European Respiratory Journal最新文献

{"title":"Up-regulated matrix metalloproteinase activity in soil-transmitted helminth-tuberculosis co-infection is associated with increased lung pathology.","authors":"Maria-Cristina I Loader, Sory Vasquez Alves, Robert H Gilman, Jorge Coronel, Carmen Taquiri, Neusa Vasquez Alves, Fabiola Díaz-Soria, Salomón Durand, Sean T Kelleher, Teresa Jacob, William H Elson, Daniela E Kirwan, Jon S Friedland","doi":"10.1183/13993003.01445-2024","DOIUrl":"10.1183/13993003.01445-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064841","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":"List of <i>European Respiratory Journal</i> peer reviewers 2024.","authors":"","doi":"10.1183/13993003.16501-2025","DOIUrl":"https://doi.org/10.1183/13993003.16501-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064778","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":"Accelerated epigenetic aging worsens survival and mediates environmental stressors in fibrotic interstitial lung disease.","authors":"Gillian C Goobie, Daniel-Costin Marinescu, Ayodeji Adegunsoye, Jean Bourbeau, Christopher Carlsten, Rachel L Clifford, Dany Doiron, Qingling Duan, Kevin F Gibson, Amanda Grant-Orser, Ana I Hernandez Cordero, Kerri A Johannson, Daniel J Kass, Sharon E Kim, Janice M Leung, Xiaoyun Li, Wan Tan, Chen Xi Yang, S Mehdi Nouraie, Christopher J Ryerson, Tillie L Hackett, Yingze Zhang","doi":"10.1183/13993003.01618-2024","DOIUrl":"https://doi.org/10.1183/13993003.01618-2024","url":null,"abstract":"<p><strong>Background: </strong>The role of epigenetic aging in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter ≤2.5 μm (PM_2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic aging, and whether epigenetic age is associated with adverse clinical outcomes in patients with fILD.</p><p><strong>Methods: </strong>This multicentre, international, cohort study included patients with fILD from the University of Pittsburgh (UPitt, n=306) and University of British Columbia (UBC, n=170). Five-year PM_2.5 exposures were estimated using satellite-derived models. Neighbourhood disadvantage was calculated using U.S. and Canadian Census-based metrics. Epigenetic age difference (EAD=epigenetic age - chronological age) was calculated using GrimAge analysis of blood DNA methylation data. Linear models assessed associations of exposures with EAD. Cox models assessed associations of EAD with transplant-free survival. Causal mediation analysis evaluated EAD mediation of exposure-survival relationships.</p><p><strong>Results: </strong>Median epigenetic age was 11.7 years older than chronological age in patients with fILD. In combined cohort analysis, each interquartile range (IQR) PM_2.5 increase was associated with 2.88 years (95%CI 1.39-4.38, p<0.001) increased EAD. In UPitt, each IQR neighbourhood disadvantage increase was associated with 1.16 years (95%CI 0.22-2.09, p=0.02) increased EAD. Increased EAD was associated with worse transplant-free survival (HR=1.17 per 1-year increase EAD, 95%CI 1.10-1.24, p<0.001), with EAD mediating 40% of PM_2.5-survival relationship and 59% of neighbourhood disadvantage-survival relationships. Epigenetic age was also more strongly associated with transplant-free survival than chronological age.</p><p><strong>Conclusions: </strong>Epigenetic age acceleration is associated with worse survival and mediates adverse exposure impacts in fILD.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064844","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":"The acute effect of e-cigarette use on pulmonary function: a nonrandomised controlled trial.","authors":"Simanta Roy, Sreshtha Chowdhury, Tarana Ferdous, Rime Jebai, Wasim Maziak","doi":"10.1183/13993003.02140-2024","DOIUrl":"10.1183/13993003.02140-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881754","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":"The <i>European Respiratory Journal</i>: our drive to thrive in '25!","authors":"James D Chalmers, Neil J Bullen, Don D Sin","doi":"10.1183/13993003.00047-2025","DOIUrl":"https://doi.org/10.1183/13993003.00047-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064837","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":"Real-world health data potential for economic insights in COPD.","authors":"Pierrick Bedouch, Sébastien Chanoine","doi":"10.1183/13993003.02188-2024","DOIUrl":"https://doi.org/10.1183/13993003.02188-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064833","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":"Trajectories of responses to mepolizumab in severe asthma.","authors":"Santi Nolasco, Manali Mukherjee, Parameswaran Nair","doi":"10.1183/13993003.02023-2024","DOIUrl":"https://doi.org/10.1183/13993003.02023-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064839","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":"Efficacy and safety of the activin signalling inhibitor, sotatercept, in a pooled analysis of PULSAR and STELLAR studies.","authors":"Marius M Hoeper, Mardi Gomberg-Maitland, David B Badesch, J Simon R Gibbs, Ekkehard Grünig, Grzegorz Kopeć, Vallerie V McLaughlin, Gisela Meyer, Karen M Olsson, Ioana R Preston, Stephan Rosenkranz, Rogerio Souza, Aaron B Waxman, Loïc Perchenet, James Strait, Aiwen Xing, Solaiappan Manimaran, Xuelong Wang, Barry Miller, Alexandra G Cornell, Janethe de Oliveira Pena, H Ardeschir Ghofrani, Marc Humbert","doi":"10.1183/13993003.01424-2024","DOIUrl":"https://doi.org/10.1183/13993003.01424-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Sotatercept is a first-in-class activin signalling inhibitor that acts to restore the balance between the growth-promoting and growth-inhibiting signalling pathways.</p><p><strong>Methods: </strong>This post-hoc, exploratory, pooled analysis combines data from the double-blind placebo periods of the phase 2 PULSAR (NCT03496207) and phase 3 STELLAR (NCT04576988) studies. Both studies were international, multicentre, randomised, double-blind, placebo-controlled trials in patients with PAH. Efficacy and safety parameters common to both studies were analysed.</p><p><strong>Results: </strong>A total of 429 patients were randomised and treated; 237 received sotatercept and 192 received placebo. Adding sotatercept to background PAH therapy for 24 weeks improved exercise capacity (as assessed by 6-min walk distance), pulmonary vascular resistance, World Health Organization functional class, and delayed time to first occurrence of death or clinical worsening event. There were clinically important reductions in both pulmonary and right heart pressures; improvements in right ventricle (RV) size during both systole and diastole; and enhancements in RV contractility and RV-pulmonary artery coupling. The number of patients who experienced at least one adverse event of interest or special interest (increased haemoglobin, thrombocytopenia, bleeding events [mostly epistaxis], increased blood pressure, and telangiectasia) was higher in the sotatercept group than the placebo group.</p><p><strong>Discussion: </strong>This pooled analysis confirms that sotatercept delivers therapeutic benefit across a range of efficacy endpoints and has favourable safety in patients with PAH. Increased duration of follow-up will provide further insight into long-term outcomes of sotatercept in patients with PAH.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064847","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":"Initial therapy in patients with pulmonary arterial hypertension and cardiovascular comorbidities.","authors":"Athénaïs Boucly, David Montani, Fabrice Bauer, Elise Artaud-Macari, Emmanuel Bergot, Clément Boissin, Ari Chaouat, Vincent Cottin, Claire Dauphin, Bruno Degano, Pascal De Groote, Camille du Roure, Nicolas Favrolt, Delphine Horeau-Langlard, Xavier Jaïs, Mitja Jevnikar, Thomas Lacoste-Palasset, François Picard, Grégoire Prévôt, Martine Reynaud-Gaubert, Anne Roche, Ségolène Turquier, Marc Humbert, Olivier Sitbon, Laurent Savale","doi":"10.1183/13993003.00895-2024","DOIUrl":"https://doi.org/10.1183/13993003.00895-2024","url":null,"abstract":"<p><strong>Background: </strong>European guidelines recommend initial monotherapy in PAH patients with cardiovascular (CV) comorbidities based on the limited of evidence for combination therapy in this growing population.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on incident PAH patients enrolled in the French Pulmonary Hypertension Registry between 2009 and 2020. Propensity score matching was used to investigate initial dual oral combination therapy <i>versus</i> oral monotherapy in patients with at least one CV comorbidity (<i>i.e.</i>, hypertension, obesity, diabetes and coronary artery disease).</p><p><strong>Results: </strong>Of the 1784 patients identified, 1088 had ≥1 CV comorbidity, including 20% with ≥3 comorbidities. In the propensity score matched population (N=708), the majority of patients were female, with idiopathic/heritable/drug-induced PAH, at intermediate 1-year mortality risk. At first follow-up, initial dual therapy led to larger improvements in symptoms, exercise capacity, hemodynamics, and risk status than initial monotherapy, with no differences in long-term survival. Treatment discontinuations were observed in 23% of patients initiated on dual therapy and 24% of those initiated on monotherapy.</p><p><strong>Conclusions: </strong>Initial dual oral combination therapy may be beneficial and well tolerated in most PAH patients with CV comorbidities.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064848","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":"Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.","authors":"Alena Moiseenko, Anthony Sinadinos, Ana Sergijenko, Kyriel Pineault, Aarash Saleh, Konradin Nekola, Nathalie Strang, Anastasia Eleftheraki, A Christopher Boyd, Jane C Davies, Deborah R Gill, Stephen C Hyde, Gerry McLachlan, Tim Rath, Michael Rothe, Axel Schambach, Silke Hobbie, Michael Schuler, Udo Maier, Matthew J Thomas, Detlev Mennerich, Manfred Schmidt, Uta Griesenbach, Eric W F W Alton, Sebastian Kreuz","doi":"10.1183/13993003.01683-2023","DOIUrl":"10.1183/13993003.01683-2023","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR modulators offer significant improvements, but ∼10% of patients remain nonresponsive or are intolerant. This study provides an analysis of rSIV.F/HN, a lentiviral vector optimised for lung delivery, including CFTR protein expression, functional correction of CFTR defects and genomic integration site analysis in preparation for a first-in-human clinical trial.</p><p><strong>Methods: </strong>Air-liquid interface cultures of primary human bronchial epithelial cells (HBECs) from CF patients (F508del/F508del), as well as a CFTR-deficient immortalised human lung epithelial cell line mimicking class I (CFTR-null) homozygous mutations, were used to assess transduction efficiency. Quantification methods included a novel proximity ligation assay for CFTR protein expression. For assessment of CFTR channel activity, Ussing chamber studies were conducted. The safety profile was assessed using integration site analysis and <i>in vitro</i> insertional mutagenesis studies.</p><p><strong>Results: </strong>rSIV.F/HN expressed CFTR and restored CFTR-mediated chloride currents to physiological levels in primary F508del/F508del HBECs as well as in a class I cells. In contrast, the latter could not be achieved by small-molecule CFTR modulators, underscoring the potential of gene therapy for this mutation class. Combination of rSIV.F/HN-CFTR with the potentiator ivacaftor showed a greater than additive effect. The genomic integration pattern showed no site predominance (frequency of occurrence ≤10%), and a low risk of insertional mutagenesis was observed in an <i>in vitro</i> immortalisation assay.</p><p><strong>Conclusions: </strong>The results underscore rSIV.F/HN as a promising gene therapy vector for CF, providing a mutation-agnostic treatment option.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035602","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}