1,585 results on '"Settore MED/10 - Malattie dell'Apparato Respiratorio"'
Search Results
2. BI 1015550: an investigational phosphodiesterase 4B (PDE4B) inhibitor for lung function decline in idiopathic pulmonary fibrosis (IPF)
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Giacomo Sgalla, Jacopo Simonetti, Stefania Cortese, and Luca Richeldi
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Pharmacology ,BI 1015550 ,lung fibrosis ,Pharmacology (medical) ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,General Medicine ,PDE4 ,idiopathic pulmonary fibrosis - Published
- 2023
3. Prevalence, trends and outcomes of long-term inhaled antibiotic treatment in people with cystic fibrosis without chronic Pseudomonas aeruginosa infection – A European cystic fibrosis patient registry data analysis
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Annalisa Orenti, Meir Mei-Zahav, Patrizia Boracchi, Anders Lindblad, and Michal Shteinberg
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Pulmonary and Respiratory Medicine ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Pediatrics, Perinatology and Child Health ,Settore MED/01 - Statistica Medica - Abstract
Long-term treatment with inhaled antibiotics is recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (PA). However, pwCF without chronic PA infection are also commonly treated with inhaled antibiotics. Using data from the European Cystic Fibrosis Patient Registry (ECFSPR) we aimed to determine the prevalence and factors associated with inhaled antibiotic treatment in pwCF without chronic PA infection, and long-term outcomes with inhaled antibiotics use.The ECFSPR was searched for pwCF 6 years of age and older who were not chronically infected with PA at baseline. Factors associated with inhaled antibiotic use were first assessed through a logistic regression. From this model a propensity score was computed for each individual, providing the likelihood of being treated with inhaled antibiotics. Long-term outcomes with and without inhaled antibiotics were assessed separately for propensity scores tertiles.7210 pwCF without chronic PA infection at baseline were included, with 2722 (37.75%) receiving long-term treatment with inhaled antibiotics. Treatment with inhaled antibiotics was more prevalent with severe genotype, diabetes, pancreatic insufficiency, and past infection with chronic PA (OR 3.8, 95% CI, 2.88-5.04). Treatment with inhaled antibiotics was not associated with a reduced risk for acquisition of PA or other resistant pathogens, or with improved lung function decline, mortality, or transplantation.Many pwCF without chronic PA infection are receiving long-term treatment with inhaled antibiotics despite lack of support from clinical trials or practice guidelines. We did not observe improve outcomes with inhaled antibiotics. Our findings suggest controlled studies evaluating specific inhaled antibiotic regimens targeting specific pathogens or indications be performed to determine their effect.
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- 2023
4. Peripheral Airway Sarcoidosis: Seeing What Was Previously Invisible
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No abstract available
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- 2023
5. An up-to-date review of approved and emerging antibody therapies for idiopathic pulmonary fibrosis
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Introduction The use of pirfenidone and nintedanib in treating Idiopathic Pulmonary Fibrosis (IPF) has shown significant slowing down of the progressive functional decline in these patients. In recent times, antibody-based therapies with precise molecular targets have also been explored as alternative treatments to IPF. Areas covered This review aims to summarize the available updates regarding monoclonal antibodies that have been tested in IPF. The drugs describedare developed to antagonize inflammation,immunity pathways and fibrogenesis. Currently, the anti-CTGF pamrevlumab has demonstrated a significant reduction in functional decline as compared to placebo and is undergoing the last stages of phase 3 trial. Expert opinion Although antibody-based therapies for IPF have had unsatisfactory results in most trials in the last few years, the pursuit of therapeutic development in this field should continue to deliver a more personalized treatment approach in the future, which is currently not available with existing treatment options. However, several molecules are still under study and some have shown encouraging results in the early phases of clinical trials. Future investigations need to be more carefully designed and valid predictive markers of response to treatment should be used to enhance the effectiveness of future trials.
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- 2023
6. The Impact of Telemedicine during Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic and Future Perspectives: A Systematic Review
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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide since December 2019, causing the COVID-19 pandemic. Several measures have taken place in many countries to avoid further spread of the virus and to manage infected people according to disease severity. Notably, telemedicine (TM) was successfully used to manage less severe patients. Our aim was to assess the impact and the edges of using TM in home-isolated or hospitalized patients affected by SARS-CoV-2 infection and its further application. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, focusing on randomized controlled trials (RCTs) published in English and available on PubMed database. Full texts were blindly reviewed and then assessed according to PICO model. Results: Our research identified a total of 1,959 records, of which 24 were potentially eligible through the articles full-text review. Six papers were included for data extraction and 18 articles were excluded: 10 articles were not RCTs and 8 articles did not involve SARS-CoV-2 patients. The TM application showed an improvement in psychological stress, mental disorders, and a significant reduction of general stress in patients affected by SARS-CoV-2 infection. The effectiveness of using TM in rehabilitative respiratory programs has been also reported. Furthermore, the benefits of TM application in tailored monitoring of vital parameters in home-isolated patients helped clinicians to early identify a deterioration of clinical conditions. Conclusion: The use of TM during COVID-19 pandemic represented a novel, intriguing, versatile, and useful tool to support clinical practice. This evidence suggests considering TM in a wider range of clinical applications.
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- 2023
7. Approach to Clinical Trials for the Prevention of Pulmonary Fibrosis
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NO
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- 2023
8. Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF)
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Introduction There is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in a phase II study in patients with IPF. This study design describes the subsequent pivotal phase III study of BI 1015550 in patients with IPF (FIBRONEER-IPF).Methods and analysis In this placebo-controlled, double-blind, phase III trial, patients are being randomised in a 1:1:1 ratio to receive 9 mg or 18 mg of BI 1015550 or placebo two times per day over at least 52 weeks, stratified by use of background antifibrotics (nintedanib/pirfenidone vs neither). The primary endpoint is the absolute change in FVC at week 52. The key secondary endpoint is a composite of time to first acute IPF exacerbation, hospitalisation due to respiratory cause or death over the duration of the trial.Ethics and dissemination The trial is being carried out in compliance with the ethical principles of the Declaration of Helsinki, in accordance with the International Council on Harmonisation Guideline for Good Clinical Practice and other local ethics committees. The results of the study will be disseminated at scientific congresses and in peer-reviewed publications.
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- 2023
9. A randomized trial of pamrevlumab in patients with COVID-19 pneumonia
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- 2023
10. Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study
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BackgroundSmall airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored.MethodsWe conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment.ResultsCTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 +/- 18.3 vs. 80.0 +/- 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 +/- 19.7 vs. 63.8 +/- 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 +/- 1.53, p < 0.001 in patients with SAD; 5.13 +/- 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters.ConclusionIn our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.
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- 2023
11. BI 1015550: an investigational phosphodiesterase 4B (PDE4B) inhibitor for lung function decline in idiopathic pulmonary fibrosis (IPF)
- Abstract
IntroductionThe two available therapies for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, slow down but do not halt IPF progression. Therefore, several agents with specific molecular targets have been recently investigated to find a cure for IPF. Phosphodiesterase 4 (PDE4) inhibition is known for its anti-inflammatory and antifibrotic properties. BI 1015550, an oral preferential inhibitor of the isoform PDE4B, could express complementary activity to current therapies in IPF and other forms of progressive pulmonary fibrosis.Areas coveredIn this review, we first provide an overview toof the current IPF treatment market, followed by the description of pharmacokinetics and pharmacodynamics of BI 1015550. The main preclinical and early clinical evidence on BI 1015550 is then described, as well as its potential as an IPF treatment.Expert opinionOral treatment with BI 1015550 was shown to stabilize lung function as compared to placebo over 12 weeks, both among patients with and without background antifibrotic use, with an acceptable safety profile in a phase 2 trial, and a phase 3 trial has been initiated. To date, this represents to date the largest effect size for an IPF investigational drug tested in a phase 2 trial with the shortest duration.
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- 2023
12. Challenges in the diagnosis of idiopathic pulmonary fibrosis: the importance of a multidisciplinary approach
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Introduction: The diagnosis of Idiopathic pulmonary fibrosis (IPF) requires the careful exclusion of secondary causes of interstitial lung disease (ILD), and the collaboration among different specialists is considered paramount to establish a diagnosis with high diagnostic confidence. The multidisciplinary discussion (MDD) has assumed an increasing importance over the years in the different phases of the IPF diagnostic work-up. Areas covered: The role of MDD in the diagnosis and management of IPF will be described. Practical insights will be provided into how and when to perform MDD based on the available scientific evidence. Current limitations and future perspectives will be discussed. Expert opinion: In the absence of high diagnostic confidence, agreement between different specialists during MDD is recognized as a surrogate indicator of diagnostic accuracy. Often, despite a lengthy evaluation, the diagnosis remains unclassifiable in a significant percentage of patients. MDD therefore appears to be pivotal in attaining an accurate diagnosis of ILDs. The discussion among different specialists can also include other specialists, such as rheumatologists and thoracic surgeons, in addition to the core group of pulmonologists, radiologists, and pathologists. Such discussions can allow greater diagnostic accuracy and have important effects on management, pharmacologic therapies, and prognosis.
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- 2023
13. Idiopathic Pulmonary Fibrosis: State of the Art for 2023
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Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterized by worsening respiratory symptoms and physiologic impairment. Increasing awareness of the clinical manifestations of IPF, more widespread use of computed tomography scans, and other potential factors have contributed to a rising prevalence of IPF over the last two decades, especially among people over the age of 65. Significant advances in the understanding of the pathobiology of IPF have emerged, and multiple genetic and nongenetic contributors have been identified. The individual patient course and the rate of disease progression in IPF are often unpredictable and heterogeneous. The rate of lung function decline is further modified by treatment with antifibrotic therapies, which have been shown to slow down disease progression. The presence of comorbid conditions may increase symptom burden and impact survival. Clinical monitoring at regular intervals to assess for disease progression by worsening symptoms, physiologic parameters, and/or radiological features is essential to assess the natural disease course, and to guide further management, including prompt detection of complications and comorbid conditions that warrant additional treatment considerations, and timely consideration of referral to palliative care and lung transplantation for the appropriate patient. More studies are needed to determine whether early detection of IPF might improve patient outcomes. The purpose of this concise clinical review is to provide an update on IPF diagnosis, epidemiology, natural history and treatment in the context of new knowledge and latest clinical practice guidelines.
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- 2023
14. Predictors of Stability/Improvement of Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis After One Year of Treatment With Nintedanib
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- 2023
15. Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials
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Importance: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective: To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, setting, and participants: The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions: Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main outcomes and measures: The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George's Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results: At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was -124.6 mL (95% CI
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- 2023
16. Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants
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Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and main results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
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- 2023
17. Reply to: Cottin et al., Johannson et al., Scholand and Wells, and Crowley et al
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- 2023
18. The Future of Clinical Trials in Idiopathic Pulmonary Fibrosis
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- 2023
19. Treatable traits in interstitial lung diseases: a call to action
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- 2023
20. Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm3: A Post Hoc Analysis from the ANANKE Study
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Gianenrico Senna, Maria Aliani, Elena Altieri, Pietro Bracciale, Luisa Brussino, Maria Filomena Caiaffa, Paolo Cameli, Giorgio Walter Canonica, Cristiano Caruso, Maria D'Amato, Fausto De Michele, Stefano Del Giacco, Fabiano Di Marco, Francesco Menzella, Girolamo Pelaia, Paola Rogliani, Micaela Romagnoli, Pietro Schino, Jan Walter Schroeder, Alessandra Vultaggio, Sara Rizzoli, Alessandro Zullo, Silvia Boarino, Marilena Palmisano, Alessandra Rossi, Gianfranco Vitiello, and Stefano Centanni
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Pulmonary and Respiratory Medicine ,benralizumab ,blood eosinophil count ,observational ,real-life ,real-world evidence ,severe eosinophilic asthma ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Settore MED/10 ,Journal of Asthma and Allergy ,Immunology and Allergy - Abstract
Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria DâAmato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie âFederico IIâ, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale âS. Valentinoâ, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital âTor Vergataâ, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome âTor Vergataâ, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico âF. Miulliâ, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300â 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300â 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300â 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300â 450 subset showed similar reductions in AER (â 94.8% vs â 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300â 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300â 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life
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- 2022
21. A Phase IIb Randomized Clinical Study of an Anti-αvβ6 Monoclonal Antibody in Idiopathic Pulmonary Fibrosis
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Ganesh Raghu, Majd Mouded, Daniel C. Chambers, Fernando J. Martinez, Luca Richeldi, Lisa H. Lancaster, Mark J. Hamblin, Kevin F. Gibson, Ivan O. Rosas, Antje Prasse, Guolin Zhao, Michael Serenko, Natasha Novikov, Amy McCurley, Prashant Bansal, Christopher Stebbins, Million Arefayene, Stella Ibebunjo, Shelia M. Violette, Diana Gallagher, and Jürgen Behr
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safety ,Pulmonary and Respiratory Medicine ,Antibodies, Monoclonal ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,anti-αvβ6 IgG1 monoclonal antibody ,idiopathic pulmonary fibrosis ,randomized clinical trial ,Critical Care and Intensive Care Medicine ,Antibodies ,Treatment Outcome ,treatment efficacy ,Double-Blind Method ,Immunoglobulin G ,Monoclonal ,Humans - Published
- 2022
22. Nontuberculous mycobacteria infection and pulmonary disease in bronchiectasis
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Kseniia Suska, Francesco Amati, Giovanni Sotgiu, Andrea Gramegna, Marco Mantero, Margherita Ori, Maurizio Ferrarese, Luigi Ruffo Codecasa, Anna Stainer, Francesco Blasi, and Stefano Aliberti
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Pulmonary and Respiratory Medicine ,Settore MED/10 - Malattie dell'Apparato Respiratorio - Abstract
BackgroundAlthough interest in nontuberculous mycobacteria (NTM) infection has increased in the last decades, published data vary according to different geographical areas, diagnostic facilities and quality of study design. This study aims at assessing both prevalence and incidence of NTM infection and NTM pulmonary disease (NTM-PD) among adults with bronchiectasis, to describe patients’ characteristics, therapeutic options and clinical outcomes.MethodsBronchiectasis adults who had been tested for NTM were enrolled at the Bronchiectasis Program of the Policlinico Hospital in Milan, Italy, from 2016 to 2018.ResultsAmong the 373 patients enrolled, 26.1% had at least one respiratory sample positive for NTM and 12.6% reached a diagnosis of NTM-PD. Incidence rates for NTM infection and NTM-PD were 13 (95% CI 10–16) and 4 (95% CI 2–6) per 100 person-years, respectively. The most prevalent NTM species causing NTM-PD wereM. intracellulare(38.3%),M. avium(34.0%),M. abscessus(8.5%) andM. kansasii(8.5%). Once treatment for NTM-PD was initiated, a favourable outcome was documented in 52.2% of the patients, while a negative outcome was recorded in 32.6%, including recurrence (17.4%), treatment failure (10.9%), re-infection (2.2%) and relapse (2.2%). Treatment halted was experienced in 11 (23.9%) patients.ConclusionsNTM infection is frequent in bronchiectasis patients and the presence of NTM-PD is relevant. The low success rate of NTM-PD treatment in bronchiectasis patients requires a call to action to identify new treatment modalities and new drugs to improve patients’ outcomes.
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- 2022
23. Long-term outcomes of combination biologic therapy in uncontrolled severe asthma: a case study
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Andrea, Baccelli, Marcelina, Koćwin, Elena M, Parazzini, Rocco F, Rinaldo, and Stefano, Centanni
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Pulmonary and Respiratory Medicine ,Severe asthma ,allergic asthma ,biologic therapy ,eosinophilic asthma ,uncontrolled asthma ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Pediatrics, Perinatology and Child Health ,Immunology and Allergy - Abstract
Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies.Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019.The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic.Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.
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- 2022
24. Cardiopulmonary testing in adult patients with β-thalassemia major in comparison to healthy subjects
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G. Piatti, M. Giuditta, D. Consonni, E. Cassinerio, and M. D. Cappellini
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Adult ,Exercise Tolerance ,Settore MED/09 - Medicina Interna ,Cardiopulmonary test ,Exercise capacity ,Iron overload ,Muscular deconditioning ,β-Thalassemia ,Iron ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,beta-Thalassemia ,Hematology ,General Medicine ,Healthy Volunteers ,Oxygen ,Oxygen Consumption ,Exercise Test ,Quality of Life ,Humans - Abstract
β-Thalassemia patients often have a reduced capacity of exercise and abnormal respiratory function parameters, but the reasons are unclear. In order to identify the causes of the exercise limitation, we performed a cardiopulmonary exercise testing (CPET) in a group of 54 adult β-thalassemia major (TM) patients without pulmonary arterial hypertension and in a group of healthy control subjects. All subjects underwent cardiac echocardiography and carried out pulmonary function tests. TM patients also filled an IPAQ questionnaire on usual physical activity (PA).Overall, TM patients have a diminished exercise performance in comparison to control subjects. In fact, peak oxygen uptake (V’O2 peak), expressing maximum exercise capacity, was decreased in 81.5% of the patients; similarly, anaerobic threshold (V’O2@AT) and O2 pulse also resulted lowered. In multivariable regression models adjusted for gender, age, BMI, and mean haemoglobin, V’O2 peak and O2 pulse were positively associated with cardiac iron overload (T2*). No ventilatory limitation to exercise was observed. The most important causes of exercise limitation in these patients were muscular deconditioning and reduced cardiac inotropism due to iron deposition. Only 15/54 (27.8%) TM patients used to perform vigorous physical activity. These results suggest that a program of regular physical activity may be useful to increase the tolerance to effort and therefore to improve the quality of life in these patients.
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- 2022
25. Reticulation Is a Risk Factor of Progressive Subpleural Nonfibrotic Interstitial Lung Abnormalities
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Yuchen Zhang, Huajing Wan, Luca Richeldi, Min Zhu, Yan Huang, Xiaofeng Xiong, Junzhe Liao, Wenjun Zhu, Lingli Mao, Linrui Xu, Dongfan Ye, Ling Chen, Jia Liu, Linxi Fu, Liangyuan Li, Lan Lan, Ping Li, Lixia Wang, Xiaoju Tang, and Fengming Luo
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Pulmonary and Respiratory Medicine ,Risk Factors ,Humans ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Respiratory System Abnormalities ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,Critical Care and Intensive Care Medicine ,Lung ,Progressive Subpleural non-Fibrotic Interstitial Lung Abnormalities - Published
- 2022
26. Proprietà meccaniche e comportamento elastico del polmone affetto da fibrosi con pattern 'polmonite interstiziale tipica' in corso di ventilazione meccanica: sviluppo e significato clinico della teoria del polmone 'squishy ball'
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Tonelli, Roberto
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Fibrosi polmonare ,Meccanica polmonare ,Ventilazione ,Stress ,Deformazione ,Lung fibrosis ,Lung mechanics ,Ventilation ,Strain ,Settore MED/10 - Malattie dell'Apparato Respiratorio - Published
- 2023
27. L'interazione tra endoscopisti e clinici: significato clinico e risultati della valutazione multimodale e trattamento di malattie benigne e maligne delle vie aeree
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Andrisani, Dario
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ostruzione vie aeree ,stenosi benigne ,approcciomultimodale ,airway obstructions ,benign stenosis ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,gestione endoscopica ,neoplasie vie aeree ,endoscopicmanagement ,multi-modal approach ,malign airwaydisease - Published
- 2023
28. Interventional pulmonology techniques in lung transplantation
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Michele Mondoni, Rocco Francesco Rinaldo, Paolo Solidoro, Fabiano Di Marco, Filippo Patrucco, Stefano Pavesi, Andrea Baccelli, Paolo Carlucci, Dejan Radovanovic, Pierachille Santus, Federico Raimondi, Sergio Vedovati, Letizia Corinna Morlacchi, Francesco Blasi, Giovanni Sotgiu, and Stefano Centanni
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Pulmonary and Respiratory Medicine ,BAL ,Lung transplantation ,Transbronchial biopsy ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Bronchoscopy ,Chronic lung allograft disease ,Acute cellular rejection ,Cryobiopsy - Published
- 2023
29. Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study
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Marchetti, Pierpaolo, Miotti, Jessica, Locatelli, Francesca, Antonicelli, Leonardo, Baldacci, Sandra, Battaglia, Salvatore, Bono, Roberto, Corsico, Angelo, Gariazzo, Claudio, Maio, Sara, Murgia, Nicola, Pirina, Pietro, Silibello, Camillo, Stafoggia, Massimo, Torroni, Lorena, Viegi, Giovanni, Verlato, Giuseppe, Marcon, Alessandro, the BIGEPI Group, Marchetti, Pierpaolo, Miotti, Jessica, Locatelli, Francesca, Antonicelli, Leonardo, Baldacci, Sandra, Battaglia, Salvatore, Bono, Roberto, Corsico, Angelo, Gariazzo, Claudio, Maio, Sara, Murgia, Nicola, Pirina, Pietro, Silibello, Camillo, Stafoggia, Massimo, Torroni, Lorena, Viegi, Giovanni, Verlato, Giuseppe, and Marcon, Alessandro
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Public health ,Environmental Engineering ,Epidemiology ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Pollution ,Asthma ,Air quality ,Chronic bronchitis ,Rhinitis ,Chronic bronchiti ,Environmental Chemistry ,Waste Management and Disposal - Abstract
Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n=965), asthma (n=328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n=469), and controls (n=2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean±SD exposures were 28.7±6.0μg/m3 (PM10), 20.1±5.6μg/m3 (PM2.5), 27.2±9.7μg/m3 (NO2), and 70.8±4.2μg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10μg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10μg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.
- Published
- 2023
30. New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA)
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Susanna Esposito, Francesco Blasi, Nigel Curtis, Sheldon Kaplan, Tiziana Lazzarotto, Marianna Meschiari, Cristina Mussini, Maddalena Peghin, Carlos Rodrigo, Antonio Vena, Nicola Principi, and Matteo Bassetti
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Microbiology (medical) ,Staphylococcus aureus ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,MRSA ,MSSA ,Biochemistry ,Microbiology ,antibiotics ,anti-infective therapy ,Infectious Diseases ,antimicrobial resistance ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use.
- Published
- 2023
31. European cancer mortality predictions for the year 2023 with focus on lung cancer
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M. Malvezzi, C. Santucci, P. Boffetta, G. Collatuzzo, F. Levi, C. La Vecchia, and E. Negri
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Settore MED/17 - Malattie Infettive ,Settore MED/06 - Oncologia Medica ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Settore MED/42 - Igiene Generale e Applicata ,COVID-19 ,Hematology ,Settore MED/01 - Statistica Medica ,Europe ,prediction model ,lung cancer ,Oncology ,mortality rates ,cancer - Published
- 2023
32. Bone Disease in Long-Term Lung Transplant Survivors
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Giorgia Grassi, Elisa Cairoli, Lucrezia Maria Silvana Gentile, Iacopo Chiodini, Marta Zampogna, Alberto Ghielmetti, Letizia Corinna Morlacchi, Valeria Rossetti, Lorenzo Rosso, Ilaria Righi, Mario Nosotti, Maura Arosio, Francesco Blasi, and Cristina Eller Vainicher
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cystic fibrosis ,trabecular bone score ,Space and Planetary Science ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Settore MED/21 - Chirurgia Toracica ,lung transplantation ,Paleontology ,vertebral fractures ,General Biochemistry, Genetics and Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Settore MED/13 - Endocrinologia - Abstract
Background: During the first two years after lung transplantation (LTx), the incidence of fragility fractures (FX) is estimated to be 15–50% and it is lower in patients with cystic fibrosis (CF) as compared with other end-stage lung diseases (nCF). The aim of our study is to compare the skeletal outcomes, after the first 2 years post-LTx, in long-term survivors with CF and nCF. Materials and Methods: We evaluated the FX rate, the changes in bone mineral density (BMD) and trabecular bone score (TBS) in 68 patients (38 CF and 30 nCF) who underwent LTx in our center and with a follow-up after LTx longer than 5 years (7.3 ± 2.0 years). Results: After the second year post-LTx: (i) the FX rate was lower than during the first two years post-LTx (4.4 vs. 20.6%, p = 0.004), with no difference between CF and nCF patients (5.3 vs. 3.3%, p = 0.589); (ii) BMD at lumbar spine, femoral neck and total hip remained stable (−1.6 ± 1.0 vs. −1.4 ± 1.1, p = 0.431, −1.8 ± 0.9 vs. −1.9 ± 0.9, p = 0.683, −1.5 ± 0.9 vs. −1.4 ± 0.9, p = 0.678, respectively) as well as TBS (1.200 ± 0.124 vs. 1.199 ± 0.205, p = 0.166). Conclusions: After the second year post-LTx, the skeletal complications become less frequent and have similar incidence in patients with CF and nCF.
- Published
- 2023
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33. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults
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Ganesh Raghu, Martine Remy-Jardin, Luca Richeldi, Carey C. Thomson, Yoshikazu Inoue, Takeshi Johkoh, Michael Kreuter, David A. Lynch, Toby M. Maher, Fernando J. Martinez, Maria Molina-Molina, Jeffrey L. Myers, Andrew G. Nicholson, Christopher J. Ryerson, Mary E. Strek, Lauren K. Troy, Marlies Wijsenbeek, Manoj J. Mammen, Tanzib Hossain, Brittany D. Bissell, Derrick D. Herman, Stephanie M. Hon, Fayez Kheir, Yet H. Khor, Madalina Macrea, Katerina M. Antoniou, Demosthenes Bouros, Ivette Buendia-Roldan, Fabian Caro, Bruno Crestani, Lawrence Ho, Julie Morisset, Amy L. Olson, Anna Podolanczuk, Venerino Poletti, Moisés Selman, Thomas Ewing, Stephen Jones, Shandra L. Knight, Marya Ghazipura, Kevin C. Wilson, and Pulmonary Medicine
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progressive pulmonary fibrosis ,Pulmonary and Respiratory Medicine ,histopathology ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,respiratory system ,idiopathic pulmonary fibrosis ,Critical Care and Intensive Care Medicine ,radiology ,respiratory tract diseases - Abstract
Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana de Torax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results: 1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.
- Published
- 2022
34. Prescribing Patterns and Tolerability of Mycophenolate and Azathioprine in Patients with Nonidiopathic Pulmonary Fibrosis Fibrotic Interstitial Lung Disease
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Alyson W. Wong, Yet H. Khor, Kathryn Donohoe, Alessia Comes, Veronica Marcoux, Jolene H. Fisher, Kerri A. Johannson, Deborah Assayag, Julie Morisset, Shane Shapera, Nasreen Khalil, Charlene D. Fell, Helene Manganas, Gerard Cox, Teresa To, Andrea S. Gershon, Nathan Hambly, Andrew J. Halayko, Mohsen Sadatsafavi, Pearce G. Wilcox, Martin Kolb, Luca Richeldi, and Christopher J. Ryerson
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Pulmonary and Respiratory Medicine ,Azathioprine ,Humans ,onidiopathic Pulmonary Fibrosis Fibrotic Interstitial Lung Disease ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Lung Diseases, Interstitial ,Fibrosis ,Idiopathic Pulmonary Fibrosis ,Immunosuppressive Agents - Published
- 2022
35. Treatment options in obstructive sleep apnea
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Francesco Gambino, Marta Maria Zammuto, Alessandro Virzì, Giosafat Conti, Maria Rosaria Bonsignore, Gambino, Francesco, Zammuto, Marta Maria, Virzì, Alessandro, Conti, Giosafat, and Bonsignore, Maria Rosaria
- Subjects
Physiological phenotype ,Sleep Apnea, Obstructive ,Continuous Positive Airway Pressure ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Personalized medicine ,CPAP adherence ,Non-PAP treatment ,Treatment Outcome ,Clinical phenotype ,Weight Loss ,Emergency Medicine ,Internal Medicine ,Humans ,Female ,Life Style ,Mandibular Advancement - Abstract
Treatment of OSA with CPAP is currently the recommended treatment and has the greatest evidence of efficacy on AHI, symptoms and comorbidities. Symptomatic patients with moderate-severe OSA generally have good adherence to CPAP therapy, while those with mild OSA, female, young and generally paucisymptomatic, have lower CPAP adherence, especially in the medium and long term. The recent identification of different clinical and pathophysiological phenotypes of OSA has paved the way for alternative treatments to CPAP, leading to an increasingly personalized therapy. Weight loss and lifestyle modifications are highly recommended in all obese or overweight patients. Mandibular advancement devices (MAD), positional therapy (PT) and hypoglossal nerve stimulation (HSN) are recent and personalized alternative therapies on which there is promising and encouraging data but with still little strong scientific evidence. The purpose of this review is to compare the efficacy, adherence and costs of various therapeutic options for OSA patients in the light of recent evidence and to provide useful guidance for specialists.
- Published
- 2022
36. Early outcomes of 'low-risk' patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience
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Orlandi, R., Rinaldo, R.F., Mazzucco, A., Baccelli, A., Mondoni, M., Marchetti, F., Zagaria, M., Cefalo, J., Leporati, A., Montoli, M., Ghilardi, G., Baisi, A., and Centanni, S.
- Subjects
Settore MED/18 - Chirurgia Generale ,VO2peak ,postoperative outcomes ,cardiopulmonary complications ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Settore MED/21 - Chirurgia Toracica ,cardiopulmonary exercise testing (CPET) ,peak oxygen uptake ,thoracic surgery ,Surgery - Abstract
ObjectiveCardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing.MethodsRetrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period.ResultsA total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery.ConclusionsPostoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.
- Published
- 2023
37. Predittori clinici, radiologici e biologici di decorso clinico in pazienti con fibrosi polmonare idiopatica
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Cocconcelli, Elisabetta
- Subjects
Settore MED/10 - Malattie dell'Apparato Respiratorio - Published
- 2023
38. Comments on PD-1 Inhibitor for Disseminated Mycobacterium avium Infection in a Person Living With HIV
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Andrea Lombardi, Andrea Gramegna, Paola Gruarin, Renata Grifantini, Andrea Gori, Francesco Blasi, and Alessandra Bandera
- Subjects
Infectious Diseases ,Oncology ,Settore MED/17 - Malattie Infettive ,Settore MED/10 - Malattie dell'Apparato Respiratorio - Published
- 2023
39. Lung Transplantation From Controlled and Uncontrolled Donation After Circulatory Death (DCD) Donors With Long Ischemic Times Managed by Simple Normothermic Ventilation and Ex-Vivo Lung Perfusion Assessment
- Author
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Palleschi, A., Zanella, A., Citerio, G., Musso, V., Rosso, L., Tosi, D., Fumagalli, J., Bonitta, G., Benazzi, E., Lopez, G., Rossetti, V., Morlacchi, L.C., Uslenghi, C., Cardillo, M., Blasi, F., Grasselli, G., Valenza, F., Nosotti, M., Palleschi, A, Zanella, A, Citerio, G, Musso, V, Rosso, L, Tosi, D, Fumagalli, J, Bonitta, G, Benazzi, E, Lopez, G, Rossetti, V, Morlacchi, L, Uslenghi, C, Cardillo, M, Blasi, F, Grasselli, G, Valenza, F, and Nosotti, M
- Subjects
donation after circulatory death donors ,Transplantation ,chronic lung allograft dysfunction ,ischemia time ,lung preservation ,lung transplantation ,primary graft dysfunction ,donation after circulatory death donor ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Settore MED/21 - Chirurgia Toracica ,Settore MED/41 - Anestesiologia - Abstract
Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved in-vivo through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day, p = 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.
- Published
- 2023
40. Exploring the Role of Immune System and Inflammatory Cytokines in SARS-CoV-2 Induced Lung Disease: A Narrative Review
- Author
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Claudio Tirelli, Mara De Amici, Cristina Albrici, Sabrina Mira, Giulia Nalesso, Beatrice Re, Angelo Guido Corsico, Michele Mondoni, and Stefano Centanni
- Subjects
General Immunology and Microbiology ,SARS-CoV-2 ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,COVID-19 ,cytokine storm ,immune system ,immunotherapy ,vaccine ,ARDS ,innate immune system ,adaptive immune system ,General Biochemistry, Genetics and Molecular Biology ,General Agricultural and Biological Sciences - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of coronavirus disease 19 (COVID-19). COVID-19 can manifest with a heterogenous spectrum of disease severity, from mild upper airways infection to severe interstitial pneumonia and devastating acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection may induce an over activation of the immune system and the release of high concentrations of pro-inflammatory cytokines, leading to a “cytokine storm”, a recognized pathogenetic mechanism in the genesis of SARS-CoV-2-induced lung disease. This overproduction of inflammatory cytokines has been recognized as a poor prognostic factor, since it can lead to disease progression, organ failure, ARDS and death. Moreover, the immune system shows dysregulated activity, particularly through activated macrophages and T-helper cells and in the co-occurrent exhaustion of lymphocytes. We carried out a non-systematic literature review aimed at providing an overview of the current knowledge on the pathologic mechanisms played by the immune system and the inflammation in the genesis of SARS-CoV-2-induced lung disease. An overview on potential treatments for this harmful condition and for contrasting the “cytokine storm” has also been presented. Finally, a look at the experimented experimental vaccines against SARS-CoV-2 has been included.
- Published
- 2023
41. Treatable traits in interstitial lung diseases: a call to action
- Author
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Francesco Amati, Paolo Spagnolo, Justin M Oldham, Christopher J Ryerson, Anna Stainer, Andrea Gramegna, Marco Mantero, Donato Lacedonia, Nicola Sverzellati, Luca Richeldi, Francesco Blasi, and Stefano Aliberti
- Subjects
Pulmonary and Respiratory Medicine ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,interstitial lung diseases - Published
- 2023
42. SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
- Author
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Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, and Marco Cipolli
- Subjects
cystic fibrosis ,COVID-19 ,SARS-CoV-2 ,vaccine ,Multidisciplinary ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. Instead, current clinical evidence seems to be heading in the opposite direction. To clarify whether host factors expressed by the Cystic Fibrosis epithelia may influence coronavirus disease 2019 progression, here we describe the expression of SARS-CoV-2 receptors in primary airway epithelial cells. We show that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral entry and replication in Cystic Fibrosis cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin 6 in healthy donor-derived primary airway epithelial cells, but a very weak response in primary Cystic Fibrosis cells. Collectively, these data support that Cystic Fibrosis condition may be at least partially protecting from SARS-CoV-2 infection.
- Published
- 2023
43. Idiopathic pulmonary fibrosis is associated with common genetic variants and limited rare variants
- Author
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Anna L. Peljto, Rachel Z. Blumhagen, Avram D. Walts, Jonathan Cardwell, Julia Powers, Tamera J. Corte, Joanne L. Dickinson, Ian Glaspole, Yuben P. Moodley, Martina Koziar Vasakova, Elisabeth Bendstrup, Jesper R. Davidsen, Raphael Borie, Bruno Crestani, Philippe Dieude, Francesco Bonella, Ulrich Costabel, Gunnar Gudmundsson, Seamas C. Donnelly, Jim Egan, Michael T. Henry, Michael P. Keane, Marcus P. Kennedy, Cormac McCarthy, Aoife N. McElroy, Joshua A. Olaniyi, Katherine M. A. O’Reilly, Luca Richeldi, Paolo M. Leone, Venerino Poletti, Francesco Puppo, Sara Tomassetti, Valentina Luzzi, Nurdan Kokturk, Nesrin Mogulkoc, Christine A. Fiddler, Nikhil Hirani, R. Gisli Jenkins, Toby M. Maher, Philip L. Molyneaux, Helen Parfrey, Rebecca Braybrooke, Timothy S. Blackwell, Peter D. Jackson, Steven D. Nathan, Mary K. Porteous, Kevin K. Brown, Jason D. Christie, Harold R. Collard, Oliver Eickelberg, Elena E. Foster, Kevin F. Gibson, Marilyn Glassberg, Daniel J. Kass, Jonathan A. Kropski, David Lederer, Angela L. Linderholm, Jim Loyd, Susan K. Mathai, Sydney B. Montesi, Imre Noth, Justin M. Oldham, Amy J. Palmisciano, Cristina A. Reichner, Mauricio Rojas, Jesse Roman, Neil Schluger, Barry S. Shea, Jeffrey J. Swigris, Paul J. Wolters, Yingze Zhang, Cecilia M. A. Prele, Juan I. Enghelmayer, Maria Otaola, Christopher J. Ryerson, Mauricio Salinas, Martina Sterclova, Tewodros H. Gebremariam, Marjukka Myllärniemi, Roberto G. Carbone, Haruhiko Furusawa, Masaki Hirose, Yoshikazu Inoue, Yasunari Miyazaki, Ken Ohta, Shin Ohta, Tsukasa Okamoto, Dong Soon Kim, Annie Pardo, Moises Selman, Alvaro U. Aranda, Moo Suk Park, Jong Sun Park, Jin Woo Song, Maria Molina-Molina, Lurdes Planas-Cerezales, Gunilla Westergren-Thorsson, Albert V. Smith, Ani W. Manichaikul, John S. Kim, Stephen S. Rich, Elizabeth C. Oelsner, R. Graham Barr, Jerome I. Rotter, Josee Dupuis, George O’Connor, Ramachandran S. Vasan, Michael H. Cho, Edwin K. Silverman, Marvin I. Schwarz, Mark P. Steele, Joyce S. Lee, Ivana V. Yang, Tasha E. Fingerlin, and David A. Schwartz
- Subjects
Pulmonary and Respiratory Medicine ,Whole Genome Sequencing ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Critical Care and Intensive Care Medicine ,Interstitial Lung Disease ,TOPMed ,Telomerase ,Genetic Association Studies - Abstract
Rationale: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
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- 2023
44. The Future of Clinical Trials in Idiopathic Pulmonary Fibrosis
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Anna J. Podolanczuk, Luca Richeldi, and Fernando J. Martinez
- Subjects
General Medicine ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Idiopathic Pulmonary Fibrosis - Published
- 2023
45. Predictors of Stability/Improvement of Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis After One Year of Treatment With Nintedanib
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Michele Mondoni, Francesco Varone, Fausta Alfano, Giuseppe Muscato, Caterina Conti, Laura Saderi, Bruno Iovene, Fabiano Di Marco, Carlo Vancheri, Luca Richeldi, Stefano Centanni, and Giovanni Sotgiu
- Subjects
Pulmonary and Respiratory Medicine ,idiopathic Pulmonary Fibrosis ,Settore MED/10 - Malattie dell'Apparato Respiratorio - Published
- 2023
46. Monitoring small airway dysfunction in connective tissue disease-related interstitial lung disease: a retrospective and prospective study
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Linrui Xu, Giacomo Sgalla, Faping Wang, Min Zhu, Liangyuan Li, Ping Li, Qibing Xie, Xiaoyan Lv, Jianqun Yu, Gang Wang, Huajing Wan, Luca Richeldi, and Fengming Luo
- Subjects
Pulmonary and Respiratory Medicine ,Pulmonary function ,Small airway dysfunction ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Treatment response ,Connective tissue disease associated interstitial lung disease - Abstract
Background Small airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored. Methods We conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment. Results CTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters. Conclusion In our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.
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- 2023
47. Reply to: Cottin et al., Johannson et al., Scholand and Wells, and Crowley et al
- Author
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Ganesh Raghu, Luca Richeldi, Carey C Thomson, Martine Remy-Jardin, and Kevin C Wilson
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Pulmonary and Respiratory Medicine ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,progressive pulmonary fibrosis (PPF) ,Critical Care and Intensive Care Medicine - Published
- 2023
48. Observational, Multicenter Study on the Efficacy, Tolerability, and Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis Older than 80 Years
- Author
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Michele Mondoni, Fausta Alfano, Francesco Varone, Giuseppe Muscato, Caterina Conti, Laura Saderi, Amerigo Chiesa, Fabiano Di Marco, Carlo Vancheri, Luca Richeldi, Stefano Centanni, and Giovanni Sotgiu
- Subjects
Pulmonary and Respiratory Medicine ,Elderly ,Nintedanib ,Settore MED/10 - Malattie dell'Apparato Respiratorio ,Antifibrotic therapy ,Exacerbation ,Idiopathic pulmonary fibrosis ,Safety - Abstract
Background: Idiopathic pulmonary fibrosis (IPF) primarily affects old patients. Old age is a predictor of mortality. Nintedanib, the only antifibrotic drug approved in Italy for patients aged >80 years, can slow the progression of IPF by reducing the rate of decline in forced vital capacity (FVC) and the risk of exacerbations. Objectives: The primary aim of the study was to compare the decline of FVC after 12 months of nintedanib in patients aged >80 years versus younger patients. Differences related to other functional data, safety, tolerability, hospitalizations, exacerbations, and mortality were evaluated. Methods: An observational, retrospective, multicenter study was carried out in Italy. Results: 159 (122 [76.7%] males) patients were recruited: 106 (66.7%) aged ≤80 years and 53 (33.3%) aged >80 years. FVC decline after 12 months of therapy was not significantly different (−45 mL [−170; 75] vs. −20 mL [−138; 110] mL; p: 0.51). No differences were found for other functional data. Diarrhea was the most frequent adverse event (AE). Rate and type of any AEs, permanent/temporary dose reduction, or drug discontinuation were not significantly different between patients aged ≤80 vs. >80 years. Furthermore, acute exacerbations, hospitalization, and mortality were not significantly different. Conclusions: Nintedanib is effective and safe in patients with IPF aged >80 years, and no significant differences were found when clinical outcomes were compared with those of younger patients. Thus, older age should not be a barrier for the early prescription of antifibrotic treatment in IPF patients.
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- 2023
49. Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials
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Maher, Toby M, Ford, Paul, Brown, Kevin K, Costabel, Ulrich, Cottin, Vincent, Danoff, Sonye K, Groenveld, Irene, Helmer, Eric, Jenkins, R Gisli, Milner, Julie, Molenberghs, Geert, Penninckx, Bjorn, Randall, Matthew J, Van Den Blink, Bernt, Fieuw, Ann, Vandenrijn, Charlotte, Rocak, Sanda, Seghers, Ineke, Shao, Lixin, Taneja, Amit, Jentsch, Garrit, Watkins, Timothy R, Wuyts, Wim A, Kreuter, Michael, Verbruggen, Nadia, Prasad, Niyati, Wijsenbeek, Marlies, S, and Richeldi, Luca
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Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,Idiopathic Pulmonary Fibrosis - Published
- 2023
50. Plain language summary
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Richeldi, Luca, Azuma, Arata, Cottin, Vincent, Hesslinger, Christian, Stowasser, Susanne, Valenzuela, Claudia, Wijsenbeek, Marlies S., Zoz, Donald F., Voss, Florian, Maher, Toby M., and Pulmonary Medicine
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treatment ,SDG 3 - Good Health and Well-being ,Health Policy ,Idiopathic pulmonary fibrosis ,clinical trial ,phosphodiesterase 4B inhibitor ,Settore MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,lay summary ,plain language summary - Abstract
What is this summary about? This plain language summary describes the main findings from a trial in people with idiopathic pulmonary fibrosis (also called IPF) that was recently published in the New England Journal of Medicine . IPF is a rare disease, where the lungs become more and more scarred, with breathing and oxygen uptake becoming increasingly difficult. This trial looked at the medication BI 1015550 as a potential treatment for IPF. It compared BI 1015550 to placebo (a dummy drug that does not contain any active ingredients) to investigate the effectiveness of the drug in treating people with IPF. The study also looked at the additional medical issues (referred to as adverse events) reported during the study. Some participants took approved treatments to reduce scarring (nintedanib or pirfenidone), and some did not. What were the results? Overall, 147 people with IPF from 22 countries took part in the trial. The results showed that BI 1015550 prevented lung function from decreasing in people with IPF. There was no difference in the percentage of patients with medical issues rated as severe by the study physician with BI 1015550 or placebo. However, more people treated with BI 1015550 had diarrhoea. Among those treated with BI 1015550, 13 participants stopped their treatment due to medical issues, whereas treatment was not stopped due to medical issues for any participants treated with placebo. What do the results mean? These results provide evidence that BI 1015550 prevents lung function from worsening in people with IPF. Further clinical studies will be conducted in the future to test BI 1015550 in a larger group of people with IPF and other forms of lung scarring that get worse over time, and for a longer time period.
- Published
- 2023
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