European Respiratory Journal最新文献

{"title":"Pirfenidone in post-COVID19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomized clinical trial.","authors":"Guadalupe Bermudo, Belén Del Rio, Vanesa Vicens-Zygmunt, Jaume Bordas-Martinez, Marta Hernández, Claudia Valenzuela, Rosalía Laporta, Juan Rigual Bobillo, Karina Portillo, Paloma Millán-Billi, Eva Balcells, Diana Badenes-Bonet, Santi Bolivar, José-Antonio Rodríguez-Portal, Cecilia López Ramirez, Laura Tomás, Koral Fernández de Roitegi, Jacobo Sellarés, Diego Castillo, Jessica González, Silvia Barril, Yasmina Gutiérrez-Rodríguez, Paloma Caballero, Javier Alarcon, Judith Peñafiel, Jose Sanz-Santos, Rosana Blavia, Cristina Caupena, Pilar Segovia, Salud Santos-Pérez, Anna Ferrer, Maria B Badia, Pilar Hereu, Mireya Fuentes, Ana Montes-Worboys, Tomás Franquet, Patricio Luburich, María Molina-Molina","doi":"10.1183/13993003.02249-2024","DOIUrl":"https://doi.org/10.1183/13993003.02249-2024","url":null,"abstract":"<p><strong>Background: </strong>Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia was evaluated.</p><p><strong>Methods: </strong>Phase 2, double-blind, placebo-controlled, Spanish multicenter clinical trial randomized to receive pirfenidone or placebo (2:1) for 24-weeks. The primary endpoint was the proportion of patients that improved, considered when percent change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score chest high-resolution computed tomography (HRCT). Secondary endpoints included health-related quality of life (HRQoL), exercise capacity, and drug safety profile.</p><p><strong>Results: </strong>From 119 eligible patients, 113 were randomized and 103 were analyzed (pirfenidone n=69, placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and body-mass index was 29 kg·m^-2. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% <i>versus</i> 82.3%, respectively). The mean predicted FVC (%) increased 12.74 (20.6) with pirfenidone and 4.35 (22.3) with placebo (p=0.071), and the HRCT (%) fibrotic score reduced 5.44 (3.69) with pirfenidone and 2.57 (2.59) with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in pirfenidone and 39.4% in placebo group, respectively). Exercise capacity, adverse events and hospitalizations were similar between groups. No deaths were reported.</p><p><strong>Conclusions: </strong>The overall improvement in lung function and the HRCT fibrotic score after 6 months with pirfenidone was not significantly different than placebo.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in detecting small airway disease with medical imaging.","authors":"Kalysta Makimoto, Gaurav Veer Singh, Miranda Kirby","doi":"10.1183/13993003.00212-2025","DOIUrl":"https://doi.org/10.1183/13993003.00212-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD: FRONTIER-4.","authors":"Dave Singh, Patricia Guller, Fred Reid, Sarah Doffman, Ulla Seppälä, Ioannis Psallidas, Rachel Moate, Rebecca Smith, Joanna Kiraga, Eulalia Jimenez, Dennis Brooks, Aoife Kelly, Lars H Nordenmark, Muhammad Waqas Sadiq, Luis Mateos Caballero, Chris Kell, Maria G Belvisi, Hitesh Pandya","doi":"10.1183/13993003.02231-2024","DOIUrl":"https://doi.org/10.1183/13993003.02231-2024","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-33 may have a role in COPD pathobiology. FRONTIER-4 (NCT04631016) investigated tozorakimab (an anti-IL-33 monoclonal antibody) in moderate-to-severe COPD patients with chronic bronchitis receiving dual or triple inhaled therapy.</p><p><strong>Methods: </strong>FRONTIER-4 was a phase 2a, randomized, double-blind, placebo-controlled study. Patients received tozorakimab 600 mg or placebo subcutaneously every 4 weeks for 24 weeks. The primary endpoint was change in pre-bronchodilator (BD) FEV₁ from baseline to week 12. Secondary outcomes included post-BD FEV₁, time-to-first COPDCompEx event and safety.</p><p><strong>Results: </strong>The intent-to-treat population included 135 patients (tozorakimab, n=67; placebo, n=68). At week 12 in the intent-to-treat population, tozorakimab showed a greater increase from baseline in pre-BD FEV₁ (least-squares mean [LSM]: 24 mL [80% confidence interval (CI): -15,63]; p=0.216) that was not statistically significant, and in post-BD FEV₁ (LSM: 67 mL [80% CI: 17,116]; p=0.044), when compared with placebo. Tozorakimab showed improvements <i>versus</i> placebo (LSM [80% CI]) in change from baseline in pre-BD FEV₁ (69 mL [9,130]; p=0.072) and post-BD FEV₁ (124 mL [47,201]; p=0.020) at week 12 in a pre-specified subgroup of patients with ≥2 prior exacerbations. Tozorakimab did not significantly reduce the risk of COPDCompEx events (HR: 0.79 [80% CI: 0.57,1.11]; p=0.186) in the intent-to-treat population, although there were greater effects in patients with ≥2 prior exacerbations (hazard ratio: 0.61 [80% CI: 0.37,1.00]). Results were similar in former and current smokers. Tozorakimab was well tolerated.</p><p><strong>Conclusion: </strong>Although the primary endpoint was not met in the intent-to-treat population, tozorakimab showed positive efficacy signals <i>versus</i> placebo in a subgroup of patients with COPD with a high risk of exacerbations.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP/TAZ are Crucial Regulator of Macrophage-mediated Pulmonary Inflammation and Fibrosis after Bleomycin-induced Injury.","authors":"Masum M Mia, Siti Aishah Binte Abdul Ghani, Dasan Mary Cibi, Hanumakumar Bogireddi, Uthayanan Nilanthi, Ashwatthaman Selvan, Wai Shiu Fred Wong, Manvendra K Singh","doi":"10.1183/13993003.01544-2023","DOIUrl":"10.1183/13993003.01544-2023","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is the most prevalent and severe form of end-stage interstitial lung disease. Macrophages are crucial players in inflammation-induced PF, but the mechanisms driving macrophage polarization and their specific roles in PF pathogenesis remain poorly understood. Here, we demonstrate that both YAP and TAZ are activated in lung macrophages from patients with PF as well as in mice with bleomycin-induced PF. Myeloid-specific <i>Yap/Taz</i> deletion resulted in reduced recruitment of monocyte-derived alveolar macrophages (Mo-AMs), impaired inflammatory responses, decreased PF, and enhanced alveolar epithelial cell regeneration following bleomycin treatment. Conversely, the expression of a constitutively active YAP mutant (YAP^5SA) exacerbated bleomycin-induced PF by increasing Mo-AM recruitment, elevating expression of proinflammatory and profibrotic markers, and impairing alveolar epithelial cell regeneration. We demonstrate that YAP/TAZ-CCL2 signaling plays a crucial role in bleomycin-induced PF, as blocking CCL2 with a neutralizing antibody effectively abrogated the YAP^5SA-induced recruitment of Mo-AMs, inflammatory and fibrotic responses. Additionally, we reveal that the YAP/TAZ-MBD2-TGFβ1-pSMAD2 signaling axis is crucial not only for profibrotic macrophage polarization but also for their crosstalk with lung fibroblasts, driving the fibroblast-to-myofibroblast transition. Collectively, these findings suggest that targeting aberrant YAP/TAZ activity to modulate inflammatory and fibrotic response could be a promising strategy for the prevention and treatment of PF.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaping and lung health: less known unknowns.","authors":"Joan B Soriano, Josep Morera, Julio Ancochea","doi":"10.1183/13993003.02482-2024","DOIUrl":"https://doi.org/10.1183/13993003.02482-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 3","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-centred composite scores as tools for assessment of response to biological therapy for paediatric and adult severe asthma.","authors":"Ekaterina Khaleva, Chris Brightling, Thomas Eiwegger, Alan Altraja, Philippe Bégin, Katharina Blumchen, Apostolos Bossios, Arnaud Bourdin, Anneke Ten Brinke, Guy Brusselle, Roxana Silvia Bumbacea, Andrew Bush, Thomas B Casale, Graham W Clarke, Rekha Chaudhuri, Kian Fan Chung, Courtney Coleman, Jonathan Corren, Sven-Erik Dahlén, Antoine Deschildre, Ratko Djukanovic, Katrien Eger, Andrew Exley, Louise Fleming, Stephen J Fowler, Erol A Gaillard, Monika Gappa, Atul Gupta, Hans Michael Haitchi, Simone Hashimoto, Liam G Heaney, Gunilla Hedlin, Markaya Henderson, Wen Hua, David J Jackson, Bülent Karadag, Constance Helen Katelaris, Mariko S Koh, Matthias Volkmar Kopp, Gerard H Koppelman, Inger Kull, Ramesh J Kurukulaaratchy, Ji-Hyang Lee, Vera Mahler, Mika Mäkelä, Matthew Masoli, Alexander G Mathioudakis, Angel Mazon, Erik Melén, Katrin Milger, Alexander Moeller, Clare S Murray, Prasad Nagakumar, Parameswaran Nair, Jenny Negus, Antonio Nieto, Nikolaos G Papadopoulos, James Paton, Mariëlle W Pijnenburg, Katharine C Pike, Celeste Porsbjerg, Anna Rattu, Hitasha Rupani, Franca Rusconi, Niels W Rutjes, Sejal Saglani, Paul Seddon, Salman Siddiqui, Florian Singer, Tomoko Tajiri, Steve Turner, John W Upham, Susanne J H Vijverberg, Peter A B Wark, Michael E Wechsler, Valentyna Yasinska, Graham Roberts","doi":"10.1183/13993003.00691-2024","DOIUrl":"10.1183/13993003.00691-2024","url":null,"abstract":"<p><strong>Background: </strong>We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biological therapies for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life.</p><p><strong>Methods: </strong>International expert healthcare professionals and patients with severe asthma were invited to 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA, 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of healthcare professionals evaluated CONFiRM's external validity.</p><p><strong>Results: </strong>Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroid use were rated as the most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between healthcare professionals and patients, although patients assigned greater importance to quality of life. The CONFiRM score quantified response to a biologic from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (area under the curve ≥0.92) and a substantial (area under the curve ≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult, respectively; p<0.0001).</p><p><strong>Conclusions: </strong>We have developed novel patient-centred paediatric and adult CONFiRMs that include quality of life measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>ERJ</i> Podcast March 2025: Generalisability of pharmaceutical randomised controlled trial eligibility criteria for progressive pulmonary fibrosis.","authors":"","doi":"10.1183/13993003.E6503-2025","DOIUrl":"https://doi.org/10.1183/13993003.E6503-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 3","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Lung transcriptome of e-cigarette users reveals changes related to chronic lung disease.\" B. Kidane, S. Kahnamoui, S. Srinathan, R. Liu, L. Tan, M. Morris, A. Shawyer, A.J. Halayko and C.D. Pascoe. <i>Eur Respir J</i> 2024; 63: 2301623.","authors":"","doi":"10.1183/13993003.51623-2023","DOIUrl":"10.1183/13993003.51623-2023","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 3","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What can lockdowns tell us about the underlying causes of asthma exacerbations? A retrospective cohort study.","authors":"Arnaud Bourdin, Erika Nogué, Eric Matzner-Lober, Nicolas Malafaye, Isabelle Vachier, Sarah Skinner, Jerry Krishnan, Nicolas Molinari","doi":"10.1183/13993003.02264-2024","DOIUrl":"10.1183/13993003.02264-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposal for a rational and sustainable use of antimicrobial filters in pulmonary function testing.","authors":"Santiago C Arce, Javier C Brea Folco, Roque A Baldasaria","doi":"10.1183/13993003.02382-2024","DOIUrl":"10.1183/13993003.02382-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}