 ± 7.8%, significantly higher than survival observed in IPF patients, and the baseline value of FVC and DLCO were the only factors associated to death. Conclusions: IPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.
2020
- Janus-faced amiodarone-induced pneumopathy
[Articolo su rivista]
Cerri, Stefania; Tonelli, Roberto; Faverio, Paola; Sverzellati, Nicola; Clini, Enrico; Luppi, Fabrizio
abstract
The authors describe a patient showing bilateral, peripheral, predominantly basal ground-glass and reticular opacities consistent with a non-specific interstitial pneumonia (NSIP) radiological pattern. This was followed by the occurrence of two nodules that progressively decreased in size after oral steroids had been given and therefore they were interpreted as an unusual manifestation of amiodarone-related pulmonary toxicity (APT).
2020
- Pirfenidone for the treatment of interstitial lung disease associated to rheumatoid arthritis: a new scenario is coming?
[Articolo su rivista]
Cassone, G.; Sebastiani, M.; Vacchi, C.; Cerri, S.; Salvarani, C.; Manfredi, A.
abstract
Introduction: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of Rheumatoid arthritis (RA), but nowadays there are no randomized controlled clinical trials to support therapeutic guidelines. RA-ILD, especially with UIP pattern, shares some similarities with idiopathic pulmonary fibrosis, suggesting a possible role of antifibrotic therapy in these patients. To date, there are no published data supporting the use of pifenidone in RA-ILD. We describe for the first time two patients with a diagnosis of RA-ILD successfully treated with hydroxychloroquine and pirfenidone, without adverse events. Case presentation: Patient 1 and patient 2 were first diagnosed with IPF (UIP pattern at high-resolution computed tomography, no other signs or symptoms suggesting other forms of ILD, routine laboratory examinations and immunological texts negative). Patients started pirfenidone 2403 mg daily. Few months later, they referred to our multidisciplinary outpatient for arthritis. ACPA and RF were positive. A diagnosis of RA was performed and treatment with corticosteroids and hydroxychloroquine was started, in association with pirfenidone. In both cases we assessed the stabilization of articular and lung manifestations, without adverse events. Discussion: In absence of randomized controlled trials, the optimal treatment of RA-ILD has not been determined and remains challenging. When considering therapeutic options for RA-ILD, both pulmonary and extra-thoracic disease manifestations and degrees of activity should be assessed and taken into consideration. Future prospective research might change RA-ILD management, moving to a more personalized approach based on the identification of different phenotypes of the disease or to a combination of immunosuppressive and antifibrotic treatment.
2020
- Therapeutic Options for the Treatment of Interstitial Lung Disease Related to Connective Tissue Diseases. A Narrative Review
[Articolo su rivista]
Vacchi, Caterina; Sebastiani, Marco; Cassone, Giulia; Cerri, Stefania; Della Casa, Giovanni; Salvarani, Carlo; Manfredi, Andreina
abstract
Interstitial lung disease (ILD) is one of the most serious pulmonary complications of connective tissue diseases (CTDs) and it is characterized by a deep impact on morbidity and mortality. Due to the poor knowledge of CTD-ILD's natural history and due to the difficulties related to design of randomized control trials, there is a lack of prospective data about the prevalence, follow-up, and therapeutic efficacy. For these reasons, the choice of therapy for CTD-ILD is currently very challenging and still largely based on experts' opinion. Treatment is often based on steroids and conventional immunosuppressive drugs, but the recent publication of the encouraging results of the INBUILD trial has highlighted a possible effective and safe use of antifibrotic drugs as a new therapeutic option for these subjects. Aim of this review is to summarize the available data and recent advances about therapeutic strategies for ILD in the context of various CTD, such as systemic sclerosis, idiopathic inflammatory myopathy and Sjogren syndrome, systemic lupus erythematosus, mixed connective tissue disease and undifferentiated connective tissue disease, and interstitial pneumonia with autoimmune features, focusing also on ongoing clinical trials.
2020
- Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicenter retrospective study
[Articolo su rivista]
Manfredi, Andreina; Cassone, Giulia; Furini, Federica; Gremese, Elisa; Venerito, Vincenzo; Atzeni, Fabiola; Arrigoni, Eugenio; Della Casa, Giovanni; Cerri, Stefania; Govoni, Marcello; Petricca, Luca; Iannone, Florenzo; Salvarani, Carlo; Sebastiani, Marco
abstract
Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated.
2020
- Unusual effectiveness of systemic steroids in Whipple disease.
[Articolo su rivista]
Fontana, Matteo; Cerri, Stefania; Bernardelli, Giuditta; Brugioni, Lucio; Clini, Enrico; Tonelli, Roberto.
abstract
Not available
2020
- Ventilatory support and mechanical properties of the fibrotic lung acting as a “squishy ball”
[Articolo su rivista]
Marchioni, Alessandro; Tonelli, Roberto; Rossi, Giulio; Spagnolo, Paolo; Luppi, Fabrizio; Cerri, Stefania; Cocconcelli, Elisabetta; Pellegrino, Maria Rosaria; Campana, Davide; Fantini, Riccardo; Tabbì, Luca; Castaniere, Ivana; Ball, Lorenzo; Malbrain, Manu L. N. G.; Pelosi, Paolo; Clini, Enrico
abstract
Protective ventilation is the cornerstone of treatment of patients with the acute respiratory distress syndrome (ARDS); however, no studies have yet established the best ventilatory strategy to adopt when patients with acute exacerbation of interstitial lung disease (AE-ILD) are admitted to the intensive care unit. Due to the severe impairment of the respiratory mechanics, the fibrotic lung is at high risk of developing ventilator-induced lung injury, regardless of the lung fibrosis etiology. The purpose of this review is to analyze the effects of mechanical ventilation in AE-ILD and to increase the knowledge on the characteristics of fibrotic lung during artificial ventilation, introducing the concept of “squishy ball lung”. The role of positive end-expiratory pressure is discussed, proposing a “lung resting strategy” as opposed to the “open lung approach”. The review also discusses the practical management of AE-ILD patients discussing illustrative clinical cases.
2019
- AB0472 PRIMARY SJOGREN SYNDROME ASSOCIATED INTERSTITIAL LUNG DISEASE: FEATURES, TREATMENT AND OUTCOME OF A MONOCENTRIC COHORT
[Abstract in Rivista]
Manfredi, Andreina; Sebastiani, Marco; Vacchi, Caterina; Luppi, Fabrizio; Cerri, Stefania; Cassone, Giulia; Salvarani, Carlo
abstract
2019
- AB1157 VALIDATION OF VECTOR (VELCRO CRACKLES DETECTOR) FOR THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH CONNECTIVE TISSUE DISEASES
[Abstract in Rivista]
Manfredi, Andreina; Cassone, Giulia; Pancaldi, Fabrizio; Vacchi, Caterina; Cerri, Stefania; Casa, Giovanni Della; Salvarani, Carlo; Sebastiani, Marco
abstract
2019
- Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: A prospective study and review of the literature
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cerri, S.; Vacchi, C.; Tonelli, R.; Casa, G. D.; Cassone, G.; Spinella, A.; Pancaldi, Fabrizio; Luppi, F.; Salvarani, C.
abstract
Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It’s defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12–36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease.
2019
- Antifibrotic treatment response and prognostic predictors in patients with idiopathic pulmonary fibrosis and exposed to occupational dust
[Articolo su rivista]
Casillo, V.; Cerri, S.; Ciervo, A.; Stendardo, M.; Manzoli, L.; Flacco, M. E.; Manno, Mauro; Bocchino, M.; Luppi, F.; Boschetto, P.
abstract
BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12 month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. METHODS: A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12 month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean = 37.85, range 12-60 months). RESULTS: At baseline, patients exposed to occupational dust [≥ 10 years (n = 62)] showed a lower percentage of graduates (19.3% vs 54.7%; p = 0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [< 10 years (n = 53)]. Both at diagnosis and after 12 months of antifibrotics, no significant differences for respiratory function and prognostic predictors were found. The multivariate analysis confirmed that occupational dust exposure did not affect neither FVC and DLCO after 12 month therapy nor the timing of LTOT initiation. CONCLUSION: Occupational dust exposure lasting 10 years or more does not seem to influence the therapeutic effects of antifibrotics and the prognostic predictors in patients with IPF.
2019
- Clinical differences in sarcoidosis patients with and without lymphoma: a single-center retrospective cohort analysis.
[Articolo su rivista]
Cerri, Stefania; Fontana, Matteo; Balduzzi, Sara; Potenza, Leonardo; Faverio, Paola; Luppi, Mario; Damico, Roberto; Spagnolo, Paolo; Clini, Enrico; Luppi, Fabrizio
abstract
We retrospectively reviewed the database of the “Center for Rare Lung Diseases” at the University Hospital of Modena to identify all subjects with a diagnosis of sarcoidosis between 1990 and 2013, with the aim to evaluate clinical, functional and serological differences related to the presence of lymphoma in sarcoidosis patients, as well as difference in survival.
This study suggests the existence of clinical, radiological and serological differences in sarcoidosis with or without lymphoma syndrome. The knowledge of these differences seems important for a timely diagnosis and treatment. However, further prospective studies are required to confirm present observations.
2019
- Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: The InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device)
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Cerri, S.; Venerito, V.; Fedele, A. L.; Trevisani, M.; Furini, F.; Addimanda, O.; Pancaldi, F.; Della Casa, G.; D'Amico, R.; Vicini, R.; Sandri, G.; Torricelli, P.; Celentano, I.; Bortoluzzi, A.; Malavolta, N.; Meliconi, R.; Iannone, F.; Gremese, E.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.
2019
- Do not forget to assess the muscle integrity in COPD patients.
[Articolo su rivista]
Cerri, S; Clini, E.
abstract
Not available
2019
- FRI0613 THERAPEUTIC STRATEGIES AND SURVIVAL IN PATIENTS WITH INTERSTITIAL PNEUMONIA WITH AUTOIMMUNE FEATURES
[Abstract in Rivista]
Sebastiani, Marco; Vacchi, Caterina; Pasquale, Lisa De; Cerri, Stefania; Cassone, Giulia; Casa, Giovanni Della; Garofalo, Martina; Salvarani, Carlo; Manfredi, Andreina
abstract
2019
- Real-life comparison of Pirfenidone and Nintedanib in patients with Idiopathic Pulmonary Fibrosis: a 24-month assessment.
[Articolo su rivista]
Cerri, Stefania; Monari, Matteo; Guerrieri, Aldo; Donatelli, Pierluigi; Bassi, Ilaria; Garuti , Martina; Luppi, Fabrizio; Betti, Sara; Bandelli, Giampiero; Carpano , Marco; Bacchi-Reggiani, Marialuisa; Tonelli, Roberto; Clini, Enrico; Nava, Stefano.
abstract
Background: Real-life data on the use of pirfenidone and nintedanib to treat patients with idiopathic pulmonary fibrosis (IPF) are still scarce.
Methods: We compared the efficacy of either pirfenidone (n=78) or nintedanib (n=28) delivered over a 24-month period in patients with IPF, followed at two regional clinic centers in Italy, with a group of patients who refused the treatment (n=36), and who were considered to be controls. All patients completed regular visits at 1- to 3-month intervals, where primary [forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)] and secondary outcomes (side effects, treatment compliance, and mortality) were recorded.
Results: Over time, the decline in FVC and DLCO was significantly higher (p=0.0053 and p=0.037, respectively) in controls when compared with the combined treated group, with no significant difference between the two treated groups. Compared to patients with less advanced disease (GAP (Gender, Age, Physiology) stage I), those in GAP stages II and III showed a significantly higher decline in both FVC and DLCO irrespective of the drug taken. Side effects were similarly reported in patients receiving pirfenidone and nintedanib (5% and 7%, respectively), whereas mortality did not differ among the three groups.
Conclusion: This real-life study demonstrated that both pirfenidone and nintedanib were equally effective in reducing the decline of FVC and DLCO versus non-treated patients after 24 months of treatment; however, patients with more advanced disease were likely to show a more rapid decline in respiratory function.
2019
- Serial Ultrasound Assessment of Diaphragmatic Function and Clinical Outcome in Patients with Amyotrophic Lateral Sclerosis.
[Articolo su rivista]
Fantini, Riccardo; Tonelli, Roberto; Castaniere, Ivana; Tabbì, Luca; Pellegrino, Maria Rosaria; Cerri, Stefania; Livrieri, Francesco; Giaroni, Francesco; Monelli, Marco; Ruggieri, Valentina; Fini, Nicola; Mandrioli, Jessica; Clini, Enrico; Marchioni, Alessandro; Stefania, Cerri
abstract
Background: Ultrasound (US) evaluation of the diaphragm may be a non-volitional useful tool in the clinical management of patients with ALS. Aim of the present study was then to evaluate the impact of serial assessment of ΔTmax index on clinical outcomes during the follow-up in these patients and to correlate non-volitional US indices and other volitional measures with these outcomes.
Methods: A cohort of 39 consecutive patients with ALS was followed up to 24 months. At baseline and every 3-month spirometry (forced vital capacity-FVC), sniff inspiratory nasal pressure (SNIP), and US of the diaphragm (ΔTdi and ΔTmax) were recorded. These parameters were correlated with clinical outcomes (hypercapnia, nocturnal hypoventilation, NIV start in the following 6 month, and death within 1 year).
Results: The occurrence of ΔTmax >0.75 during follow-up increased the risk for NIV (HR=5.6, p=0.001) and death (HR=3.7, p=0.0001) compared with patients with stable lower values. The evidence of diaphragmatic dysfunction, i.e. ΔTmax >0.75, occurs 3.2 month earlier than the onset of NIV. Moreover, ΔTmax >0.75 correlated with onset of nocturnal hypoventilation, NIV initiation within 6 months, and death within 12 months, similarly to FVC <50% predicted and better than other functional indices.
Conclusions: Serial monitoring of diaphragmatic ΔTmax by US may be useful to predict initiation of NIV and death in patients with ALS. The occurrence of an abnormal ΔTmax value in the follow-up precedes the decision for starting NIV.
2019
- The prognostic role of Gender-Age-Physiology system in idiopathic pulmonary fibrosis patients treated with pirfenidone
[Articolo su rivista]
Harari, S.; Caminati, A.; Confalonieri, M.; Poletti, V.; Vancheri, C.; Pesci, A.; Rogliani, P.; Luppi, F.; Agostini, C.; Rottoli, P.; Sanduzzi Zamparelli, A.; Sebastiani, A.; Della Porta, R.; Salton, F.; Messore, B.; Tomassetti, S.; Rosso, R.; Biffi, A.; Puxeddu, E.; Cerri, S.; Cinetto, F.; Refini, R. M.; Bocchino, M.; Di Michele, L.; Specchia, C.; Albera, C.
abstract
Introduction: Gender, age, physiology (GAP) system have proven to be an easy tool for predicting disease stages and survival in idiopathic pulmonary fibrosis (IPF) patients. Objective: To validate mortality risk as determined by the GAP system in a real-life multicentre IPF population treated with pirfenidone. Methods: The study included patients who received pirfenidone for at least 6 months. The GAP calculator and the GAP index were determined. The primary outcome was all-cause mortality. The prognostic accuracy of the GAP system was evaluated with respect to calibration and discrimination. Results and Conclusion: Sixty-eight IPF patients were enrolled in the study. The median follow-up was 2.4 years (range 0.1-7.4 years). A total of 22 deaths as first event (32%) and of 10 lung transplantation (15%) were recorded. The cumulative incidence of mortality at 1, 2 and 3 years was 10.4%, 22.4% and 38.4%, respectively. The differences between the predicted and observed mortality were not significant for the GAP index while the observed mortality become comparable to that predicted by the GAP calculator only in the third year of follow-up. The C-index for the GAP index was 0.74 (95% CI 0.57-0.93) while the C-statistic value for the GAP calculator was 0.77 (95% CI 0.59-0.95).
2019
- Therapeutic Strategies and Survival in Patients with Interstitial Pneumonia with Autoimmune Features
[Abstract in Rivista]
Sebastiani, M; Cassone, G; Vacchi, C; De Pasquale, L; Cerri, S; Della Casa, G; Salvarani, C; Manfredi, A
abstract
2018
- A Real-Life Multicenter National Study on Nintedanib in Severe Idiopathic Pulmonary Fibrosis
[Articolo su rivista]
Harari, Sergio; Caminati, Antonella; Poletti, Venerino; Confalonieri, Marco; Gasparini, Stefano; Lacedonia, Donato; Luppi, Fabrizio; Pesci, Alberto; Sebastiani, Alfredo; Spagnolo, Paolo; Vancheri, Carlo; Balestro, Elisabetta; Bonifazi, Martina; Cerri, Stefania; De Giacomi, Federica; Della Porta, Rossana; Foschino Barbaro, Maria Pia; Fui, Annalisa; Pasquinelli, Patrizio; Rosso, Roberta; Tomassetti, Sara; Specchia, Claudia; Rottoli, Paola
abstract
Two therapeutic options are currently available for patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. To date, there is still insufficient data on the efficacy of these 2 agents in patients with more severe disease.
2018
- Acute exacerbation of Idiopathic Pulmonary Fibrosis: lessons learned from the Acute Respiratory Distress Syndrome
[Articolo su rivista]
Marchioni, A; Tonelli, R; Ball, L; Fantini, R; Castaniere, I; Cerri, S; Luppi, F; Malerba, M; Pelosi, P; Clini, E.
abstract
Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with the Acute Respiratory Distress Syndrome (ARDS), a very severe condition commonly treated in this setting.
A review of the literature has been here conducted to underline similarities and differences for caring and managing patients with AE-IPF and ARDS.
During AE-IPF, a diffuse alveolar damage and massive loss of aeration occurs, similarly to what is observed in patients with ARDS. Differently from ARDS, no studies have concluded yet on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in these patients, as well as the precise role of other types of respiratory assistance (e.g. ECMO) or innovative therapies (e.g. polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controverial and potentially associated with increased risk of serious adverse reactions.
Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.
2018
- Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis
[Articolo su rivista]
Pancaldi, Fabrizio; Sebastiani, Marco; Cassone, Giulia; Luppi, Fabrizio; Cerri, Stefania; Della Casa, Giovanni; Manfredi, Andreina
abstract
The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the
disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis.
In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90:0%, with negative and positive predictive values of 95:0% and 83:3%; respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The
devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis.
2018
- Best supportive care for idiopathic pulmonary fibrosis: Current gaps and future directions
[Articolo su rivista]
Ferrara, Giovanni; Luppi, Fabrizio; Birring, Surinder S.; Cerri, Stefania; Caminati, Antonella; Sköld, Magnus; Kreuter, Michael
abstract
Best supportive care (BSC) is generally defined as all the interventions and the multiprofessional approach aimed to improve and optimise quality of life (QoL) in patients affected by progressive diseases. In this sense, it excludes and might be complementary to other interventions directly targeting the disease. BSC improves survival in patients with different types of cancer. Patients with idiopathic pulmonary fibrosis (IPF) experience a vast range of symptoms during the natural history of the disease and might have a beneficial effect of BSC interventions. This review highlights the current evidence on interventions targeting QoL and gaps for the clinical assessment of BSC in the treatment of IPF patients. Very few interventions to improve QoL or improve symptom control are currently supported by well-designed studies. Sound methodology is paramount in evaluating BSC in IPF, as well as the use of validated tools to measure QoL and symptom control in this specific group of patients.
2018
- Pretreatment rate of decay in forced vital capacity predicts long-term response to pirfenidone in patients with idiopathic pulmonary fibrosis.
[Articolo su rivista]
Biondini, D.; Balestro, E.; Lacedonia, D.; Cerri, S.; Milaneschi, R.; Luppi, F.; Cocconcelli, E.; Bazzan, E.; Clini, E.; Foschino, M. P.; Cosio, M. G.; Saetta, M.; Spagnolo, P.
abstract
Pirfenidone reduces functional decline and disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF). However, response to treatment is highly heterogeneous. In this study, we evaluated whether response to pirfenidone is influenced by the pre-treatment rate of forced vital capacity (FVC) decline. Fifty-seven IPF patients were categorized as rapid (RP) or slow progressors (SP) based on whether their FVC decline in the year preceding pirfenidone treatment was > or <10% predicted. Patients were followed-up every 6 months and up to 24 months following institution of pirfenidone treatment. In the entire population, pirfenidone reduced significantly the rate of FVC decline from 222 ml/yr to 68 ml/yr at 12 month (p<0.01) and 86 ml/yr at 24 month (p=0.04) follow-up. In RP, the reduction of FVC decline was evident at 6 months (706 ml/yr pre-treatment vs 35 ml/yr; p<0.01) and maintained, though to a lesser degree, at 12 (105 ml/yr; p< 0.01) and 24 months (125 ml/yr; p<0.02). Conversely, among SP the reduction in FVC decline was not significant at any of the time points analyzed. Pirfenidone reduces significantly the rate of FVC decline in patients with IPF. However, the beneficial effect is more pronounced and long-lasting in patients with rapidly progressive disease.
2018
- Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist
[Articolo su rivista]
Sverzellati, Nicola; Odone, Anna; Silva, Mario; Polverosi, Roberta; Florio, Carlo; Cardinale, Luciano; Cortese, Giancarlo; Addonisio, Giancarlo; Zompatori, Maurizio; Dalpiaz, Giorgia; Piciucchi, Sara; Larici, Anna Rita; Agostini, Carlo; Albera, Carlo; Attinà, Domenico; Battista, Giuseppe; Bertelli, Elena; Giuseppina, Bertorelli; Bnà, Claudio; Bonifazi, Martina; Bonomo, Lorenzo; Borghesi, Andrea; Calandriello, Lucio; Caminati, Antonella; Capannelli, Diana; Cerri, Stefania; Ciccarese, Federica; Colombi, Davide; Confalonieri, Marco; Del Ciello, Annaemilia; della Casa, Giovanni; Dore, Roberto; Falaschi, Fabio; Farchione, Alessandra; Feragalli, Beatrice; Franchi, Paola; Gavelli, Giampaolo; Harari, Sergio; Luppi, Fabrizio; Maggi, Fabio; Mazzei, Maria Antonietta; Mereu, Manuela; Milanese, Gianluca; Palmucci, Stefano; Patea, Rosa Lucia; Pesci, Alberto; Piolanti, Marco; Poletti, Venerino; Rea, Gaetano; Richeldi, Luca; Rogliani, Paola; Romei, Chiara; Rottoli, Paola; Sanduzzi-Zamparelli, Alessandro; Sebastiani, Alfredo; Sergiacomi, Gianluigi; Soardi, Gian Alberto; Spaggiari, Lucia; Spagnolo, Paolo; Tomassetti, Sara; Trisolini, Rocco; Valentini, Adele; Vancheri, Carlo; Vespro, Valentina; Volterrani, Luca
abstract
Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteriaâthe Delphi itemsâfor rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as âessentialâ, âoptionalâ, or ânot relevantâ. The items rated âessentialâ by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated âessentialâ by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated âessentialâ by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists.
2018
- The encaged lung: rapidly progressive idiopathic pleurisy.
[Articolo su rivista]
Castaniere, I; Tonelli, R; Fantini, R; Marchioni, A; Garofalo, M; Clini, E; Cerri, S.
abstract
Here we present a case of an idiopathic fibrinous pleurisy affecting a 56-year old non-smoker male that has shown a rapidly progressive course. With a brief review of the literature we discuss the absence of any identified cause of pleurisy as a relatively common condition, requiring attention and clinical awareness.
2018
- Ultrasound assessed Diaphragm Impairment is a Predictor of Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease undergoing Non-Invasive Ventilation.
[Articolo su rivista]
Marchioni, Alessandro; Castaniere, Ivana; Tonelli, Roberto; Fantini, Riccardo; Fontana, Matteo; Luca, Tabbi; Andrea, Viani; Francesco, Giaroni; Ruggieri, Valentina; Cerri, Stefania; Clini, Enrico
abstract
Background. Ultrasound (US) evaluation of diaphragm dysfunction (DD) has proved to be a reliable technique in critical care. In this single center prospective study we investigated the impact of US assessed DD on Non Invasive Ventilation (NIV) failure in AECOPD patients and its correlation with the trans-diaphragmatic pressure assessed through invasive sniff maneuver (Pdi sniff).
Methods. A population of 75 consecutive AECOPD with hypercapnic acidosis admitted in our Respiratory Intensive Care Unit (RICU) were enrolled. Change of the diaphragm thickness (ΔTdi) < 20% during tidal volume was the pre-definite cut off to identify DD+/-. Correlations between ΔTdi <20% NIV failure and other clinical outcomes was investigated. Correlation between ΔTdi and Pdi sniff values was analyzed in a subset of 10 patients.
Results. DD+ had higher risk for NIV failure as compared with DD- (RR= 4.4, p<0.001) and was significantly associated with greater RICU, in-hospital and 90-day mortality rate, MV duration, tracheostomy rate, and RICU stay. A huge increase in NIV failure (HR=6.2, p< 0.0001) and 90-day mortality (HR=4.7, p=0.008) in DD+ was reported at the Kaplan-Meyer analysis. ΔTdi highly correlated with Pdi sniff (r Pearson = 0.81, p= 0.004). ΔTdi< 20% showed better accuracy in predicting NIV failure when compared to baseline pH value and early change of both arterial blood pH and pCO2 following NIV start (AUC=0.84, 0.51, 0.56, 0.54 respectively, p<0.0001).
Conclusion. Early and non-invasive US assessment of DD during severe AECOPD is reliable and accurate in identifying patients at major risk for NIV failure and worse prognosis.
2018
- "Velcro-type" crackles predict specific radiologic features of fibrotic interstitial lung disease
[Articolo su rivista]
Sgalla, Giacomo; Walsh, Simon L. F.; Sverzellati, Nicola; Fletcher, Sophie; Cerri, Stefania; Dimitrov, Borislav; Nikolic, Dragana; Barney, Anna; Pancaldi, Fabrizio; Larcher, Luca; Luppi, Fabrizio; Jones, Mark G.; Davies, Donna; Richeldi, Luca
abstract
Background: "Velcro-type" crackles on chest auscultation are considered a typical acoustic finding of Fibrotic Interstitial Lung Disease (FILD), however whether they may have a role in the early detection of these disorders has been unknown. This study investigated how "Velcro-type" crackles correlate with the presence of distinct patterns of FILD and individual radiologic features of pulmonary fibrosis on High Resolution Computed Tomography (HRCT). Methods: Lung sounds were digitally recorded from subjects immediately prior to undergoing clinically indicated chest HRCT. Audio files were independently assessed by two chest physicians and both full volume and single HRCT sections corresponding to the recording sites were extracted. The relationships between audible "Velcro-type" crackles and radiologic HRCT patterns and individual features of pulmonary fibrosis were investigated using multivariate regression models. Results: 148 subjects were enrolled: bilateral "Velcro-type" crackles predicted the presence of FILD at HRCT (OR 13.46, 95% CI 5.85-30.96, p < 0.001) and most strongly the Usual Interstitial Pneumonia (UIP) pattern (OR 19.8, 95% CI 5.28-74.25, p < 0.001). Extent of isolated reticulation (OR 2.04, 95% CI 1.62-2.57, p < 0.001), honeycombing (OR 1.88, 95% CI 1.24-2.83, < 0.01), ground glass opacities (OR 1.74, 95% CI 1.29-2.32, p < 0.001) and traction bronchiectasis (OR 1.55, 95% CI 1.03-2.32, p < 0.05) were all independently associated with the presence of "Velcro-type" crackles. Conclusions: "Velcro-type" crackles predict the presence of FILD and directly correlate with the extent of distinct radiologic features of pulmonary fibrosis. Such evidence provides grounds for further investigation of lung sounds as an early identification tool in FILD.
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: Prevalence and characterization of non-sicca onset primary Sjögren syndrome with interstitial lung involvement (Clinical Rheumatology, (2017), 36, 6, (1261-1268), 10.1007/s10067-017-3601-1)
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cerri, S.; Cassone, G.; Bellini, P.; Della Casa, G.; Luppi, F.; Ferri, C.
abstract
This article originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above. The original article was corrected.
2017
- Interstitial lung disease is associated to infections of lower respiratory tract in immunocompromised rheumatoid arthritis patients
[Articolo su rivista]
Sebastiani, Marco; Manfredi, Andreina Teresa; Cassone, Giulia; Sandri, Gilda; Cerri, Stefania; Ferri, Clodoveo
abstract
Immunosuppressive treatment increase the risk of lower respiratory tract infections particularly in RA-ILD
patients, suggesting a more careful surveillance in this subgroup of patients
2017
- Malattie infiltrative diffuse del polmone
[Capitolo/Saggio]
Albera, Carlo; Cerri, Stefania; Luppi, Fabrizio; Richeldi, Luca; Rogliani, Paola; Spagnolo, Paolo
abstract
Le pneumopatie infiltative diffuse (PID) o interstiziopatie polmonari rappresentano un ampio ed eterogeneo gruppo di patologie, alcune a esclusivo interessamento polmonare, altre in cui il polmone è solo uno degli organi colpiti. Le PID possono insorgere in modo acuto, subacuto o cronico, o avere un decorso subclinico e indolente. Inoltre, mentre alcune di esse possono regredire (con o senza terapia), altre, quali la fibrosi polmonare idiopatica, progrediscono in modo inesorabile, anche se alcuni farmaci ad azione antifibrotica sono in grado di rallentarne la progressione.
2017
- Management of Idiopathic Pulmonary Fibrosis
[Capitolo/Saggio]
Cerri, Stefania; Spagnolo, Paolo; Luppi, Fabrizio; Sgalla, Giacomo; Richeldi, Luca
abstract
Idiopathic pulmonary fibrosis (IPF) is one of the most challenging diseases for chest physicians for a number of reasons, including the complexity of the diagnostic process, which requires close interaction with different specialists, and the almost invariably poor prognosis, with a 5-year survival of ∼20%. Moreover, until recently, IPF has lacked effective therapies. Following two decades of clinical trials, most of which have produced negative results, pirfenidone, a compound with broad antifibrotic, antiinflammatory, and antioxidant properties, and nintedanib, an orally available, small molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors, have proved equally effective in slowing down functional decline and disease progression
with an acceptable safety profile. However, neither pirfenidone nor nintedanib is a cure for IPF;neither drug improves lung function and the disease continues to progress in most patients despite treatment. Likewise, the modalities for the follow-up of IPF patients are poorly defined. Accordingly, all decisions related to patient management need to be extensively
discussed and agreed upon with the patients and their families. As a result, few respiratory disorders require ofchest physicians more interactive skills and more dedication than IPF.
2017
- NEW PERSPECTIVES IN DIAGNOSIS OF INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. VALIDATION STUDY OF AN ELECTRONIC STETHOSCOPE AND AD HOC SOFTWARE FOR DETECTION OF PULMONARY CRACKLES
[Abstract in Rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cassone, Giulia; Fedele, A. L.; Venerito, V.; Trevisani, M.; Furini, F.; Addimanda, O.; Gremese, E.; Iannone, F.; DELLA CASA, Giovanni; Cerri, Stefania; Sandri, Gilda; Pancaldi, Fabrizio; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint swelling and tenderness, secondary to the immune-system dysfunction, often complicated by extra-articular manifestations. Among them, lung involvement is very frequent and interstitial lung disease (ILD) represents one of the deleterious complications of RA with impact on both therapeutic approach and overall prognosis. Nevertheless, diagnosis of ILD often remains missing or delayed.
Objectives: To preliminarily evaluate the predictive value of pulmonary sound recorded by an electronic stethoscope (ES) and elaborated by an ad hoc software in identification of RA-ILD diagnosed by mean of high resolution computed tomography (HRCT) in a multicenter study.
Methods: RA patients who underwent HRCT in the last 12 months were enrolled. They were all auscultated with the ES (Littmann 3200TM 3M, USA), bilaterally, at dorsal level, in at least 3 pulmonary fields (medium and basal). All tracks recorded were analyzed by a suitably developed software capable of recognizing pathological crackles in lung sounds. Results were compared with radiologic findings detected in a blind manner by an expert radiologist.
Results: One hundred and six RA patients were enrolled (M/F: 1/2.5, mean age 68.7±10.3); among them 45 (42.5%) showed ILD at HRCT. Three patients were excluded because of a low quality of the sound recorded. The algorithm showed a sensitivity and specificity of 72.1% and 84.4%, respectively and a positive/negative predictive value of 69.1% and 86.3%, respectively.
Conclusions: Despite preliminary, these data suggest an important role of ES in clinical practice for an early diagnosis of ILD in RA patients and a significant reduction of inappropriate prescription of HRCT. Since very different types of ILD can occur in course of RA, with different radiologic features and localization, proper development of the measurement setup (ES and ad hoc software for the detection of PC) could further increase its predictive value, in particular to avoid incorrect records and misdiagnosis. The routinely employment of ES and proper software, combined to clinical findings (cough, dyspnea) and respiratory lung function, could increase our ability to early identify ILD in RA patients.
2017
- Pneumologia
[Capitolo/Saggio]
Clini, Enrico; Beghe', Bianca; Cerri, Stefania; Fabbri, L. E. O. N. A. R. D. O.
abstract
Non disponibile
2017
- Prevalence and characterization of non-sicca onset primary Sjögren syndrome with interstitial lung involvement
[Articolo su rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cerri, Stefania; Cassone, Giulia; Bellini, Pierantonio; DELLA CASA, Giovanni; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10–20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48 months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren’s syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.
2017
- The performance of the GAP model in patients with rheumatoid arthritis associated interstitial lung disease
[Articolo su rivista]
Morisset, Julie; Vittinghoff, Eric; Lee, Bo Young; Tonelli, Roberto; Hu, Xiaowen; Elicker, Brett M.; Ryu, Jay H.; Jones, Kirk D.; Cerri, Stefania; Manfredi, Andreina Teresa; Sebastiani, Marco; Gross, Andrew J.; Ley, Brett; Wolters, Paul J.; King, Talmadge E.; Kim, Dong Soon; Collard, Harold R.; Lee, JOYCE SUJIN
abstract
Background Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Similarities have been observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP (usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology) model has been shown to predict mortality in patients with IPF, but its ability to predict mortality in RA-ILD is not known. Methods We identified 309 patients with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients with ILD. The primary endpoint was mortality. To handle missing data (n = 219 subjects with complete dataset), multiple imputation by iterative chained equations was used. Using the GAP model as a baseline, we assessed improvements in mortality risk prediction achieved by incorporating additional variables. Model discrimination was assessed using the c-index, and calibration was checked by comparing observed and expected incidence of death. Results Patients had a mean age of 65 years and were predominantly female (54%). The mean forced vital capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon monoxide (DLCO) % predicted was 55. Twenty-four percent of the 236 patients with a high-resolution computed tomography scan available for review had a definite UIP pattern. The original GAP model, including gender, age, FVC%, and DLCO%, had a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at 1, 2 and 3 years. Model discrimination was not meaningfully improved by adding other clinical variables. Conclusion The GAP model that was derived for IPF performs similarly as a mortality risk prediction tool in RA-ILD.
2017
- Tubercolosi
[Capitolo/Saggio]
Cerri, Stefania; Richeldi, Luca; Roversi, Pietro
abstract
L'infezione da micobatteri tubercolari ha accompagnato la storia dell'uomo sin dall'antichità. Nei secoli la malattia tubercolare ha rappresentato una piaga sociale, principale responsabile di morbilità e mortalità nella popolazione giovane adulta, e ancora oggi è tra le prime 10 cause di morte al mondo con circa 1,8 milioni di decessi all'anno.
2016
- Etiology and Level of Lung Derangement Do Not Affect the Beneficial Effect of Pulmonary Rehabilitation in Patients with Interstitial Lung Diseases
[Abstract in Rivista]
Tonelli, Roberto; Lanini, Barbara; Romagnoli, Isabella; Presi, Ilenia; Cocconcelli, Elisabetta; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Gigliotti, Francesco; Clini, Enrico
abstract
A growing body of literature suggests that comprehensive Pulmonary Rehabilitation (PR) improves symptoms and functional capacity also in patients with Interstitial Lung Disease. Aim of this study was to investigate whether the baseline level of functional capacity or lung derangement, and ILD etiology may predict and affect outcomes’ response to PR in these patients.
MATERIALS AND METHODS
Patients with ILD of different etiology were referred and prospectively admitted to PR, delivered according to a standardized protocol. Spirometry, Diffuse Lung Capacity for Carbon Monoxide [DLCO], incremental cyclo-ergometry test, Six Minutes Walking Distance Test [6MWDT], questionnaires on dyspnea and quality of life (St. George Respiratory Questionnaire-SGRQ, 5-point Medical Research Council scale-MRC) were assessed pre- and post- rehabilitation course; change from baseline of any measured variables was considered to assess the impact of PR on functional capacity, perceived symptoms and quality of life, respectively. Patients were stratified according to their level of DLCO, Forced Vital Capacity (FVC), 6MWTD, etiology (IPF or non-IPF), and GAP index (in IPF patients only). Analyses of changes from baseline and correlation test were conducted as appropriate.
RESULTS
Thirty-nine patients (mean age 66.87 ± 10.9 ys, IPF 62.5%) were enrolled and completed the PR course. 6MWDT (+54.3m, 95%CI 34.9-73.7, p < .0001), cycling time (+ 70.0%, p = .0009) and power (+60.4%, p= .008), iso-time dyspnea (-33.1%, p < .0001) and limb fatigue (-40.8%, p < .0001), SGRQ, MRC (p < .0001) significantly improved over time. Patients with lower baseline 6MWD showed greater change in 6MWD (Pearson r score = - .359, p = .034) and symptoms relief at SGRQ (r = -.229, p = .038). Different levels of FVC, DLCO, GAP index and etiology did not correlate with functional and symptoms outcomes.
CONCLUSION
Present study confirms that comprehensive rehabilitation is effective in patients with ILDs of different severity, and etiology and that baseline walking capacity inversely correlates with functional and symptom changes. Lung derangement or etiology does not affect outcomes following rehabilitation.
2016
- INTERSTITIAL LUNG DISEASE IS ASSOCIATED TO INFECTIONS OF LOWER RESPIRATORY TRACT IN IMMUNOCOMPROMISED RHEUMATOID ARTHRITIS PATIENTS
[Abstract in Rivista]
Cassone, Giulia; Sebastiani, Marco; Manfredi, Andreina Teresa; Campomori, Federica; Spinella, Amelia; Sandri, Gilda; Luppi, Fabrizio; Cerri, Stefania; Ferri, Clodoveo
abstract
Objectives. To investigate the possible association between demographic, serological and clinical features of rheumatoid arthritis (RA) and the lower respiratory tract (LRT) infections.
We further analyzed the possible relationships between demographic, serological and clinical features and LRT infections in a sub-group of patients with RA-associated interstitial lung disease (ILD).
Materials and Methods. Demographic, serological, clinical and therapeutic features of 563 RA patients were retrospectively analyzed (female/male ratio 3.43, mean age 64.8±13.6SD years, mean disease duration 11.5±9.4SD years).
Results. During a mean follow-up of 138.9±131.3SD months, we observed 47 patients with at least one episode of LRT infection.The presence of RA-associated ILD, therapy with steroids, and b-DMARDs were significantly associated to LRT infections (p=0.016, p=0.000, and p=0.01 for ILD, steroids and b-DMARDs, respectively).
All variables remained independently associated to infections of LRT also at logistic regression analysis; while no differences were observed with regard to the kind of the b-DMARDs, namely anti-tumor necrosis factors alpha inhibitors, rituximab, abatacept, tocilizumab. Moreover, the presence of ILD was associated to more severe LRT infectious
complications, requiring hospitalization in 55.6% of patients, compared to 27.8% of patients without ILD (p=0.042). Since patients with ILD showed a risk to develop an infection of LRT 4.5 times higher of patients without ILD, we further analyzed this peculiar sub-group of patients. Among 33/563 (5.9%) patients with ILD (female/male ratio 2/1, mean age 71.8±10.6 years, mean disease duration 16.1±13.0 years), only b-DMARDs were associated to infections of LRT (p=0.002). Of interest, a combination therapy with b-DMARDs, methotrexate, and corticosteroids was significantly more
frequently recorded in RA-ILD patients compared to those without LRT infections (81.8% vs 13.6% of patients; p=0.001).
Conclusions. ILD is an important extra-articular complication of RA, involving about 5-10% of patients, and its current therapeutic approach is still under debate, because the lack of evidences that immunosuppressants are effective both on joint and lung involvement. Idiopathic pulmonary fibrosis (IPF) is usually compared to RA-ILD for their similarity in radiological and histological features. In IPF patients, the PANTHER-IPF study showed an excess mortality due to pulmonary infection in azathioprine and prednisone treatment arm, and corticosteroids increase the risk of serious infection fourfold. Our data confirm, with the limit of a low number of patients analyzed, that immunosuppressive treatment increase the risk of LRT infections particularly in RA-ILD patients, suggesting a more careful surveillance in this sub-group of patients.
In conclusion, in patients with RA-ILD, it is necessary to balance the control of joint inflammation with the risk of drug-related LRT infections; this latter could be significantly reduced by tailoring both drug combination and doses (corticosteroids, traditional, and b-DMARDs) on individual patients.
2016
- Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease: Our interdisciplinary rheumatology-pneumology experience, and review of the literature
[Articolo su rivista]
Ferri, Clodoveo; Manfredi, Andreina; Sebastiani, Marco; Colaci, Michele; Giuggioli, Dilia; Vacchi, Caterina; Della Casa, Giovanni; Cerri, Stefania; Torricelli, Pietro; Luppi, Fabrizio
abstract
Background: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lungs, varying from idiopathic interstitial pneumonias to secondary variants, including the ILDs associated to connective tissue diseases (CTDs). In addition, a number of patients are recognized as unclassifiable ILD (U-ILD), because of the inability to reach a definite diagnosis; some of them show autoimmune manifestations not fulfilling the classification criteria of a given CTD. The term interstitial pneumonia with autoimmune features (IPAF) has been recently proposed for this particular ILD subset. Methods: Here, we report our experience resulting from the integrated - pneumology/rheumatology - approach to patients with suspected ILDs or CTDs referred to our university-based Center for the Rare Pulmonary Diseases and Rheumatology Unit, from January 2009 to June 2015, with particular attention to the above-mentioned U-ILD, IPAF, and undifferentiated connective tissue disease (UCTD). The comparative analysis of these clinical variants was carried out; moreover, the observed findings were compared with the results of the updated review of the literature. Results: After the first clinical assessment, the U-ILD were identified in 50 patients; afterwards, on the basis of clinico-serological and radiological findings U-ILD group was subdivided into 2 subgroups, namely U-ILD without any clinical extra-thoracic manifestations and/or immunological alterations (15 pts) and IPAF according to the above-mentioned classification criteria (35 pts). Patients with either IPAF or U-ILD were compared with a series of 52 stable UCTD (disease duration ≥. 3. years), followed at our Rheumatology Unit. Some important differences were evidenced among the 3 series of U-ILD, IPAF, and UCTD: firstly, female gender was more frequent in patients with UCTD (86%) or IPAF (69%) compared with U-ILD (60%) or idiopathic pulmonary fibrosis (24%; p = 0.001). In addition, UCTD patients were younger and showed longer disease duration. More interestingly, both UCTD and IPAF series show a comparable prevalence of various clinical manifestations, with the exception of the interstitial lung involvement detectable in a very small percentage of UCTD patients.Concordantly, the review of the literature evidenced two main subsets of U-ILD, one is characterized by isolated unclassifiable interstitial pneumonia and another one composed by subjects with clinically prevalent lung involvement in the setting of not definite CTD, the recently proposed IPAF. Conclusion: We hypothesize that IPAF and UCTD might represent two clinical variants of the same systemic autoimmune disorders. The marked difference regarding the prevalence of ILD, which is the clinical hallmark of IPAF but very rare in UCTD, may at least in part reflect a selection bias of patients generally referred to different specialist centers, i.e. pneumology or rheumatology, according to the presence/absence of clinically dominant ILD, respectively. Well-integrated, interdisciplinary teams are recommended for the assessment and management of these patients in the clinical practice. Finally, the cooperation between multidisciplinary groups with different experiences may be advisable for a validation study of the proposed nomenclature and classification criteria of these indefinable ILD/CTD variants.
2016
- Multidrug-resistant tuberculosis outbreak in an Italian prison: Tolerance of pyrazinamide plus levofloxacin prophylaxis and serial interferon gamma release assays
[Articolo su rivista]
Bedini, Andrea; Garlassi, Elisa; Stentarelli, Chiara; Petrella, S.; Meacci, M.; Meccugni, B.; Meschiari, Marianna; Franceschini, Elisa; Cerri, Stefania; Brasacchio, A.; Rumpianesi, F.; Richeldi, Luca; Mussini, Cristina
abstract
The optimal treatment for latent tuberculosis infection (LTBI) in subjects exposed to multidrug-resistant (MDR) tuberculosis (TB) remains unclear, and the change in response of the QuantiFERON-TB Gold In-Tube (QTB-IT) test during and after treatment is unknown. Between May 2010 and August 2010, 39 prisoners at the 'Casa Circondariale' of Modena, Italy, were exposed to a patient with active pulmonary MDR TB. All contacts were tested with the tuberculin skin test and QTB-IT. Upon exclusion of active TB, subjects positive to both tests were offered 6 months' treatment with pyrazinamide (PZA) and levofloxacin (LVX). QTB-IT testing was repeated at 3 and 6 months after initial testing in all subjects who were offered LTBI treatment. Seventeen (43.5%) of 39 subjects tested positive to both tuberculin skin test and QTB-IT test, and 12 (70.5%) agreed to receive therapy with PZA and LVX at standard doses. Only five (41.6%) of 12 subjects completed 6 months' treatment. Reasons for discontinuation were asymptomatic hepatitis, gastritis and diarrhoea. The QTB-IT values decreased in all subjects who completed the treatment, in two (33%) of six of those who received treatment for less than 3 months and in one (50%) of two patients who discontinued therapy after 3 months. The QTB-IT test results never turned negative. Despite the small number of subjects, the study confirmed that PZA plus LVX is a poorly tolerated option for MDR LTBI treatment. We observed a large degree of variation in the results of the QTB-IT test results among participants. The study confirmed that the interferon gamma release assay is not a reliable tool for monitoring the treatment of MDR LTBI in clinical practice.
2016
- Occurrence of idiopathic pulmonary fibrosis during immunosuppressive treatment: a case report
[Articolo su rivista]
Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca; Luppi, Fabrizio
abstract
Immunosuppressive therapy has been-until the recent release of new guidelines on diagnosis and management-the recommended treatment for idiopathic pulmonary fibrosis. However, its efficacy in patients with idiopathic pulmonary fibrosis has always been a matter of debate.
2016
- Predicting Mortality in Patients with Rheumatoid Arthritis Related Interstitial Lung Disease: Expanding The GAP Model
[Abstract in Rivista]
Morisset, Julie; Vittinghoff, Eric; Lee, Bo Young; Tonelli, Tonelli; Hu, Xiaowen; Elicker, Brett M; Ryu, Jay H; Jones, Kirk D; Cerri, Stefania; Manfredi, Andreina Teresa; Sebastiani, Marco; Ley, Brett J; Wolters, Paul J; King, Talmadge E; Kim, Dong Soon; Collard, Harold R; Lee, JOYCE SUJIN
abstract
Rationale: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a disease associated with morbidity and mortality. There is a high prevalence of usual interstitial pneumonia (UIP) pattern in RA-ILD and similarities have been observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP form of RA-ILD. The GAP (gender, age, physiology) model has been shown to predict mortality in patients with IPF, but its ability to predict mortality in RA-ILD is not known.
Methods: We identified 309 patients with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients with ILD (Mayo Clinic, University of Ulsan, University of California, San Francisco and University of Modena & Reggio Emilia). The primary endpoint was mortality. To handle the issue of missing data, multiple imputation by iterative chained equations was used, resulting in 20 completed datasets. Linear and logistic imputation models were used for continuous and binary covariates, respectively. Using the GAP model as the
baseline mortality prediction model, we determined the additive model performance for mortality risk prediction by incorporating additional variables. Model discrimination was assessed using the c-index.
Results: Patients had a mean age of 65 years and were predominantly female (54%). The mean forced vital capacity % predicted was 73 and the mean diffusing capacity for carbon monoxide (DLCO) % predicted was 55. The majority of patients had positive rheumatoid factor (RF) (89%) or positive anti-cyclic citrullinated peptide antibody (71%). Twenty-four percent of patients had a definite UIP pattern on high-resolution computed tomography (HRCT). The original GAP model (Gender, Age, FVC%, DLCO%) had a c-index of 0.69 in our cohort. The performance of this model improved by expanding the GAP model to include 2 additional variables: definite UIP pattern on HRCT and positive RF. The c-index of this expanded model was 0.71.
Conclusions: The addition of 2 variables, definite UIP pattern on HRCT and RF, improves the performance of the GAP model to predict mortality in patients with RA-ILD.
2016
- Pulmonary Carcinosarcoma Arising in the Framework of an Idiopathic Pulmonary Fibrosis
[Articolo su rivista]
Lococo, Filippo; Luppi, Fabrizio; Cerri, Stefania; Montanari, Gloria; Stefani, Alessandro; Rossi, Giulio
abstract
Si descrive un raro caso di paziente con fibrosi polmonare idiopatica nell'ambito della quale è insorto in carcinosarcoma polmonare. Il paziente è stato operato con intento radicale ma ha presentato una riacutizzazione della fibrosi polmonare nel postoperatorio. Trattato farmacologicamente e con supporto ventilatorio è progressivamente migliorato fino a venire dimesso in buone condizioni.
2016
- Radiologic classification of usual interstitial pneumonia in rheumatoid arthritis-related interstitial lung disease: correlations with clinical, serological and demographic features of disease
[Articolo su rivista]
Sebastiani, Marco; Manfredi, Andreina Teresa; Cerri, Stefania; Della Casa, Giovanni; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) and usual interstitial pneumonia (UIP) is considered the most frequent histo-pathological pattern of RA-ILD; high-resolution computed tomography (HRCT) is crucial for the evaluation of ILD patterns without recourse to lung biopsy.
In 2011, the ATS/ERS/JRS/ALAT statement for diagnosis and management of idiopathic pulmonary fibrosis (IPF) provided consensus guidelines to identify a definite, possible or inconsistent with UIP pattern on HRCT, based on radiological features; previous studies suggest that the above classification should also be appropriate for RA-ILD.
We retrospectively identified 97 unselected RA patients, classified according to 2010 ACR/EULAR classification criteria, referred to our Rheumatology Unit from October 2004 to March 2013, with at least one chest HRCT, regardless of its indication.
Demographic, clinical, serological data, and drugs administered before HRCT were collected for all patients (table 1). RA-ILD diagnosis was conventionally identified with HRCT.
A thoracic radiologist experienced in interstitial lung disease scored all HRCT images, classifying them as definite, possible or inconsistent with UIP.
Among 97 RA patients, 32 showed RA-ILD (15 with definite or possible UIP pattern and 17 with an inconsistent with UIP pattern), while the 65 patients without ILD were used as control group.
With the exception of dyspnea, no differences were observed comparing patients with or without ILD. According to radiological classification, we also compared patients with a definite or possible UIP pattern (UIP group), patients with a pattern inconsistent with UIP (non UIP group), and controls.
No differences were observed comparing anti-CCP, rheumatoid factor, and ANA positivity, while ENA were more frequent in the UIP group, compared to the controls (p=0.039). Anti-Jo1 and anti-SSA were the prevalent specificities of ENA, without differences between the groups (only 1 patient fullfilled also criteria for Sjogren’s syndrome).
All patients with UIP pattern had more than 63 years at the time of HRCT, and they were more frequently males and smokers (table 1).
The occurrence of UIP pattern increased according to the number of significantly associated features (namely, male gender, smoking habit, presence of ENA, and age higher than 63 years). In fact, patients with UIP pattern showed the co-presence of 3 or 4 factors in 61% of cases, compared with no cases in non UIP group and 13.6% in control group (p<.001 and p=.001, respectively).
Since IPF showed similar associations (particularly with male gender, elderly and smoke), it would be interesting a future speculation on potential pathogenic and therapeutic overlap between the two diseases. On the other side, the presence of anti-ENA in UIP pattern could only theoretically suggest partial overlap with connective tissue disease in RA-ILD, with possible prognostic and therapeutic implications. Published data have not clarified the association with anti-CCP and rheumatoid factor.
The link between RA-ILD and drugs is still uncertain. The poor quality of published data and the lack of randomized controlled trials contribute to confounding information in clinical practice.
HRCT could improve diagnosis and classification of ILD in RA patients, reserving lung biopsy only for selected cases. Moreover, at present, definition and classification of RA-ILD are still under debate, and the use of classifications based on radiological findings could improve the identification of more homogeneous groups of patients with different lung involvement. Interestingly, our study highlights the peculiarities of UIP pattern, showing different clinical associations from the ones of the whole ILD group.
Since ILD can significantly affect the survival, a careful follow-up for ILD is mandatory in all RA patients and a mult
2016
- Validation of a Method for Automatic Detection of Lung Sounds in Fibrotic Interstitial Lung Disease
[Abstract in Rivista]
Sgalla, Giacomo; Nikolic, Dragana; Walsh, Simon L; Fletcher, Sophie; Cerri, Stefania; Luppi, Fabrizio; Jones, Mark G; Davies, Donna E; Sverzellati, Nicola; Hansell, DAVID MATTHEW; Barney, Anna; Richeldi, Luca
abstract
BACKGROUND
Delayed diagnosis of fibrotic interstitial lung disease (ILD) is characterized by significant repercussions for management and survival. A timely assessment of “velcro-type” crackles at lung auscultation might prompt a proper diagnostic process in these patients. The accuracy of objective, computerized methods in detecting ILD from respiratory sounds has not been systematically assessed in a clinical setting. We aimed to validate automatic detection of “velcro-type” crackles by comparing the results of lung sounds analysis with chest high
resolution computed tomography (HRCT) scans.
METHODS
Lung sounds were recorded using an electronic stethoscope (Littmann 3200) from anatomically defined sites in 56 subjects (derivation cohort) undergoing a chest HRCT scan in Modena (Italy). Three-hundred anonymized, single-layer HRCT images corresponding to the sites of sound recording were reviewed by two radiologists with expertise in ILD and scored for the signs indicating lung fibrosis. All audio recordings were analyzed by extracting a set of global acoustic features from each file and different classification algorithms were employed on a subset of the best ranked features to classify the data into two groups. The gold standard used to label the ground truth for each sound file was based on the evidence of fibrosis in the corresponding HRCT image. Two ILD physicians were also asked to independently assess the sound files for the presence of “velcro-type” crackles. The results were validated in a further cohort of 59 patients (validation cohort) undergoing chest HRCT in Parma (Italy). Three-hundred nineteen HRCT images and corresponding sound files were obtained.
RESULTS
In the derivation cohort, accuracy of 74.4% was achieved in automatic detection of lung sounds associated with fibrotic HRCT images. However, although specificity was high (87.3%), sensitivity was lower (48.5%). The two respiratory physicians showed comparable performance, with accuracy 71.6%, specificity 82.3% and sensitivity 49.9%. The results of the automated detection were substantially reproduced in the validation cohort (accuracy 70.2%, specificity 84.7%, sensitivity 45.8%).
CONCLUSION
An automated method can identify lung sounds associated with pulmonary fibrosis at HRCT, and replicates the performance of experienced clinicians on the same data set. This suggests that there are substantial grounds for developing an automated method for clinical detection of fibrotic ILD.
2015
- Acute exacerbation of idiopathic pulmonary fibrosis: a clinical review
[Articolo su rivista]
Luppi, Fabrizio; Cerri, Stefania; Taddei, Sofia; Ferrara, Giovanni; Cottin, Vincent
abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic disease limited to the lung, with high variability in the course of disease from one patient to another. Patients with IPF may experience acute respiratory deteriorations; many of these acute declines are idiopathic and are termed acute exacerbations (AE) of IPF. In these cases, the exclusion of alternative causes of rapid deterioration, including heart failure, bilateral pneumonia or pulmonary embolism, is a challenging goal. AE may occur at any time during the course of IPF, although they are more common in patients with more progressive disease and gastroesophageal reflux. Surgical lung biopsy or even surgical procedures in organs other than the lungs may also trigger AE, mainly in rapidly progressive or advanced IPF. Current diagnostic criteria include the presence of new-onset ground glass opacities or airspace consolidation superimposed on an underlying usual interstitial pneumonia pattern seen on high-resolution computed tomography. The outcome is poor with a short-term mortality in excess of 50 % despite therapy. Currently, there is no treatment with demonstrated efficacy for AE-IPF: empirical high-dose corticosteroid therapy is generally used, with or without immunosuppressive agents, with limited evidence. On the other hand, there is hope that new treatments to slow down progression of IPF will translate into a reduction of AE-IPF’s occurrence. In conclusion, although significant progress in assessing disease severity in IPF has been made, AEs remain unpredictable and are associated with a high risk of death. Improvements in our understanding of the etiology, risk factors, clinical predictors and epidemiology are needed. It is the goal of clinical researchers in the field to provide respiratory physicians with evidence-based guidance to identify patients who may benefit from therapy for preventing or treating AE-IPF.
2015
- Challenges in idiopathic interstitial lung disease
[Articolo su rivista]
Luppi, Fabrizio; Cerri, Stefania; Sgalla, Giacomo; Richeldi, Luca
abstract
Idiopathic interstitial pneumonias (IIPs) are a group of pulmonary disorders with distinct histologic and radiologic appearances and no identiiable cause. The new classiication of IIPs published in 2013 distinguishes six distinct major entities, including chronic, usually progressive ibrosing diseases, such as idiopathic pulmonary ibrosis (IPF) and idiopathic nonspeciic interstitial pneumonia. IPF, an invariably progressive and ultimately fatal lung disease that occurs in older adults, is the most frequent among the IIPs. Recent evidence and international guidelines advocate the importance of chest high-resolution computed tomography and multidisciplinary discussion (MDD) in the initial diagnostic assessment of patients with suspected IPF. MDD is currently considered the gold standard because improves the accuracy of IIPs diagnosis, avoiding unnecessary testing, and optimizing patient management, particularly nowadays that two drugs have been approved by regulatory agencies for the treatment of IPF. In this review, we focus on the revised diagnostic criteria for IIPs and IPF and provide an overview of the most recent clinical trials. Finally, we stress the fact that NSIP, one of the most frequent differential diagnosis in cases presenting with suspected IPF, is not anymore considered a provisional entity, but a deinite clinical-pathological entity.
2015
- Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study
[Articolo su rivista]
Harari, S.; Caminati, A.; Albera, C.; Vancheri, C.; Poletti, V.; Pesci, A.; Luppi, F.; Saltini, C.; Agostini, C.; Bargagli, E.; Sebastiani, A.; Sanduzzi, A.; Giunta, V.; Della Porta, R.; Bandelli, G. P.; Puglisi, S.; Tomassetti, S.; Biffi, A.; Cerri, S.; Mari, A.; Cinetto, F.; Tirelli, F.; Farinelli, G.; Bocchino, M.; Specchia, C.; Confalonieri, M.
abstract
Background In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. Methods We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. Results At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and â¤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. Conclusions In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.
2015
- Infezioni sistemiche a prevalente localizzazione polmonare
[Capitolo/Saggio]
Cerri, Stefania; Ferrara, Giovanni; Roversi, Pietro; Pardi, Ruggero; Richeldi, Luca
abstract
Il capitolo è dedicato alla trattazione dell'infezione da micobatteri tubercolari e delle infezione da altri patogeni a prevalente localizzazione polmonare (micobatteri non tubercolari, actinomiceti e nocardia).
2015
- INTERSTIZIOPATIA POLMONARE NON CLASSIFICABILE O SECONDARIA A CONNETTIVITE INDIFFERENZIATA. IMPORTANZA E DIFFICOLTÀ DI UNA DIAGNOSI DIFFERENZIALE.
[Abstract in Rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cerri, Stefania; DELLA CASA, Giovanni; Vacchi, Caterina; Giuggioli, Dilia; Colaci, Michele; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Introduzione. Le interstiziopatie polmonari rappresentano un ampio gruppo di malattie che causano fibrosi o infiammazione del parenchima polmonare. Le principali forme sono quelle secondarie ad esposizione ambientale, fibrosi polmonari idiopatiche, polmoniti interstiziali non specifiche (NSIP), forme secondarie a sarcoidosi e quelle secondarie alle connettiviti. Quando per qualche motivo (limiti diagnostici, fattori confondenti, quadri atipici, ecc.) non è possibile classificare un’interstiziopatia nei sottotipi soprariportati, questa viene definita come non classificabile (U-ILD). Le connettiviti indifferenziate (UCTD) sono malattie sistemiche caratterizzate da caratteristiche cliniche e sierologiche tipiche di altre connettiviti definite ma che non ne soddisfano i criteri classificativi esistenti. Il coinvolgimento polmonare è raramente descritto in pazienti affetti da UCTD e non è solitamente considerato a fini diagnostici e classificativi come possibile manifestazione d’esordio. Recentemente alcuni autori hanno suggerito che alcune interstiziopatie non classificabili potrebbero essere meglio inquadrate come secondarie a connettiviti. Nella pratica clinica, soprattutto quando il quadro respiratorio sembra essere il sintomo d’esordio della patologia, la diagnosi differenziale può essere estremamente complessa, eppure di sostanziale importanza alla luce delle implicazioni terapeutiche.
Scopo dello studio. Individuare le caratteristiche cliniche e sierologiche che distinguono le U-ILD dalle interstiziopatie secondarie ad UCTD (UCTD-ILD) per migliorare la diagnosi differenziale e individuare pazienti candidati a terapia immunosoppressiva.
Metodi. Fra settembre 2011 a novembre 2014, 50 pazienti valutati presso il nostro centro venivano classificati come affetti da UCTD o U-ILD, dopo discussione interdisciplinare, secondo i criteri presenti in letteratura. Il quadro radiologico rilevato alla TC ad alta risoluzione veniva classificato come usual interstitial pneumonia (UIP) definito, possibile o non compatibile, secondo i criteri classificativi della fibrosi polmonare idiopatica.
Risultati. Le principali caratteristiche dei pazienti sono riportate nella tabella. Il fenomeno di Raynaud, la xeroftalmia e la positività dell’ANA test risultavano più frequenti nei pazienti con UCTD (rispettivamente p=0.27, p=0-07, p=0.2). Un pattern radiologico non compatibile con UIP veniva rilevato in circa il 70% dei pazienti con UCTD. Un modello predittivo basato su fenomeno di Raynaud, xeroftalmia, positività dell’ANA test mostrava un valore predittivo dell’85,7% (le UCTD venivano classificate nel 90,5% e le U-ILD nel 78,6%).
Conclusioni. Il coinvolgimento polmonare è una possibile manifestazione d’esordio delle UCTD. La diagnosi differenziale con le U-ILD può essere problematica ma è assolutamente necessaria per le conseguenti implicazioni nell’approccio terapeutico. A questo scopo, un’attenta valutazione di alcune caratteristiche cliniche e sierologiche può essere di aiuto. Un lavoro in team multidisciplinare che includa reumatologo, pneumologo, radiologo, anatomo-patologo rappresenta l’approccio migliore al paziente con interstiziopatia polmonare da definire.
2015
- Levels of circulating endothelial cells are low in idiopathic pulmonary fibrosis and are further reduced by anti-fibrotic treatments
[Articolo su rivista]
DE BIASI, Sara; Cerri, Stefania; Bianchini, Elena; Gibellini, Lara; Persiani, Elisa; Montanari, Gloria; Luppi, Fabrizio; Carbonelli, Cristiano Matteo; Zucchi, Luigi; Bocchino, Marialuisa; Zamparelli, Alessandro Sanduzzi; Vancheri, Carlo; Sgalla, Giacomo; Richeldi, Luca; Cossarizza, Andrea
abstract
Background: It has been suggested that circulating fibrocytes and endothelial cells actively participate in the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis (IPF). Indeed, fibrotic areas exist that have fewer blood vessels, whereas adjacent non-fibrotic tissue is highly vascularized. The number of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair. Thus, fibrocytes as well as endothelial cells could potentially be used as biomarkers of disease progression and treatment outcome. Methods: Peripheral blood samples were collected from 67 patients with a multidisciplinary diagnosis of IPF and from 45 age-matched and sex-matched healthy volunteers. Buffy coat was isolated according to standard procedures and at least 20 million cells were stained with different monoclonal antibodies for the detection of CEC, EPC and circulating fibrocytes. For the detection of CEC and EPC, cells were stained with anti-CD45, anti-CD34, anti-CD133, anti-CD14, anti-CD309 and with the viability probe Far-Red LIVE/DEAD. For the detection of circulating fibrocytes, cells were first stained with LIVE/DEAD and the following monoclonal antibodies: anti-CD3, anti-CD19, anti-CD45, anti-CD34 and anti-CD14, then cells were fixed, permeabilized and stained with fluorochrome-conjugated anti-collagen I monoclonal antibodies. Results: Patients with IPF displayed almost undetectable levels of circulating fibrocytes, low levels of CEC, and normal levels of EPC. Patients treated with nintedanib displayed higher levels of CEC, but lower levels of endothelial cells expressing CD309 (the type II receptor for vascular endothelial growth factor). Treatment with both nintedanib and pirfenidone reduced the percentage of CEC and circulating fibrocytes. Conclusions: Levels of CEC were reduced in patients with IPF as compared to healthy individuals. The anti-fibrotic treatments nintedanib and pirfenidone further reduced CEC levels. These findings might help explain the mechanism of action of these drugs and should be explored as predictive biomarkers in IPF.
2015
- Medicina personalizzata e fibrosi polmonare idiopatica
[Articolo su rivista]
Cerri, Stefania; Luppi, Fabrizio
abstract
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP). IPF shows a high variability in the evolution from one patient to another, and between different periods in time in a given individual, showing great clinical heterogeneity. Therefore, predicting the outcome and the response to treatment in IPF is challenging, but potentially very useful, particularly in the single IPF patient. In the last decade, with the common use of proteomic and genomic technologies, our knowledge about the pathogenesis of the disease dramatically improved and it has led to the recognition of various treatment targets and numerous potential biomarkers. Molecular biomarkers are needed in IPF, where they can simplify drug development, facilitate early detection, increase prognostic accuracy and inform treatment recommendations. Although there are not yet validated biomarkers in IPF, some of them are in the proximity to be validated and have demonstrated their potential to improve clinical predictors beyond that of routine clinical practice.
2015
- Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy
[Articolo su rivista]
Sgalla, Giacomo; Cerri, Stefania; Ferrari, Roberto; Ricchieri, Maria Pia; Poletti, Stefano; Ori, Margherita; Garuti, Martina; Montanari, Gloria; Luppi, Fabrizio; Petropulacos, Kyriakoula; Richeldi, Luca
abstract
Background Chronic, progressive respiratory symptoms are associated with great psychological and emotional impact in patients suffering from interstitial lung disease (ILD). This single-centre pilot study evaluated for the first time the safety, feasibility and efficacy of a Mindfulness Based Stress Reduction Program (MBSR) in a group of patients with ILD.
Methods Prospective observational study set in a university hospital ILD outpatient clinic. Nineteen patients with different ILDs were recruited 2 months prior to the start of the 8-week MBSR program and followed up for 12 months. Primary outcomes were program safety and feasibility, while secondary outcomes were changes in moods and stress (assessed by Profile Of Mood State (POMS) and Perceived Stress Scale (PSS) questionnaires), symptoms (Shortness Of Breath (SOB) and Cough And Sputum Assessment (CASA-Q) questionnaires), lung function and exercise tolerance at 12 months.
Results Two patients (10.5%) dropped out in the observational period before the start of the MBSR intervention because of non-respiratory causes. All 17 patients who entered the 8-week MBSR program managed to complete it with an adherence average of eight sessions of nine. No adverse events related to the mindfulness training were reported. Statistically significant improvements in the POMS total score and in several individual items of POMS and PSS were observed throughout the study. However, respiratory questionnaire scores, lung function and exercise tolerance did not show a significant difference over time.
Conclusions An MBSR program appears to be safe and feasible in patients with ILD, and might affect perceived moods and stress producing a positive and lasting improvement in several stress-related negative domains. These findings pave the way to larger (possibly multicentre), randomised, controlled confirmatory trials.
2015
- Morbidity and Mortality in Patients with Idiopathic Pulmonary Fibrosis Undergoing Diagnostic Surgical Lung Biopsy
[Abstract in Atti di Convegno]
Zelent, Gabriele; Cerri, Stefania; Sghedoni, Enrico; Montanari, Gloria; Taddei, Sofia; Aramini, Beatrice; Rossi, Giulio; Stefani, Alessandro; Torricelli, Pietro; Morandi, Uliano; Luppi, Fabrizio
abstract
Morbidity and Mortality In Patients With Idiopathic Pulmonary Fibrosis Undergoing Diagnostic Surgical Lung Biopsy.
2015
- Predictive Value of DLCO Reduction in Scleroderma Patients Without Cardio-Pulmonary Involvement at Baseline
[Abstract in Rivista]
Colaci, Michele; Giuggioli, Dilia; Sebastiani, Marco; Manfredi, Andreina Teresa; Lumetti, Federica; Luppi, Fabrizio; Cerri, Stefania; Ferri, Clodoveo
abstract
Background Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH).
However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications.
Objectives To investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients.
Methods Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre.
Patients with DLCO <55%1 (15 patients; group A) were compared with those with normal DLCO (82 patients; group B), at baseline and at the end of follow-up.
Results At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs. 48/82, 58.5%; p=0.044). More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years), pre-capillary PAH (right heart catheterization) solely developed in some patients of group A (3/15, 20% vs. 0/82; p=0.003).
Conclusions In SSc patients, the presence at baseline of isolated, marked DLCO reduction (<55% of predicted) and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory.
2015
- Predictive value of isolated DLCO reduction in systemic sclerosis patients without cardio-pulmonary involvement at baseline
[Articolo su rivista]
Colaci, Michele; Giuggioli, Dilia; Sebastiani, Marco; Manfredi, Andreina Teresa; Lumetti, Federica; Luppi, Fabrizio; Cerri, Stefania; Ferri, Clodoveo
abstract
Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. The objective was to investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO <55% (15 patients; group A) were compared with those with normal DLCO (82 patients; group B), at baseline and at the end of follow-up. At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs 48/82, 58.5%; p=0.044). More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years), pre-capillary PAH (right heart catheterization) solely developed in some patients of group A (3/15, 20% vs 0/82; p=0.003). In SSc patients, the presence at baseline of isolated, marked DLCO reduction (<55% of predicted) and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory.
2015
- Pulmonary fibrosis and the many faces of UIP
[Capitolo/Saggio]
Cerri, Stefania; Sgalla, Giacomo; Rossi, Giulio; Della Casa, Giovanni; Richeldi, Luca
abstract
Interstitial lung diseases (ILDs) represent a heterogeneous group of clinical entities among which disease of unknown causes may mimic ILDs due to known causes [ 1 ]. Clinical, radiographic and histopathology presentation can largely overlap between different entities and a multidisciplinary approach is proven to be essential in composing the puzzle to reach the most likely clinical diagnosis in each single patients [ 2 ]. The defi nition of specifi c radiographic (on chest high-resolution computed tomography, HRCT) and histopathology
(on lung surgical lung biopsy, SLB) patterns has provided a common terminology in the fi eld of ILDs in the tentative of classifying entities presenting with distinctive features. These patterns have been proposed in the classifi cation of idiopathic interstitial pneumonias (IIPs) [ 3 ], and then have been applied to describe ILDs due to secondary known causes, particularly those related to connective-tissue diseases. Among all these patterns, the usual interstitial pneumonia (UIP) pattern has received more emphasis, in particular since it identifies patients with idiopathic pulmonary fibrosis (IPF), as outlined in the most recent evidence based international guideline [ 4 ]. In this document, specific HRCT and SLB criteria for the defi nition of a defi nite UIP pattern have been proposed and since then they have been widely used as reference standard both in clinical practice and in the defi nition of eligibility criteria for randomized clinical trials. However, while a defi nite UIP pattern can be diagnostic for IPF in the proper clinical context, it is well known that the same pattern can be present in fibrotic lung diseases other than IPF, with important consequences in terms of therapeutic management and prognosis. This chapter will provide an overview on how the UIP pattern is defined, both on radiologist’s view and on pathologist’s view, along with elements that might be helpful in distinguishing an idiopathic UIP pattern from similar appearance in secondary diseases.
2015
- Sindrome di Goodpasture
[Capitolo/Saggio]
Cerri, Stefania
abstract
Il capitolo tratta definizione, epidemiologia, patogenesi, manifestazioni cliniche, diagnosi e terapia della sindrome di Goodpasture.
2015
- UNCLASSIFIABLE INTERSTITIAL LUNG DISEASE OR UNDIFFERENTIATED CONNECTIVE TISSUE DISEASE? A CHALLENGING DIFFERENTIAL DIAGNOSIS
[Abstract in Rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cerri, Stefania; DELLA CASA, Giovanni; Giuggioli, D.; Vacchi, Caterina; Colaci, Michele; Spinella, Amelia; Luppi, Fabrizio; Ferri, Clodoveo
abstract
Background: Interstitial lung disease (ILD) includes a group of disorders of the pulmonary parenchyma including ILD secondary to environmental exposure, to sarcoidosis and connective tissue diseases, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonitis. Unclassifiable-ILD (U-ILD) is defined when ILD cannot be included in one of these subtypes, because of inadequate findings or impossibility to complete diagnostic iter. Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune diseases characterized by clinical and serological features typical of other CTD, but not fulfilling any of the existing classification criteria. It has been recently suggested that UCTD should be responsible for ILD, although the available classification criteria do not consider lung manifestations. Differential diagnosis between U-ILD or ILD secondary to UCTD (UCTD-ILD) can be difficult, but fundamental for therapeutic implications.
Objectives: To evaluate the clinical and serological features of patients with ILD secondary to UCTD compared to unclassifiable ILD, to improve differential diagnosis and identify patients candidate to immuno-suppressive therapy. Secondary outcome was to construct a clinical algorithm, using a priori variables, helpful to predict ILD-UCTD in clinical practice.
Methods: From September 2011 to November 2014, 50 patients referred to our Center were diagnosed for UCTD (26/50) or U-ILD (24/50), after a multidisciplinary discussion according to standard available criteria.
Results: Main features and comparison between UCTD-ILD and U-ILD are reported in the table. An inconsistent with usual interstitial pneumonia (UIP) pattern at high resolution computerized tomography (HRCT) was more frequently detected in UCTD-ILD compared to U-ILD. A predictive model based on Raynaud's phenomenon, ocular dryness, and antinuclear antibodies showed a predictive value of 85.7% (UCTD-ILD were correctly classified in 90.5% and U-ILD in 78.6%).
Clinical and demographic features of patients with interstitial lung disease
UCTD U-ILD p
Number of patients 26 24
Sex 19F/7M 14F/10M ns
Age at diagnosis 61.7±12.7 67.1±9.1 ns
Raynaud's phenomenon 68.0% 29.4% 0.027
Oral dryness 60.0% 35.3% ns
Ocular dryness 60.0% 13.3% 0.007
Schirmer test 41.6% 4.2% 0.006
Arthritis 19.2% 0 0.05
Skin manifestations 30.4% 0 0.029
Thrombocytopenia 16.7% 18.2% ns
Anemia 33.3% 18.2% ns
Antinuclear antibodies 87% 52.4% 0.02
ENA 38.1% 10% ns
Rheumatoid factor 13.6% 9.1% ns
UIP pattern to HRCT 41.2% 58.8% ns
Inconsitent with UIP pattern to HRCT 66.7% 33.3% ns
Conclusions: Lung involvement is a possible presenting symptom of UCTD; therefore, differential diagnosis with U-ILD is crucial due to the relevant therapeutic implications; a multidisciplinary approach, including rheumatologist, pulmonologist, radiologist, and pathologist, is mandatory. Some clinical-serological features potentially helpful in differential diagnosis should be carefully evaluated
2014
- A quantitative proteomic approach to identify significantly altered protein networks in the serum of patients with lymphangioleiomyomatosis (LAM)
[Articolo su rivista]
Banville, Nessa; Burgess, JANETTE KAY; Jaffar, Jade; Tjin, Gavin; Richeldi, Luca; Cerri, Stefania; Persiani, Elisa; Black, Judith L.; Oliver, Brian G.
abstract
Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition affecting approximately 3.4-7.5/million women, with an average lag time between symptom onset and diagnosis of upwards of 4 years. The aim of this work was to identify altered proteins in LAM serum which may be potential biomarkers of disease. Serum from LAM patient volunteers and healthy control volunteers were pooled and analysis carried out using quantitative 4-plex iTRAQ technology. Differentially expressed proteins were validated using ELISAs and pathway analysis was carried out using Ingenuity Pathway Analysis. Fourteen proteins were differentially expressed in LAM serum compared to control serum (p<0.05). Further screening validated the observed differences in extracellular matrix remodelling proteins including fibronectin (30% decrease in LAM, p = 0.03), von Willebrand Factor (40% reduction in LAM, p = 0.03) and Kallikrein III (25% increase in LAM, p = 0.03). Pathway networks elucidated the relationships between the ECM and cell trafficking in LAM. This study was the first to highlight an imbalance in networks important for remodelling in LAM, providing a set of novel potential biomarkers. These understandings may lead to a new effective treatment for LAM in the future. © 2014 Banville et al.
2014
- Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis
[Articolo su rivista]
Jaffar, Jade; Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, JANETTE KAY
abstract
BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry.RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease ( P 5 .006). Furthermore, tissue fi bulin-1 levels were increased in patients with IPF ( P 5 .02) and correlated negatively with lung function ( r 5 2 0.9, P , .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF ( P , .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P 5 .012).CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.
2014
- HRCT Patterns Of Usual Interstitial Pneumonia In Rheumatoid Lung
[Abstract in Rivista]
Tonelli, Roberto; Sverzellati, Nicola; DELLA CASA, Giovanni; Spagnolo, Paolo; Cerri, Stefania; Manfredi, Andreina Teresa; Sebastiani, Marco; Cocconcelli, Elisabetta; DEL GIOVANE, Cinzia; Balduzzi, Sara; Richeldi, Luca; Torricelli, Pietro; Ferri, Clodoveo; Luppi, Fabrizio
abstract
RATIONALE. Interstitial lung disease (ILD) is a well-recognized complication of rheumatoid arthritis (RA) and can present with different patterns on high-resolution computed tomography (HRCT) of the chest. It has been recently shown that a definite HRCT usual interstitial pneumonia (UIP) pattern is highly specific and moderately sensitive for a histopathologic UIP pattern. The aims of the present study were: i) to evaluate the prevalence of the UIP pattern on HRCT in patients with RA-ILD, as compared with patients with idiopathic pulmonary fibrosis (IPF) and ii) to assess the level of agreement between two experienced chest radiologists in detecting the UIP pattern in the two groups of patients.
METHODS. 30 patients with RA and at least one chest HRCT showing interstitial changes were retrospectively identified from a single-center cohort of RA patients. Fifty-two patients with IPF based on current diagnostic criteria served as diseased controls. For patients who had more than one HRCT the more recent HRCT was selected. Two experienced thoracic radiologists (radiologist A and B) blinded to patient diagnosis scored all HRCT images independently. Radiologic patterns were categorized as definite UIP, possible UIP or inconsistent with UIP according to the most current international guidelines. The prevalence of the different patterns was assessed for both groups and compared by using the chi square test. The concordance between radiologists was determined using the Cohen kappa score.
RESULTS. Radiologist A detected 4 definite UIP (13%), 10 possible UIP (33%) and 16 inconsistent with UIP patterns (53%) among patients with RA-ILD and 16 definite UIP (30%), 24 possible UIP (46%) and 12 inconsistent with UIP patterns (23%) among patients with IPF (chi square 0.016). Radiologist B identified 6 definite UIP (20%), 9 possible UIP (30%) and 15 inconsistent with UIP patterns (50%) in the RA-ILD group and 23 definite UIP (44%), 16 possible UIP (30%) and 13 inconsistent with UIP patterns (25%) in the IPF group (chi square 0.036).
Diagnostic agreement in UIP pattern detection was 71.2% (κ= 0.57) for the IPF group and 76.7% (κ =0.62) for the RA-ILD group.
CONCLUSIONS. A definite UIP pattern can be identified in chest HRCT of a sizeable fraction of patients with RA-ILD. Moreover, the possible UIP pattern appears to be almost equally distributed in patients with RA-ILD and IPF. Of note, the level of agreement between two experienced chest radiologists in detecting the UIP pattern is higher in patients with RA-ILD than in IPF.
2014
- Identification Of Potential Candidate Biomarkers In Lymphangioleiomyomatosis Using ITRAQ Proteomic Technology
[Abstract in Rivista]
Banville, Nessa J; Burgess, JANETTE KAY; Jaffar, Jade; Richeldi, Luca; Cerri, Stefania; Black, Judith L; Oliver, Brian G.
abstract
Study Rational: Lympangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition that affects between 3-7/million women. It manifests primarily in women of child-bearing age, with an average lag time between symptom onset and definitive diagnosis of upwards of 4 years.
Currently no reliable biomarker exists for patients with LAM, therefore, identifying a predictive or prognostic disease biomarker could reduce diagnosis lag time, as well as increase our knowledge of the underlying disease mechanisms in this multifactorial condition.
This study hypothesized that there were significant alterations in the protein content in serum between LAM patients and healthy aged-matched controls.
Study Aim: Identification of potential candidate biomarkers in LAM patient serum.
Methods: Serum from LAM patient volunteers (n= 3, n= 5) and healthy aged matched control volunteers (n= 4, n= 5) were pooled and two runs of high-throughput protein analysis were carried out using 4-plex iTRAQ technology on a Triple TOF 5600 (AB Sciex). After network pathway analysis, using Ingenuity Pathway Analysis software™, a number of the differentially expressed proteins (Fibronectin, von Willebrand Factor and Kallikrein III) were validated using ELISA in a wider individual patient cohort (n= 18) and an age matched healthy
control group (n= 12).
Results: A total of 14 proteins were differentially expressed in LAM serum compared to healthy age-matched control serum (p<0.05). It was found that an intricate network of cell trafficking proteins was altered. Differential expression of the remodelling proteins fibronectin (decreased expression of 30% in LAM sera, p = 0.03), von Willebrand Factor (vWF, 40% reduction in LAM, p = 0.03) and the serum protease Kallikrein III (KLK3, 25% increase in LAM, p = 0.027) were identified in pooled circulating LAM sera and subsequently validated in individual samples.
Conclusion: This study demonstrates, for the first time, that in LAM a substantial imbalance exists in protein networks important for remodelling, particularly in the circulating levels of the structural proteins; fibronectin, vWF and KLK3. We have also revealed an intricate network of significantly altered proteins involved in cell trafficking, an integral component of LAM disease progression. These results provide a set of novel candidate biomarkers which may be useful for the development of a feasible approach to diagnosis, and potentially lead to a new effective targeted treatment for LAM.
2014
- Inappropriatezza prescrittiva dell'ossigenoterapia domiciliare a lungo termine
[Articolo su rivista]
Sdanganelli, Antonia; Lusuardi, Mirco; Soncini, Francesco; Maini, Maurizio; Bottrighi, Pietro; Dallari, Rossano; Giovannini, Michele; Casolari, Loretta; Campagna, Anselmo; Richeldi, Luca; Cerri, Stefania
abstract
Long-term oxygen therapy (LTOT) at home is an established treatment, which is potentially subjected to inappropriate prescription. This retrospective study aims to identify the determinants of inappropriate prescription through the analysis of existing prescribing information for LTOT and routes of supply within the Northern area of the Emilia-Romagna Region. We selected all first time prescriptions for LTOT released in 2009 in the provinces of Modena, Parma, Piacenza and Reggio Emilia. A specific questionnaire with data collection through an electronic database allowed to analyze both organizational / administrative and clinical variables related to LTOT prescription. We analyzed a total of 364 prescriptions: 62 from Modena, 96 from Parma, 73 from Reggio Emilia, and 133 from Piacenza. The data collected highlighted several differences in the prescribing process between the four provinces. Among the most frequently omitted information in the prescription we identified: a) values of PaO2 and PaCO2 (absent in more than 90% of prescriptions dispensed at the AUSL Modena, while present in about 70% of prescriptions in Parma and in almost all of those of Piacenza and Reggio Emilia); b) differential information on oxygen flow at night or during exercise (absent in the prescriptions from Parma, Modena and Piacenza and present in more than 60% of prescriptions from Reggio Emilia); c) indications concerning the follow-up (not covered in the prescriptions from Modena and Parma). Finally, definition of the diagnosis that justifies the need for prescription of LTOT is often missing or incomplete. Therefore the results of the study have allowed the identification of some factors of inappropriateness both on the clinical side and on the management side. This analysis indicates the need for interventions aimed at improving and standardizing the process of LTOT prescription.
2014
- Lung fibrosis, bone marrow fibrosis and liver cirrhosis: A Short Telomere Syndrome or a casual association?
[Articolo su rivista]
Carulli, Lucia; Anzivino, Claudia; Bertolotti, Marco; Loria, Paola; Richeldi, Luca; Cerri, Stefania
abstract
Background: Telomere-mediated disease has diverse presentations that span the age spectrum. Their type, age of onset,
and severity depend on the extent of the telomere length defect. During adult life, telomerase mutations may represent risk
factors rather than genetic determinants and need other factors to contribute to disease development. This is case of
diseases such as aplastic anemia, pulmonary fibrosis and liver cirrhosis which may occur as single disease or together in a
syndromic clustering. Here we report a case of a man most likely affected by a short telomere syndrome.
Case report: A 58 years old man, presented for evaluation of pulmonary fibrosis diagnosed few years earlier in a different
medical center. He also presented a mild bone marrow fibrosis and a liver cirrhosis, both diagnosed one year prior
evaluation with a bone marrow analysis and liver biopsy. The patient was an active smoker, obese, with digital clubbing
and inspiratory Velcro crackles at the right lower lobe. Laboratory tests showed thrombocytopenia and liver enzymes
alteration. He rapidly developed ascites and progression of the pulmonary fibrosis, the patient became oxygen-dependent
in few months.
Methods: Sequencing and mutation analysis of hTERT and hTERC genes, Leukocyte Telomere length (LTL) and
Telomerase activity (TA) were evaluated.
Results: In our patient LTL was shorter and TA reduced compared to the controls. Genes sequencing did not show any
hTERT and hTERC mutations.
Conclusions: This is a report on a short telomere syndrome involving lung, liver and bone marrow, associated to very
short telomere and absent telomerase activity not in the setting of dyskeratosis congenita.
The fact that short telomeres mediate inflammation and fibrosis provides a rationale for pursuing translational strategies
aimed at preventing telomere shortening or its cellular consequences as a therapeutic approach
2014
- Lung involvement in systemic sclerosis: role of high resolution computed tomography and its relationship with other pulmonary and clinico-serological features.
[Articolo su rivista]
Colaci, Michele; Sebastiani, Marco; Manfredi, Andreina Teresa; Giuggioli, D; Cassone, Giulia; Manzini, Cu; Ghizzoni, C; Cerri, Stefania; Ferri, Clodoveo
abstract
The study investigated the characteristic of interstitial lung disease in a large series of systemic sclerosis (SSc) patients by means of HRCT and the correlations between functional lung parameters, serological features and the extent of lung involvement evaluated by high-resolution computed tomography (HRCT). One hundred and seven SSc patients, consecutively investigated by means of HRCT, standard chest X-ray, and pulmonary function tests, were retrospectively evaluated. Chest radiogram and HRCT scores were strongly associated (Pearson 's r=0.82, p < .0001); moreover, the first significantly correlated with spirometric parameters, even if weakly. Anti-Scl70 and anti-centromere antibodies were associated with higher (p=0.01) and lower HRCT score (p=0.0002), respectively. The extension of interstitial lung involvement in SSc evaluated with HRCT is directly proportional to functional lung parameters. HRCT, spirometry and DLco should be considered essential in the core-set of non-invasive diagnostic tools for the first-line assessment of scleroderma lung involvement.
2014
- Prevalence Of Subclinical Liver Fibrosis Among Patients With Idiopathic Pulmonary Fibrosis
[Abstract in Rivista]
Cocconcelli, Elisabetta; Cerri, Stefania; Spagnolo, Paolo; Tonelli, Roberto; Ventura, Paolo; Abbati, Gianluca; Vegetti, Alberto; Pileri, Francesca; DEL GIOVANE, Cinzia; Balduzzi, Sara; Pietrangelo, Antonello; Richeldi, Luca; Luppi, Fabrizio
abstract
Rationale
Idiopathic pulmonary fibrosis (IPF) is a specific form of progressive fibrosing interstitial pneumonia of unknown cause. Common pathogenic mechanisms with chronic fibrotic disorders involving other organs are likely. Yet, data on the co-existence of subclinical fibrotic disease across multiple organs in patients with IPF are lacking. The present study aimed to investigate the prevalence of subclinical liver fibrosis among patients with IPF.
Methods
Patients referred to the Center for Rare Lung Disease of the University Hospital of Modena, with a diagnosis of IPF according to recent guidelines and without previous history of liver diseases underwent hepatic transient elastography (FibroScan®), a non-invasive technique measuring liver stiffness, which routinely used for the assessment of hepatic fibrosis in patients with chronic liver diseases. Hepatic fibrotic status is expressed in a scale from 0 (absence of hepatic fibrosis) to 4 (severe liver fibrosis / cirrhosis). Patients with body mass index (BMI) ≥29 (confidence limit of the instrument) were excluded. Patients, in which any degree of hepatic fibrosis was detected, underwent screening for possible secondary causes of liver fibrosis.
Results
Among 48 IPF patients (34 males, mean age 69 years), 11 (23%) were excluded because of high BMI. In 8 out 37 patients (22%) it was not possible to obtain successful measurements due to the excess of subcutaneous adipose tissue in the chest wall, or narrow intercostal spaces. Thirteen of 37 patients (35%) had abnormal hepatic transient elastography results: 4 patients fell within the range F1-F2 (6.1-7.6 kPa), 6 in F2 (7.4-8.4 kPa), one in F2-F3 (9.5 kPa), 1 in F4 (14.3 kPa) and 1 was identified as probable fibrosis not otherwise classifiable. In all cases, secondary causes of hepatic fibrosis were excluded. Minor impairment of markers of liver injury was found in a minority of patients with liver fibrosis, with AST and ALT values exceeding the threshold value respectively in 2 and 3 patients with liver fibrosis, detected on elastography.
Conclusions
Over one third of patients in this IPF cohort had a concomitant fibrosing subclinical process in the liver. These preliminary data prompt the need for a large prospective study aimed at clarifying the correlation between the fibrosing processes in the lung and in the liver and the possibility of shared pathogenic mechanisms.
2014
- RHEUMATOID ARTHRITIS RELATED INTERSTITIAL LUNG DISEASE. RADIOLOGICAL PATTERNS AND CORRELATIONS WITH CLINICAL, SEROLOGICAL AND DEMOGRAPHIC FEATURES OF DISEASE
[Abstract in Rivista]
Sebastiani, Marco; Manfredi, Andreina Teresa; Tonelli, Roberto; Spagnolo, Paolo; Campomori, Federica; Vacchi, Caterina; Cocconcelli, Elisabetta; Cerri, Stefania; Colaci, Michele; Luppi, Fabrizio; DELLA CASA, Giovanni; Sverzellati, N; Torricelli, Pietro; Richeldi, Luca; Ferri, Clodoveo
abstract
RHEUMATOID ARTHRITIS RELATED INTERSTITIAL LUNG DISEASE. RADIOLOGICAL PATTERNS AND CORRELATIONS WITH CLINICAL, SEROLOGICAL AND DEMOGRAPHIC FEATURES OF DISEASE
2013
- Levels Of Fibulin-1 In The Lung And Serum Are Increased In Fibrotic Interstitial Lung Disease
[Abstract in Rivista]
Jaffar, Jade; Unger, Sofia; Corte, Tamera; Wolters, Paul J; Richeldi, Luca; Cerri, Stefania; Argraves, W. S; Oliver, Brian G; Black, Judy L; Burgess, JANETTE KAY
abstract
RATIONALE: Excessive pulmonary extracellular matrix (ECM) deposition leads to a progressive, permanent change in lung architecture that, in extreme cases, results in respiratory failure. Fibulin-1 (FBLN1), fibronectin (FN) periostin (PO) and tenascin-C (TNC) are ECM associated proteins that are increased in several diseases. The aim of this study was to measure levels of these proteins in the airway, parenchyma and serum of patients with a range of fibrotic lung diseases and determine the relationship between these levels and the degree of fibrosis. METHODS: Immunohistochemistry (IHC) was performed on paraffin-embedded formalin fixed tissue sections from patients with no lung disease and Idiopathic pulmonary fibrosis (IPF) (n=5-8 each) from 3 cohorts (Sydney, Perth, and Modena). Staining intensity was analysed by ImageJ to assess FBLN1 protein levels in tissue. Serum and pulmonary function tests from patients with interstitial lung disease (ILD) were collected from 3 cohorts (Sydney, Modena and San Francisco). Serum levels of FBLN1, PO, TNC and FN were analysed by western blot and sandwich ELISA. RESULTS: The level of FBLN1 immunostaining in the airways and parenchyma of patients with IPF was significantly increased compared to that of non-diseased individuals (n=4-5; p=0.02, n=5-8; p=0.001 respectively). The level of immunostaining for PO in the parenchyma of patients with IPF was significantly increased compared to those of non-diseased individuals (n=4-9; p=0.01). Serum levels of FBLN1 and PO but not TNC or FN were significantly increased in patients with IPF (n=44) from all three cohorts compared to non-diseased controls (n=17) (p<0.001) (Figure 1). Serum levels of FBLN1, in patients with ILDs were associated with fibrotic disease severity (Figure 2), as represented by composite physiologic index (R=0.404; p<0.001), DLco% predicted (R=-0.358; p=0.003), and FVC% predicted (R=-0.326; p=0.005).CONCLUSIONS: FBLN1 deposition is increased in both the airway and parenchyma of patients with IPF. Serum FBLN1 levels are elevated in patients with fibrotic ILD and are associated with the degree of fibrosis. Although serum PO levels and serum FBLN1 levels were associated with DLco and composite physiologic index, only FBLN1 was associated with FVC. Findings from this study indicate that FBLN1 is a novel IPF biomarker and raise the possibility that it can be used as a target for the development of new treatments for these diseases for which there are few treatment options.
2013
- Long-term management of IPF with pirfenidone - A clinical case study with 5 years follow-up
[Articolo su rivista]
Richeldi, Luca; Sgalla, Giacomo; Cerri, Stefania
abstract
Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-5 years from initial diagnosis.To date, the search for an effective treatment has involved numerous clinical trials of investigational agents but without significant success. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has therefore shifted in accordance with this paradigm change. Emerging clinical data from recently published and ongoing trials investigating new potential pharmacological agents should be considered in the routine clinical management of these patients. Based upon encouraging results from randomised-controlled trials showing a positive effect in slowing decline in pulmonary function and reducing disease progression, pirfenidone was approved in 2011 as the first treatment in patients with IPF. This case study describes the clinical course of a patient enrolled into the Phase III and open-label extension studies of pirfenidone.
2013
- Lung cancer in scleroderma: results from an Italian rheumatologic center and review of the literature.
[Articolo su rivista]
Colaci, Michele; Giuggioli, D; Sebastiani, Marco; Manfredi, Andreina Teresa; Vacchi, Caterina; Spagnolo, Paolo; Cerri, Stefania; Luppi, Fabrizio; Richeldi, Luca; Ferri, Clodoveo
abstract
The association between systemic sclerosis (SSc) and cancer was widely described, particularly with breast and lung carcinoma; while, data regarding possible associations between cancer and SSc features are still scarce. We retrospectively evaluated the prevalence of lung cancer in our SSc patient cohort (318 SSc patients, 31 M and 287 F, age 51.5±14.5SD years, disease duration 10.3±6.5SD years) and clinico-serological factors potentially associated to the development of this malignancy. A review of the world literature about this topic was also done. We found that lung cancer complicated 16/318 (5%) SSc patients; namely 11/287 females (4%) and 5/31 males (16.1%). Median age of SSc patients with lung cancer was 54 (range 38-72) years for female patients, and 63 (range 40-73) for males; 13/16 patients died because of the neoplasia. Considering the incidence of lung carcinoma in sex/age-matched general population of the same geographical area, the percentages of lung cancer in our SSc series are about 2.5 and >5 times higher for male and female patients, respectively. The presence of lung cancer significantly correlated with male sex (p=0.011), presence of anti-Scl70 antibodies (p=0.0007), cyclophosphamide therapy (p=0.0001), forced vital capacity (FVC) <75% (p=0.0001), and lung fibrosis (p=0.0127); moreover patients with cancer have a significantly lower age at the diagnosis of SSc (p=0.009) and longer disease duration (p=0.0175). The logistic regression analysis confirmed a significant association with the anti-Scl70 antibodies (OR 6.4, 95%IC 1.7-24.1; p=0.006) and the reduction of FVC (OR 6.7, 95%IC 2.2-20.7; p=0.001) only. Overall, the prevalence of lung cancer in the subset of SSc patients with anti-Scl70 antibodies was 12/105 (11.4%), 9/40 (22.5%) in patients with FVC% reduction, and 7/22 (31.8%) in patients with both. In literature, the median prevalence of lung cancer in SSc series was 2.4% (range 0-4.2%); even if sporadic, associations with lung involvement or antiScl70 autoantibodies were raised, according to our findings. Our study confirmed the higher frequency of lung cancer among SSc patients compared to general population, particularly within patients' subset with serum anti-Scl70 antibodies and lung involvement.
2013
- Malattie infiltrative diffuse del polmone
[Capitolo/Saggio]
Cerri, Stefania; Richeldi, Luca; Spagnolo, Paolo
abstract
Le pneumopatie infiltrative diffuse (PID), comunemente ed erroneamente note come “polmoniti interstiziali” o “fibrosi polmonari”, sono tradizionalmente fonte di confusione, sia perché il termine “interstiziale” è fuorviante (infatti, queste patologie spesso non sono limitate allo spazio alveolo-capillare), sia perché non tutte le PID esitano in fibrosi. Ad oggi
sono state descritte oltre duecento entità nosologiche distinte, alcune ad esclusivo interessamento polmonare, altre in cui il polmone è solo uno degli organi colpiti. Singoli stimoli possono causare l’insorgenza di episodi acuti, ma è in seguito a un’esposizione ripetuta e protratta a uno o più di questi stimoli che la malattia assume un carattere cronico e persistente evolvendo in fibrosi nei casi più severi. Con riferimento all’eziopatogenesi, le PID possono essere classificate in quattro gruppi: da agenti irritanti, da cause immunologiche, idiopatiche e mimi di PID. Tra le PID sono incluse frequentemente, ma erroneamente, anche le polmoniti eosinofile e le vasculiti a prevalente interessamento
polmonare.
2013
- New approaches to the design of clinical trials in idiopathic pulmonary fibrosis
[Articolo su rivista]
Cerri, Stefania; DEL GIOVANE, Cinzia; Balduzzi, Sara; Soncini, Francesco; Sdanganelli, Antonia; Richeldi, Luca
abstract
Idiopathic pulmonary fibrosis (IPF) is one of the major challenges for respiratory medicine since prognosis is particularly poor and few therapeutic options are available - in fact, at present to the only approved drug is pirfenidone. Winning this challenge will be based on successful design and completion of randomized clinical trials. The last decade witnessed an unprecedented increase in quality and quantity of trials in IPF: nonetheless, most have been negative and potential obstacles did emerge. In particular, the choice of the best endpoint, i.e. clinically meaningful and feasible at the same time, and the management of missing data still represent issues not fully resolved. The increasingly competitive environment and the heterogeneity in approach by different regulatory agencies also need to be considered. In the next few years more and more trials will be designed and completed, in the hope of taking quicker and safer treatments to IPF patients.
2013
- Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis
[Articolo su rivista]
Lee, JOYCE SUJIN; Kim, Eunice J.; Lynch, Kara L.; Elicker, Brett; Ryerson, CHRISTOPHER J; Katsumoto, Tamiko R.; Shum, Anthony K.; Wolters, Paul J.; Cerri, Stefania; Richeldi, Luca; Jones, Kirk D.; Talmadge E., King J. r.; Collard, Harold R.
abstract
Background: The clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis is unclear. The objective of this study was to determine the frequency and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. Methods: We measured an extensive panel of autoantibodies (including rheumatoid factor, anti-cyclic citrullinated peptide, and anti-nuclear antibodies by immunofluorescence) associated with connective tissue disease or vasculitis in a cohort of well-characterized patients with idiopathic pulmonary fibrosis (n = 67). The prevalence of circulating autoantibodies was compared between idiopathic pulmonary fibrosis patients and healthy controls (n = 52). We compared the clinical characteristics of patients with and without circulating autoantibodies, and analyzed the relationship between autoantibody positivity and transplant-free survival time. Results: Positive autoantibodies were found in 22% of patients with IPF and 21% of healthy controls. There were no differences in the types of autoantibodies found between patients with idiopathic pulmonary fibrosis and healthy controls. Among patients with idiopathic pulmonary fibrosis, there were no significant differences in clinical characteristics between those with and without circulating autoantibodies. The presence of circulating autoantibodies was associated with longer transplant-free survival time on adjusted analysis, however the significance varied depending on which statistical model was used (HR 0.22-0.47, p value 0.02-0.17). Conclusions: The frequency of circulating autoantibodies in patients with idiopathic pulmonary fibrosis is no different compared to healthy controls, but may be associated with longer survival.© 2012 Elsevier Ltd. All rights reserved.
2013
- Tubercolosi
[Capitolo/Saggio]
Cerri, Stefania; Roversi, Pietro; Richeldi, Luca
abstract
L’infezione da micobatteri tubercolari ha accompagnato la storia dell’uomo sin dall’antichità. Nei secoli la malattia tubercolare ha rappresentato una piaga sociale, principale responsabile di morbidità e mortalità nella popolazione giovane adulta, e ancora oggi costituisce la prima causa di morte per singola malattia infettiva nel mondo, con circa 1,7 milioni di decessi all’anno (WHO, 2011). I progressi nello sviluppo di test diagnostici, nell’utilizzo di regimi terapeutici standardizzati efficaci e nell’adozione di programmi di controllo dell’infezione, hanno prodotto negli ultimi decenni un’inversione di tendenza degli indici di incidenza e prevalenza della malattia (WHO, 2011). Tuttavia, alcuni fattori, tra i quali la co-infezione da virus dell’HIV, il crescente problema dell’emergere di ceppi farmaco-resistenti, i flussi migratori da Paesi ad alta endemia e le condizioni di
immunodepressione (incluse quelle di natura iatrogena, in una popolazione generale che diventa sempre più anziana), rendono ragione della persistenza dell’infezione a livello globale (Dye et al., 2010).
2012
- Genetic testing in diffuse parenchymal lung disease
[Articolo su rivista]
Spagnolo, Paolo; F., Luppi; Cerri, Stefania; Richeldi, Luca
abstract
Diffuse parenchymal lung diseases (DPLD) represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases), the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood.Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice.This review focuses on idiopathic pulmonary fibrosis (IPF) and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF.
2012
- Home Oxygen Saturation Monitoring And Quality Of Life Evaluation In Patients With Idiopathic Pulmonary Fibrosis: Preliminary Results From A Prospective Multicenter Trial
[Abstract in Rivista]
Cerri, Stefania; Soncini, Francesco; Sdanganelli, Antonia; Aiello, Marina; Chetta, Alfredo Antonio; Lusuardi, Mirco; Dallari, Rossano; Balduzzi, Sara; Campagna, Anselmo; Casolari, Loretta; Fabbri, Leonardo; Richeldi, Luca
abstract
Introduction. Long-term follow-up of patients with idiopathic pulmonary fibrosis (IPF) is an important component of their clinical management. While oxygen saturation (SpO2) measurement is widely used in both routine practice and clinical trials, feasibility and clinical relevance of long-term SpO2 monitoring has not been studied yet.
Methods. We designed a 1-year multicenter prospective study aimed at evaluating the long-term feasibility of home daily SpO2 monitoring and its clinical relevance by assessment of correlation with a symptoms and quality of life (QoL) questionnaire. Enrolled patients received a multi-parameter digital recorder (Sally® Personal Assistant, Medigas, Italy), allowing acquisition, transmission and online web-based storage of SpO2 measurements, together with the data of a short questionnaire on symptoms and QoL. SpO2 data were acquired three times a day, for at least one minute, in resting conditions, while answers to the questionnaire were provided once a day. All data were transmitted daily to a dedicated server through the telephone landline. Spearman’s rank correlation coefficient () was used to calculate the correlation between SpO2 values and the QoL scores.
Results. Six months interim analysis was based on 21 IPF patients (15 males, mean age 75 years; 9 receiving long-term oxygen therapy): 17 of them (81%) provided valid data for a mean time (± SD) of 175 (±78) days). The majority (66%) of patients provided sufficient data for calculating the correlation coefficient. In most patients (86%) SpO2 values decreased while QoL score increased (i.e. QoL deteriorated): in 5 the correlation was statistically significant. Patients monitored for longer time were more likely to show a statistically significant correlation between these two parameters. Home SpO2 monitoring was accepted positively by all patients; the majority of them (63%) was able to self-perform all required tasks. Missing data accounted for 41% of all expected data and were mostly due to technical issues during the first weeks of study.
Conclusions. Non-invasive home daily monitoring of oxygen saturation is feasible and well accepted in IPF patients. SpO2 seems to correlate with changes in symptoms and QoL scores, thus confirming the clinical relevance of this parameter.
2012
- Management of idiopathic pulmonary fibrosis.
[Articolo su rivista]
Cerri, Stefania; Spagnolo, Paolo; F., Luppi; Richeldi, Luca
abstract
Idiopathic pulmonary fibrosis (IPF) is a deadly progressive lung disease without an effective standard treatment approach. Because of the complexity and uncertainties of IPF treatment, therapeutic decisions need to be tailored to the individual patient, after discussing the potential benefits and pitfalls. Pirfenidone has been approved for the treatment of IPF in many countries, but is not recommended as a first-choice therapy by current guidelines because of the lack of a definite efficacy. Randomized controlled trials represent a valid choice for patients with IPF, and their completion is important in improving both survival and quality of life.
2012
- Quantiferon-TB Gold In-Tube Tests In Hospital Health Care Workers: A Five Years Experience
[Abstract in Rivista]
Cerri, Stefania; Meccugni, Barbara; Meacci, Marisa; Pietrosemoli, Paola; Balduzzi, Sara; Rumpianesi, Fabio; Marchegiano, Patrizia; Corona, Gianluca; Fabbri, Leonardo; Richeldi, Luca
abstract
Introduction. Interferon Gamma Release Assays (IGRAs) are being largely used worldwide for the screening of tuberculosis infection among subjects likely to undergo multiple testing, such as health care workers (HCW). In theory, IGRAs should overcome the risk of false positive results due to the boosting effect, at difference with the in vivo tuberculin skin test. Evaluation of IGRA results in HCW in a non-experimental setting over several years may provide information on the real-life performance of these tests in daily practice. We reviewed the results of
QuantiFERON-TB In-Tube (QTF-IT) tests performed on HCW over nearly five years, with particular focus on repeated tests.
Methods: We extracted the anonymised electronic records of all consecutive QFT-IT performed on HCW between May 2006 and December 2010. All tests were done at the Laboratory of Microbiology and Virology of University Hospital of Modena (Italy).
Results: A total of 1,531 tests were performed in 1,189 individuals (mean age ± SD: 37±10 years; 29% male). In 226 subjects (37±9 years; 31% male) QFT-IT was repeated at least once. Among subjects who underwent single testing (n=963, 81%), 85% were negative and 14% positive, as compared to the results at first test among subjects with repeated tests (69% negative, 27% positive; p<0.0001). In the majority of cases (84%) a second QFT-IT provided a concordant valid result. Reversion (from positive to negative) occurred more frequently than conversion (from negative to positive) (respectively, 10% vs. 4% of repeated tests). Rate of indeterminate results was extremely low, 0.4% in subjects with single testing and 1.8% at first test in subjects with multiple tests. At second testing, indeterminate QFT-IT results at first testing became negative in all but one case, which remained indeterminate.
Conclusions: In this non-experimental routine setting of tuberculosis infection screening in HCW, subjects who underwent repeated tests were more likely to have a positive QFT-IT at first testing, as compared to subjects with single testing. However, a repeated QFT-IT confirmed previous results in almost all cases. Reversions occurred more often than conversions. Rate of indeterminate QFT-IT results was extremely low, thus indicating a very good technical performance of this test in HCW in a low TB prevalence area.
2012
- Repeated Quantiferon-TB Gold In-Tube Tests In Routine Clinical Practice: A Five Years Experience
[Abstract in Rivista]
Cerri, Stefania; Meacci, Marisa; Meccugni, Barbara; Pietrosemoli, Paola; Balduzzi, Sara; Rumpianesi, Fabio; Fabbri, Leonardo; Richeldi, Luca
abstract
Introduction. Interferon Gamma Release Assays (IGRAs) are increasingly being used as diagnostic aids for Mycobacterium tuberculosis infection. Although evidence on IGRA performance in different populations is quickly accumulating, data on their use in non-experimental settings may provide information on their performance in routine clinical practice. We reviewed the results of QuantiFERON-TB In-Tube (QTF-IT) tests at our hospital since its introduction in diagnostic routine, with particular focus on repeated tests.
Methods: We extracted the anonymised electronic records of all consecutive QFT-IT performed at the Laboratory of Microbiology and Virology of University Hospital of Modena (Italy) between May 2006 and December 2010. All tests performed in both inpatients and outpatients were included in the analysis.
Results: A total of 10,812 tests were performed in 8,623 individuals (mean age ± SD: 46±23 years; 52.8% male). Among subjects who underwent single testing (n=7,039, 81.6%), 69.7% were negative, 22.5% positive, 7.4% indeterminate and 0.1% not interpretable due to high background in the negative control (0.3% of all tests were not performed due to missing or inadequate samples). In 1,584 (18.4%) subjects (mean age ± SD: 41±23 years; 56.1% male) QFT-IT was repeated at least once: in this group, there was a significantly higher proportion of indeterminate QFT-IT results (11.6%) at first testing, as compared to subjects with single tests (p<0.0001). In most cases (72.5%) the second QFT-IT provided valid concordant results (53.5% concordant negative; 19.0% concordant positive); conversions (from negative to positive) and reversions (from positive to negative) occurred in 3.7% and 7.3% of patients, respectively. Indeterminate results were more likely to become negative instead of positive (7.1% vs. 0.8%; p<0.0001); 3.8% of negative results became indeterminate at second testing.
Conclusions: In this non-experimental routine setting, repeated QFT-IT confirmed previous results in most cases, providing little additional clinical information. Indeterminate QFT-IT results were more frequently negative than positive at repeated testing, thus suggesting that most indeterminate tests do not mask a positive result.
2012
- Sarcoidosis: challenging diagnostic aspects of an old disease.
[Articolo su rivista]
Spagnolo, Paolo; F., Luppi; P., Roversi; Cerri, Stefania; Fabbri, Leonardo; Richeldi, Luca
abstract
Over the past few years, there have been substantial advances in our understanding of sarcoidosis immunopathogenesis. Conversely, the etiology of the disease remains obscure for a number of reasons, including heterogeneity of clinical manifestations, often overlapping with other disorders, and insensitive and nonspecific diagnostic tests. While no cause has been definitely confirmed, there is increasing evidence that one or more infectious agents may cause the disease, although the organism may no longer be viable. Here we present 2 cases, in which sarcoidosis preceded tuberculosis and non-Hodgkin lymphoma. Development of new lesions in a patient with chronic/remitting sarcoidosis should be looked at with suspicion and promptly investigated in order to rule out an alternative/concomitant diagnosis. In such cases, tissue confirmation from the most accessible site, and bone marrow biopsy-if lymphoma is in the differential diagnosis-should be performed. In conclusion, we strongly advise that physicians be ready to reconsider the diagnosis of sarcoidosis in the presence of atypical manifestations or persistent/progressive disease despite conventional therapy.
2012
- The big clinical trials in idiopathic pulmonary fibrosis.
[Articolo su rivista]
Luppi, F; Spagnolo, Paolo; Cerri, Stefania; Richeldi, Luca
abstract
PURPOSE OF REVIEW:Since the late 1990 s, when a more uniform definition of idiopathic pulmonary fibrosis (IPF) was proposed, more than 3000 patients have been enrolled in clinical studies exploring novel therapies. Some of the most relevant trials have been published only recently.RECENT FINDINGS:This review describes and comments on the randomized clinical trials in IPF published within the past 18 months, with emphasis on the studies evaluating pirfenidone, which at present is the only drug approved for IPF (at least in Europe and Japan), and bosentan. This latter represents the largest single trial performed in IPF so far.SUMMARY:Despite multiple clinical trials, there is no strong, definitive evidence in favor of any agent to treat IPF. On the other hand, the placebo arms of these large trials have provided us with important critical information on the natural history of this disease. Clinical heterogeneity represents a critical issue to be taken into account in designing future clinical trials. The limited effectiveness of current treatment regimes has fuelled the search for a variety of new therapeutic approaches.
2012
- Use of Pirfenidone in Idiopathic Pulmonary Fibrosis: A Case Study
[Articolo su rivista]
Sgalla, Giacomo; Cerri, Stefania; Tonelli, Roberto; Cocconcelli, Elisabetta; Garuti, Martina; Ori, Margherita; Richeldi, Luca
abstract
Non disponibile
2011
- Emerging drugs for idiopathic pulmonary fibrosis.
[Articolo su rivista]
M., Selman; A., Pardo; Richeldi, Luca; Cerri, Stefania
abstract
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal lung disorder of unknown etiology. The disease is characterized by alveolar epithelial cell injury, formation of activated fibroblasts/myofibroblasts foci and finally by the exaggerated accumulation of extracellular matrix with the subsequent destruction of the lung architecture. The long-term survival is distinctly poor, with only a 20-30\% survival 5 years after the time of diagnosis. Actually, regardless of extensive research, no current therapy has been shown to either reverse or stop the progression of this disease. AREAS COVERED: The authors searched the Medline database from January 1990 to December 2010 using search terms 'pulmonary fibrosis', 'fibrosing alveolitis' and 'usual interstitial pneumonia'. Several subsets were included: definition and epidemiology, risk factors, clinical behavior, pathogenesis and therapy. For the section of IPF treatment, the authors examined all relevant studies including randomized controlled trials, cohort studies, case-control studies and cross-sectional studies. In this review, the authors describe the current therapeutic approaches, the ongoing clinical trials and some future options based on stem cells, lung bioengineering and microRNAs. EXPERT OPINION: The treatment of IPF represents one of the greatest challenges confronting respiratory medicine and, currently, there is no effective therapeutic option for IPF. Perhaps some of the drugs that are under evaluation in clinical trials will slow the decline of the pulmonary function tests or hopefully stabilize some patients. Nonetheless, it appears clear that new therapeutic approaches are urgently needed.
2011
- Genetic commonality between inflammatory bowel disease and sarcoidosis: the beginning of the end or the end of the beginning?
[Articolo su rivista]
Cerri, Stefania; du Bois, Rm; Spagnolo, Paolo
abstract
Crohn’s disease (CD) and ulcerative colitis, collectively
known as inflammatory bowel disease (IBD), and
sarcoidosis are multifactorial disorders thought to
result from complex interactions between environmental
stimuli (e.g. infectious agents), susceptibility genes (which
may predispose to the development of granulomatous inflammation) and modifier genes (which may affect disease
phenotype in people already susceptible). Neither IBD nor
sarcoidosis is the result of defects in a single major gene or
chemical pathway; instead, multiple genes, each contributing a relatively minor effect, are likely to be involved. In addition
to the granulomatous histopathology, both diseases share a
number of similarities in terms of ocular, dermatological and
joint manifestations, although sarcoidosis rarely involves the
gastrointestinal tract and IBD rarely involves the lung.
Immunological, bacteriological and genetic data support a link
between CD and sarcoidosis. Both disorders share a similar,
yet distinct, immune response, histologically defined by
non-caseating granulomas. Up to 50% of patients with CD
have been reported to test positive for Kveim antigens,
although these data are not replicated in all studies.
2011
- Role Of The QFT-IT Assay For The Diagnosis Of Latent Tuberculosis Infection Among Adult Immigrants
[Abstract in Rivista]
Losi, Monica; Dal Monte, Paola; Cagarelli, Roberto; Meacci, Marisa; DEL GIOVANE, Cinzia; Luppi, Fabrizio; Lombardi, Giulia; Spagnolo, Paolo; D'Amico, Roberto; Roversi, Pietro; Cerri, Stefania; Rumpianesi, Fabio; Fabbri, Leonardo; Richeldi, Luca
abstract
Background. Accurate identification and treatment of contacts with latent tuberculosis infection (LTBI) is a desirable goal to achieve effective tuberculosis (TB) control in areas with low prevalence of disease. In immigrants from high prevalence countries, especially in those who are close contacts of active TB cases, the low specificity of the tuberculin skin test (TST) represents an obstacle to the identification of truly infected BCG-vaccinated individuals. The Interferon-Gamma (IFN-g) Release Assays (IGRAs), based on M. tuberculosis
-specific antigens, might improve LTBI diagnosis in this population.
Methods. In a retrospective study, we assess the performance of the QuantiFERON-TB Gold In-Tube (QFT-IT, Cellestis Ltd., Victoria, Australia) assay and the TST in 84 adult immigrants from high prevalence countries: 68 (80.9%) of those individuals were close contacts of active TB cases.
Results. In 84 immigrants (mean age 37.7 ± 11.6 years, 46.3 % were males, 46.3% were BCG-vaccinated) TST was positive in 68 (80.9%) individuals: among these TST-positive individuals, 26 (38.2%) were negative with QFT-IT. QFT-IT assay tested positive in 44 (52.4%) subjects (TST vs QFT-IT: 80.9% vs 52.4%, p< 0.001). Two (2.4%) subjects tested QFT-IT-indeterminate and was TST-positive. Diagnostic overall agreement between TST and QFT-IT was 63.4% (k=0.23).
Conclusions. These preliminary data suggest that the rate of LTBI among adult immigrants from TB endemic countries, in our study most of them also close contacts of active TB cases, is significantly lower when detected by QFT-IT, than by TST. Moreover, our findings suggest that using an IGRA test for LTBI screening in this high risk population might reduce the number of candidates to preventive treatment and can provide potential substantial benefits for TB control.
2011
- Smoking-related interstitial lung disease
[Capitolo/Saggio]
Cerri, Stefania; Spagnolo, Paolo; F., Luppi; Richeldi, Luca
abstract
Cigarette smoking has a clear epidemiological association with lung diseases, characterised by chronic inflammation of both the bronchiolar and the interstitial lung compartments. There are several different smoking-related interstitial lung diseases, mainly desquamative interstitial pneumonia, respiratory bronchiolitis-
associated interstitial lung disease and pulmonary Langerhans’ cell histiocytosis.The epidemiology of such diseases is largely unknown, although the prevalence of cigarette smoking, particularly in low-income developing countries, indicates that smoking-induced interstitial lung disorders represent a high burden of disease worldwide. The role of chest high-resolution computed tomography has become increasingly important in differential diagnosis and follow-up. A new entity, the syndrome of combined pulmonary fibrosis and emphysema, emerged as another important smoking-related lung disorder with a poor prognosis, associated with the high prevalence of pulmonary hypertension. At the moment the role of anti-inflammatory and immunosuppressive treatment remains unclear, although in clinical practice most of these patients will receive at least one course of corticosteroid therapy. It is vital to stress the importance of identifying these patients and helping them quit smoking.
2010
- Human mucosal associated invariant T cells detect bacterially infected cells
[Articolo su rivista]
Gold, Marielle C.; Cerri, Stefania; Smyk Pearson, Susan; Cansler, Meghan E.; Vogt, Todd M.; Delepine, Jacob; Winata, Ervina; Swarbrick, Gwendolyn M.; Chua, Wei Jen; Yu, Yik Y. L.; Lantz, Olivier; Cook, Matthew S.; Null, Megan D.; Jacoby, David B.; Harriff, Melanie J.; Lewinsohn, Deborah A.; Hansen, Ted H.; Lewinsohn, David M.
abstract
Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtbuninfected individuals. Interestingly, these Mtb-reactive cells expressed the Va7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. © 2010 Gold et al.
2010
- Non-steroid agents for idiopathic pulmonary fibrosis
[Articolo su rivista]
Spagnolo, Paolo; Del Giovane, C.; Luppi, F.; Cerri, Stefania; Balduzzi, Sara; Walters, Eh; D'Amico, Roberto; Richeldi, Luca
abstract
BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor outcome and no effective treatment to date. This is an update of a Cochrane Review first published in 2003.OBJECTIVES: To assess the efficacy of non-steroid agents in adults with idiopathic pulmonary fibrosis.SEARCH STRATEGY: We searched the Cochrane Airways Group Register (30 March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2010), Ovid MEDLINE to March week 5, 2010, EMBASE to week 13, 2010 and PubMed to April 2010, with additional handsearching, including abstracts of international conferences. We also contacted pharmaceutical companies and researchers in the field.SELECTION CRITERIA: Randomised studies comparing non-steroid drugs with placebo or steroids in adults with idiopathic pulmonary fibrosis.DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, extracted data and assessed risk of bias. We contacted pharmaceutical companies to obtain missing information, if any. We combined survival outcomes using Peto odds ratios or hazard ratios (HR).MAIN RESULTS: Fifteen trials involving 10 different drugs were included. Two trials enrolling 1156 patients compared interferon gamma-1beta with placebo: interferon gamma-1beta did not significantly improve survival (HR 0.88, 95% CI 0.47 to 1.64; P = 0.68). Four trials involving 1155 patients compared pirfenidone with placebo. Three trials, conducted in 1046 patients, provided data on progression-free survival: pirfenidone significantly reduced the risk of disease progression by 30% (HR 0.70, 95% CI 0.56 to 0.88, P = 0.002). Data on the effect of pirfenidone on pulmonary function could only be assessed for two studies analysing 314 patients. Forced vital capacity or vital capacity was significantly improved by pirfenidone (mean difference 0.08 L, 95% CI 0.03 to 0.13, P = 0.0006).AUTHORS' CONCLUSIONS: Based on available data, partly still unpublished, pirfenidone appears to improve progression-free survival and, to a lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis. More data are needed on overall survival and quality of life on treatment. From the studies in this review, interferon gamma-1beta has not been shown to affect survival. Other agents evaluated in single studies either failed to provide evidence for a benefit or need to be assessed in larger randomised controlled trials.
2009
- Human IL-10 Producing T Cells Specific for Mycobacterium tuberculosis.
[Abstract in Rivista]
Cerri, Stefania; Gold, Marielle; Jin, Justin; Robinson, T; Thompson, Scott; Smyk Pearson, Sue; Lewinsohn, Deborah A; Lewinsohn, David M.
abstract
IL−10 producing Mtb−specific CD4+ T cells can be detected in pulmonary TB patients with persistent anergy. Aim of the study was to define the spectrum of ex vivo frequencies of IL−10 producing Mtb−specific CD4+ and CD8+ T cells in adults. Peripheral blood mononuclear cells were collected from uninfected adults and subjects with latent tuberculosis infection or active tuberculosis. Monocyte−derived dendritic cells (DC) were infected overnight with Mtb (MOI=50:1) and incubated with different concentrations of positively selected autologous CD4+ and CD8+ T cells in an IL−10 ELISPOT assay. In all subjects we detected additional IL−10 producing cells with the addition of T cells to Mtb−infected DC, compared to Mtb−infected DC alone. We next focused on CD8+ T cells and asked if they represent the additional IL−10 producing cells. Autologous DC were left uninfected or infected with Mtb (MOI=20:1). After overnight incubation, positively selected CD8+ T cells were added and incubated overnight. Then, CD8+ T cells were positively selected from these cultures using magnetic beads, and RNA was isolated and subjected to RT−PCR. Relative quantitation of IL−10 RNA showed that CD8+ T cells were induced to produce IL−10 in response to Mtb−infected DC, suggesting that T cells are a source of the augmented IL−10 production previously seen in co−cultures of Mtb−infected DC with T cells. We next sought to isolate IL−10 producing Mtb−specific CD8+ T cells using a limiting dilution T cell cloning approach. T cells from wells exhibiting growth were analyzed by ELISPOT for their production of IFN−g and/or IL−10 in
response to Mtb−infected autologous DC. In all donors, IFN−g producing CD8+ T cells were most frequently isolated. Most donors also had IL−10 producing CD8+ T cells, the majority of which also produced IFN−g. Finally, we confirmed that IL−10 has the potential to inhibit IFN−g CD4+ T cell responses to Mtb antigens.
2009
- Performance of tests for latent tuberculosis in different groups of immunocompromised patients.
[Articolo su rivista]
Richeldi, Luca; Losi, M; D'Amico, Roberto; Luppi, M; Ferrari, A; Mussini, Cristina; Codeluppi, M; Cocchi, S; Prati, F; Paci, V; Meacci, M; Meccugni, B; Rumpianesi, F; Roversi, P; Cerri, Stefania; Luppi, F; Ferrara, G; Latorre, I; Gerunda, Giorgio Enrico; Torelli, G; Esposito, R; Fabbri, Leonardo
abstract
BACKGROUND: Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their managementis hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB(TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy forlatent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown.METHODS AND RESULTS: Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneouslyperformed, their results were compared, and intertest agreement was evaluated.Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p <0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (kappa = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (kappa = 0.16) orQFT-IT (kappa = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001).CONCLUSIONS: Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based onthese results, we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.
2008
- Using ELISpot technology to improve the diagnosis of tuberculosis infection: from the bench to the T-SPOT.TB assay
[Articolo su rivista]
Richeldi, Luca; Losi, M; Cerri, Stefania; Casali, L; Fabbri, Lm; Ferrara, G.
abstract
Accurate detection and adequate treatment of latent tuberculosis infection represent a fundamental cornerstone to reduce the incidence of tuberculosis, in particular in low-incidence countries and among high-risk (i.e., immunosuppressed) individuals. Until recently, however, only the century-old tuberculin skin test was available as a diagnostic tool; its poor specificity and low sensitivity among immunosuppressed individuals has been a major limit to the implementation of effective tuberculosis control strategies. In the last years, the achievements of basic research on the genetics and immunology of Mycobacterium tuberculosis infection rapidly translated into clinical practice two elements of the vast amounts of knowledge acquired. First, the identification and use of specific antigens, which are absent in the tuberculosis vaccine and in most nontuberculous mycobacteria; and second, the identification of IFN-gamma as the main fundamental cytokine implicated in the effective immune response against M. tuberculosis. In an incredibly powerful combination, this new knowledge has been applied to enzyme-linked immunospot (ELISpot) technology, the most sensitive technique to quantify an in vitro antigen-specific cellular immune response. In only a few years, a new commercial, regulatory-approved, diagnostic assay has entered clinical practice as a substitute to the tuberculin skin test. The T-SPOT.TB test has already been applied to several hundreds of patients in the context of controlled clinical trials in different countries and prevalence areas, showing improved specificity and sensitivity in the diagnosis of latent tuberculosis infection over the skin test, in particular in those settings where the diagnosis is most needed.
2007
- Impact of a T cell-based blood test for tuberculosis infection on clinical decision-making in routine practice
[Articolo su rivista]
S., Gooding; O., Chowdhury; T., Hinks; Richeldi, Luca; M., Losi; K., Ewer; K., Millington; R., Gunatheesan; Cerri, Stefania; J., Mcnally; A., Lalvani
abstract
New T cell-based blood tests for tuberculosis infection could improve diagnosis of tuberculosis but their clinical utility remains unknown. We describe the role of the ELISpot test in the diagnostic work-up of 13 patients presenting with suspected tuberculosis in routine practice. Of the seven patients with a final diagnosis of active tuberculosis, all were positive by ELISpot including three with false-negative tuberculin skin test results. Rapid determination of tuberculosis infection by ELISpot accelerated the diagnosis of tuberculosis, enabling early treatment initiation.
2007
- Rifabutin for treating pulmonary tuberculosis.
[Articolo su rivista]
G., Davies; Cerri, Stefania; Richeldi, Luca
abstract
BACKGROUND:Rifamycins are an essential component of modern short-course regimens for treating tuberculosis. Rifabutin has favourable pharmacokinetic and pharmacodynamic properties and is less prone to drug-drug interactions than rifampicin. It could contribute to shortening of therapy or simplify treatment in HIV-positive people who also need antiretroviral drugs.OBJECTIVES:To compare combination drug regimens containing rifabutin with those containing rifampicin for treating pulmonary tuberculosisSEARCH STRATEGY:We searched Cochrane Infectious Diseases Group Specialized Register (January 2007), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (1966 to January 2007), EMBASE (1974 to January 2007), and LILACS (1982 to January 2007). We also searched the Indian Journal of Tuberculosis (1983 to 2006), conference abstracts, reference lists, and unpublished data on file at Pfizer Inc.SELECTION CRITERIA:Randomized and quasi-randomized trials including participants with sputum smear and/or culture-confirmed tuberculosis that compared a rifabutin-containing with an otherwise identical rifampicin-containing regimen.DATA COLLECTION AND ANALYSIS:Two authors independently assessed study eligibility and methodological quality, and extracted data. Dichotomous data were analysed and combined using relative risks (RR) with 95% confidence intervals (CI) using a fixed-effect model. Subgroup analyses were carried out according to rifabutin dose.MAIN RESULTS:Five trials with a total of 924 participants met the inclusion criteria; 5% of participants were HIV positive. Only one small trial was methodologically adequate. The two largest trials (818 participants) had unclear allocation concealment and included < 90% of randomized participants in the analysis. There was no statistically significant difference in between the regimens for cure (RR 1.00, 95% CI 0.96 to 1.04; 553 participants, 2 trials) or relapse (RR 1.23, 95% CI 0.45 to 3.35; 448 participants, 2 trials). The number of adverse events was not significantly different (RR 1.42, 95% CI 0.88 to 2.31; 714 participants, 3 trials), though the RR increased with rifabutin dose: 150 mg (RR 0.98, 95% CI 0.45 to 2.12; 264 participants, 2 trials); and 300 mg (RR 1.78, 95% CI 0.94 to 3.34; 450 participants, 2 trials). However, lack of dose adjustment by weight in the relevant trials complicates interpretation of this relationship.AUTHORS' CONCLUSIONS:The replacement of rifampicin by rifabutin for first-line treatment of tuberculosis is not supported by the current evidence. HIV-positive people with tuberculosis, the group most likely to benefit from the rifabutin use, are under-represented in trials to date, and further trials in this group would be useful.
2006
- Diagnosis of occult tuberculosis in hematological malignancy by enumeration of antigen-specific T cells.
[Articolo su rivista]
Richeldi, Luca; Luppi, Mario; Losi, Monica; Luppi, Fabrizio; Potenza, Leonardo; Roversi, P; Cerri, Stefania; Millington, Ka; Ewer, K; Fabbri, Leonardo; Torelli, Giuseppe; Lalvani, A.
abstract
n.d.
2005
- Comparison of the tubercolin skin test and the ellispot blood test for the diagnosis of latent tuberculosis infection in pre-transplant dialysis patients
[Abstract in Atti di Convegno]
Di Felice, A; Losi, Monica; Roversi, P; Cerri, Stefania; Debbi, Alberto; Ferrari, Federica; Ferramosca, Emiliana; Millington, K; Cappelli, Gianni; Albertazzi, Alberto; Fabbri, Leonardo; Lalvani, A; Richeldi, Luca
abstract
End stage renal disease (ESRD) is a known risk factor for progression to active tuberculosis (TB) from latent tuberculosis infection (LTBI). Kidney transplant and immunosuppressive therapy may increase the risk of TB recurrence. Patients with LTBI undergoing dialysis would therefore benefit from preventive treatment with isoniazid, which often has adverse side effects in this particular group of patients. Therefore it is important to accurately identify ESRD patients with LTBI, mainly if awaiting renal transplantation. The standard tool for diagnosing LTBI is the century-old tuberculin skin test (TST); however, patients with ESRD, as many other immunosuppressedpatients, often have falsely negative TST results. The Enzyme-Linked ImmunoSpot (ELISPOT) test is a new test which enumerates M. tuberculosis-specific T-cells in peripheral blood samples and has been already shown to be more specific and more sensitive than the TST for diagnosis of LTBI. We tested 84 ESRD patients on dialysis treatment with TST and ELISPOT: 26 were on peritoneal dialysis and 57 on hemodialysis; only 1 patient was on conservative treatment. Mean age was 48±14 years (range 23-75); 51 male and 33 female. Simultaneous RD1 Elispot and TST (5 UI PPD) were performed. According to current guidelines, the cut-off value for a positive TST using 5 UI of PPD is 10 mm; based upon previously published studies, the pre- defined positive cut-off for the ELISPOT is 20 spot forming cells per million peripheral blood mononuclear cells. In 64 patients (76%) TST and ELISPOT gave concordant results and in more than 90% were both negative. Only 2 patients tested TST-positive and ELISPOT-negative (one was an immigrant from a high-prevalence Country) while 18 (21%) were TST-negative, but ELISPOT positive. These preliminary results indicate that a significant proportion of ESRD patients on dialysis treatment may have hitherto unrecognised LTBI and an associated increased risk of progression to active disease, mainly after renal transplantation.
2005
- Empoyment of the ELISPOT blood test for the diagnosis of latent tuberculosis infection in dialysis patients awaiting renal transplantation
[Abstract in Rivista]
Di Felice, A; Losi, Monica; Roversi, P; Cerri, Stefania; Debbi, A; Ferrari, F; Ferramosca, E; Ravera, F; Millington, K; Cappelli, Gianni; Lucchi, L; Albertazzi, Alberto; Fabbri, Leonardo; Lalvani, A; Richeldi, L.
abstract
Abstract COngresso Internazionale
2005
- Steroid and/or other immunosuppressive therapies in idiopathic interstitial pneumonias: have they still a role?
[Articolo su rivista]
Luppi, F; Cerri, Stefania; Richeldi, Luca
abstract
The idiopathic interstitial pneumonias (IIPs) comprise a number of clinico-pathological entities of unknown origin, which are sufficiently different from one another to be designated as separate disease entities. The aim of this review is to describe the level of evidence available on the efficacy of corticosteroids and immunosuppressive, antifibrotic, or immunomodulatory therapies in the treatment of different IIPs.
2005
- Tubercolosi: Nuove opportunità per controllare una vecchia malattia?
[Articolo su rivista]
Ferrara, Giovanni; Cerri, Stefania; Fabbri, Leonardo; Richeldi, Luca
abstract
After the mention of traditional laboratory pathways historically (and still presently) followed for the diagnosis of tuberculosis, the most recent changes to such traditional methods are taken into consideration. The contribution of the microscopic examination with its pros and cons, the bacterial cultures and the advantages deriving from the last generation mediums, the (growing in importance) diagnosis of bacterial resistances and, last not least, the most recent technologies in the field of molecular diagnosis, from polymerase chain reaction to the use of nucleic acid probes, from the molecular typisation of the mycobacterium to the genotypic methods to test antitubercular drug resistances. Particular attention has been put on novel immunologic tests, perhaps yet to be perfectioned but already important and to be considered in the present panel of diagnostic tools, mainly for their relevance in the diagnosis of latent tuberculosis: in this sense both such tests, QuantiFERON-TB GOLD as well as T SPOT-TB (based on the interferon gamma identification) are discussed and compared with the classic Mantoux intradermoreaction.
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
- Therapeutic approaches to idiopathic pulmonary fibrosis
[Articolo su rivista]
Luppi, Fabrizio; Cerri, Stefania; DE CARLO, Maria Rosaria; Serini, Roberto; 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. Based upon the methodologies of the systematic reviews of the Cochrane collaboration, this article describes the available evidence for the therapy of IPF. Good-quality studies on oral corticosteroids, the most commonly used medical therapy 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, γ interferon, showed a significant effect in a first small randomized study, but its effect on survival has not been confirmed in a larger randomized, controlled trial. Preliminary positive data on high doses N-acetylcysteine have also been reported. 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 using gamma interferon and/or other immunomodulatory agents.