European Respiratory Journal最新文献

{"title":"Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA.","authors":"Elizabeth A Cromwell, Josh S Ostrenga, Don B Sanders, Wayne Morgan, Carlo Castellani, Rhonda Szczesniak, Pierre-Regis Burgel","doi":"10.1183/13993003.01146-2024","DOIUrl":"10.1183/13993003.01146-2024","url":null,"abstract":"<p><strong>Background: </strong>Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on <i>in vitro</i> data in the USA for those carrying at least one of 177 rare <i>CFTR</i> (cystic fibrosis transmembrane conductance regulator) variants.</p><p><strong>Methods: </strong>PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV₁) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.</p><p><strong>Results: </strong>A total of 1791 individuals aged ≥6 years with rare <i>CFTR</i> variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV₁ % pred by +3.39 (95% CI 2.14-4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38-0.79). These effects were greater in individuals naïve of previous CFTR modulators.</p><p><strong>Conclusions: </strong>Extension of the ETI label to rare <i>CFTR</i> variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125254","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":"Until it's done for everyone: the role of CFTR modulator label expansion.","authors":"Clemente J Britto, Jennifer L Taylor-Cousar","doi":"10.1183/13993003.01898-2024","DOIUrl":"10.1183/13993003.01898-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617685","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":"RUNX2 is stabilised by TAZ and drives pulmonary artery calcification and lung vascular remodelling in pulmonary hypertension due to left heart disease.","authors":"Shao-Fei Liu, Mariya M Kucherenko, Pengchao Sang, Qiuhua Li, Juquan Yao, Netra Nambiar Veetil, Tara Gransar, Ioana Alesutan, Jakob Voelkl, Gabriela Salinas, Jana Grune, Szandor Simmons, Christoph Knosalla, Wolfgang M Kuebler","doi":"10.1183/13993003.00844-2023","DOIUrl":"10.1183/13993003.00844-2023","url":null,"abstract":"<p><strong>Background: </strong>Calcification is common in chronic vascular disease, yet its role in pulmonary hypertension due to left heart disease is unknown. Here, we probed for the role of runt-related transcription factor-2 (RUNX2), a master transcription factor in osteogenesis, and its regulation by the HIPPO pathway transcriptional coactivator with PDZ-binding motif (TAZ) in the osteogenic reprogramming of pulmonary artery smooth muscle cells and vascular calcification in patients with pulmonary hypertension due to left heart disease. We similarly examined its role using an established rat model of pulmonary hypertension due to left heart disease induced by supracoronary aortic banding.</p><p><strong>Methods: </strong>Pulmonary artery samples were collected from patients and rats with pulmonary hypertension due to left heart disease. Genome-wide RNA sequencing was performed, and pulmonary artery calcification assessed. Osteogenic signalling <i>via</i> TAZ and RUNX2 was delineated by protein biochemistry. <i>In vivo</i>, the therapeutic potential of RUNX2 or TAZ inhibition by CADD522 or verteporfin was tested in the rat model.</p><p><strong>Results: </strong>Gene ontology term analysis identified significant enrichment in ossification and osteoblast differentiation genes, including <i>RUNX2</i>, in pulmonary arteries of patients and lungs of rats with pulmonary hypertension due to left heart disease. Pulmonary artery calcification was evident in both patients and rats. Both TAZ and RUNX2 were upregulated and activated in pulmonary artery smooth muscle cells of patients and rats. Co-immunoprecipitation revealed a direct interaction of RUNX2 with TAZ in pulmonary artery smooth muscle cells. TAZ inhibition or knockdown decreased RUNX2 abundance due to accelerated RUNX2 protein degradation rather than reduced <i>de novo</i> synthesis. Inhibition of either TAZ or RUNX2 attenuated pulmonary artery calcification, distal lung vascular remodelling and pulmonary hypertension development in the rat model.</p><p><strong>Conclusion: </strong>Pulmonary hypertension due to left heart disease is associated with pulmonary artery calcification that is driven by TAZ-dependent stabilisation of RUNX2, causing osteogenic reprogramming of pulmonary artery smooth muscle cells. The TAZ-RUNX2 axis may present a therapeutic target in pulmonary hypertension due to left heart disease.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617677","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":"Determination of loss of chromosome Y in peripheral blood cells in males with idiopathic pulmonary fibrosis.","authors":"Magali Espinosa, Iliana Herrera, Ivette Buendía-Roldán, Jorge Meléndez-Zajgla, Annie Pardo, Moisés Selman","doi":"10.1183/13993003.01303-2024","DOIUrl":"10.1183/13993003.01303-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371412","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":"European Respiratory Society guidelines for the diagnosis and management of pulmonary alveolar proteinosis.","authors":"Cormac McCarthy, Francesco Bonella, Marissa O'Callaghan, Clairelyne Dupin, Tiago Alfaro, Markus Fally, Raphael Borie, Ilaria Campo, Vincent Cottin, Aurelie Fabre, Matthias Griese, Alice Hadchouel, Stephane Jouneau, Maria Kokosi, Effrosyni Manali, Helmut Prosch, Bruce C Trapnell, Marcel Veltkamp, Tisha Wang, Ingrid Toews, Alexander G Mathioudakis, Elisabeth Bendstrup","doi":"10.1183/13993003.00725-2024","DOIUrl":"10.1183/13993003.00725-2024","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP.</p><p><strong>Methods: </strong>A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations.</p><p><strong>Results: </strong>The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy.</p><p><strong>Conclusions: </strong>The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987795","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":"Going astray with a smoking <i>Traviata</i>?","authors":"Joan B Soriano, Michael Studnicka","doi":"10.1183/13993003.01887-2024","DOIUrl":"10.1183/13993003.01887-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617666","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":"Inhaled soluble guanylate cyclase stimulator for the treatment of pulmonary arterial hypertension: struggling to breathe easy.","authors":"Colm McCabe, S John Wort","doi":"10.1183/13993003.01658-2024","DOIUrl":"10.1183/13993003.01658-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617673","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":"ERJ advances: epigenetic ageing and leveraging DNA methylation in chronic respiratory diseases.","authors":"Ana I Hernandez Cordero, Janice M Leung","doi":"10.1183/13993003.01257-2024","DOIUrl":"10.1183/13993003.01257-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371413","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":"Perspective on WHO implementation guidance on TB infection prevention and control.","authors":"Onno W Akkerman, G B Migliori, Dennis Falzon, Alberto L Garcia-Basteiro, Avinash Kanchar, Olha Konstantynovska, Fusun Oner Eyuboglu, Raquel Duarte","doi":"10.1183/13993003.00109-2024","DOIUrl":"https://doi.org/10.1183/13993003.00109-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617664","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":"TAZ and RUNX2 awareness in pulmonary hypertension due to left heart disease.","authors":"Vinicio A de Jesus Perez, Yen-Chun Lai","doi":"10.1183/13993003.00905-2024","DOIUrl":"10.1183/13993003.00905-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142617681","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}