European Respiratory Journal最新文献

{"title":"How systemic antibodies prevent severe respiratory infections in COPD: A Viewpoint.","authors":"Carl Persson","doi":"10.1183/13993003.00896-2025","DOIUrl":"https://doi.org/10.1183/13993003.00896-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"44 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328588","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":"Mannose-6-phosphate attenuates acute lung injury by competitive release of acid sphingomyelinase from the mannose-6-phosphate receptor in endothelial caveolae.","authors":"Tian Jiang, Rudi Samapati, Sergej Klassen, Supandi Winoto-Morbach, Zain H Mohamed, Rolf Göggel, Jun Yin, Lijie Tan, Christoph Arenz, Sabrina Schulz, Lasti Erfinanda, Robert Preissner, Szandor Simmons, Stefan Schütze, Stefan Uhlig, Wolfgang M Kuebler","doi":"10.1183/13993003.00003-2024","DOIUrl":"10.1183/13993003.00003-2024","url":null,"abstract":"<p><strong>Background: </strong>Platelet-activating factor (PAF)-induced pulmonary endothelial barrier failure is mediated by acid sphingomyelinase (ASM) translocation to caveolae. ASM, however, lacks a transmembrane domain for anchoring inside caveolae. We hypothesised that ASM anchors to cation-independent mannose-6-phosphate (M6P) receptor (CI-M6PR) in caveolae, from where it can be competitively released by M6P.</p><p><strong>Methods: </strong>We explored ASM-CI-M6PR interactions using co-immunoprecipitation and proximity ligation assay in isolated lungs and human pulmonary microvascular endothelial cells. ASM release by M6P was determined in human pulmonary microvascular endothelial cells, isolated lungs and <i>in vivo</i>. The effects of M6P on 1) PAF-induced lung oedema formation and endothelial Ca²⁺ concentration and 2) lung injury in acid instilled, overventilated mouse lungs were examined. ASM levels were measured in serum and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. The TriNetX database was probed for associations of ASM-inhibiting tricyclic antidepressants with outcomes.</p><p><strong>Results: </strong>Co-immunoprecipitation and proximity ligation assay revealed an ASM interaction with CI-M6PR in endothelial caveolae, which was further increased by PAF. M6P, but not glucose-6-phosphate, caused ASM release, thereby decreasing ASM content and activity in caveolae <i>in vitro</i>, <i>in situ</i> and <i>in vivo</i>. Analogously, M6P, yet not glucose-6-phosphate, attenuated PAF-induced endothelial Ca²⁺ influx and lung oedema <i>in situ</i>, and acute lung injury <i>in vivo</i>. ASM levels were increased in serum but not bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome. Use of tricyclic antidepressants was associated with better outcomes in patients with severe respiratory infections.</p><p><strong>Conclusions: </strong>CI-M6PR anchors ASM in caveolae. M6P may hence present a promising target in ASM-related lung injury and oedema.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523009","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":"Cystic Fibrosis Microbiome-directed Antibiotic Therapy Trial in Exacerbations Results Stratified (CFMATTERS): Results of a multi-centre randomised controlled trial.","authors":"Barry J Plant, Gisli G Einarsson, Kevin F Deasy, Darren Dahly, Pradeep K Singh, Peter J Barry, Christopher H Goss, Isabelle Fajac, Tamara Vagg, Isabelle Durieu, Evelyn Flanagan, Grace O'Callaghan, Clémence Martin, Pierre-Régis Burgel, Charles S Haworth, R Andres Floto, Damian G Downey, Lieven J Dupont, Andrew M Jones, J Stuart Elborn, Joseph A Eustace, Marcus A Mall, Michael M Tunney","doi":"10.1183/13993003.02443-2024","DOIUrl":"https://doi.org/10.1183/13993003.02443-2024","url":null,"abstract":"<p><strong>Background: </strong>This study explores the effectiveness and safety of microbiome-directed-antimicrobial-therapy <i>versus</i> usual-antimicrobial-therapy in adult cystic fibrosis pulmonary exacerbations.</p><p><strong>Methods: </strong>A multi-centre two-arm parallel randomised control trial conducted across Europe/North-America enrolled 223 participants (January 2015 - August 2017). All participants were chronically colonised with <i>Pseudomonas aeruginosa</i> and were randomised 1:1 into two study-arms. The \"usual-therapy group\" received 2-weeks of IV ceftazidime 3g thrice-daily (for allergies: aztreonam 2g thrice-daily) and tobramycin 5-10mg·kg^-1 once-daily. The \"microbiome-directed group\" received the same usual-therapy plus an additional antibiotic with greatest presumed activity against the 2nd, 3rd and 4th most abundant genera present in the sputum microbiome, selected by a Consensus Expert Treatment Panel. The primary outcome was change in percentage of predicted FEV₁ (ppFEV₁) at 14 days post initiation of antibiotics. Secondary outcomes examined ppFEV₁ at 7 days, 28 days, and 3 months; time-to-next exacerbation; symptom burden at 7 days; Health Related Quality of Life (HRQoL) at 28 days; and number of exacerbations and IV antibiotic days at 12 months.</p><p><strong>Results: </strong>149 participants had an eligible exacerbation (usual-therapy n=83, microbiome-directed therapy n=66). There was no difference between the groups for ppFEV₁ at day 14 (-1.1%, 95%CI -3.9 to 1.7; p=0.46), or ppFEV₁ measured at other time-points, or for time-to-next exacerbation (microbiome-directed <i>versus</i> usual-therapy Hazard Ratio 0.91 [95%CI 0.60 to 1.38; p=0.66]). The microbiome-directed group trended to have more IV days (median 42 <i>versus</i> 28; p=0.08) and more subsequent exacerbations (median 3 <i>versus</i> 2; p=0.044) the following year. There were no appreciable differences in symptom burden; however, HRQoL sub-scores were consistently worse in the microbiome-directed group (-4.3 points <i>versus</i> usual therapy (95%CI -8.3 to -0.3, p=0.033).</p><p><strong>Conclusion: </strong>The addition of a third antibiotic based on sputum microbiome sequencing analysis did not result in improved clinical outcomes.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283157","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":"Early-life exposure to mixture of phenols and respiratory health in pre-school children.","authors":"Alicia Guillien, Sam Bayat, Inès Amine, Anne Boudier, Sarah Lyon-Caen, Joane Quentin, Zoltán Hantos, Séverine Valmary-Degano, Amrit K Sakhi, Cathrine Thomsen, Claire Philippat, Rémy Slama, Valérie Siroux","doi":"10.1183/13993003.02265-2024","DOIUrl":"https://doi.org/10.1183/13993003.02265-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Exposure to synthetic phenols is suspected of affecting child respiratory health, but epidemiological findings are not consistent and studies on exposure during infancy are lacking. We aimed to investigate the association between exposure to a mixture of phenols in pregnancy and in infancy and children's respiratory health.</p><p><strong>Methods: </strong>Among 363 mother-child pairs from the SEPAGES cohort, twelve phenols were measured in weekly-pooled urine samples collected twice during pregnancy (second (T2) and third (T3) trimesters) and in infancy (2 months (M2) and 1 year (Y1)). Children's lung function was assessed through tidal breathing flow-volume loops and nitrogen multiple-breath washout at M2, and standard and intra-breath oscillometry at 3 years. Time-specific phenol exposure profiles were identified through cluster analysis and then studied in association with respiratory health using adjusted regression models.</p><p><strong>Results: </strong>Two exposure profiles were identified at each point in time, characterized by low <i>versus</i> high levels of several phenol compounds. Overall, high exposure profiles were associated with altered oscillometry parameters at 3 years, particularly between high exposure profile at T2 and higher frequency-dependence of resistance (R7-19) and lower volume-dependence of reactance (ΔX); high exposure profile at M2 and lower reactance at 7 Hz (X7), and high exposure at Y1 and higher area of the reactance curve (AX), resistance at 7 Hz (R7), and volume-dependence of resistance (ΔR).</p><p><strong>Conclusion: </strong>This study relying on repeated and accurate assessments of phenols exposure provides evidence of the deleterious effects of early-life exposures to a mixture of phenols on lung function in pre-school children.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283158","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":"Distinct mural cells and fibroblasts promote pathogenic plasma cell accumulation in idiopathic pulmonary fibrosis.","authors":"Zhi Yang, Gaoyuan Cao, Xiaosheng Tan, Sarah Orfanos, Joseph Jude, Gaetan Barbet, Steven S An, Dianhua Jiang, Reynold A Panettieri, Qi Yang","doi":"10.1183/13993003.01114-2024","DOIUrl":"10.1183/13993003.01114-2024","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is characterised by significant but poorly understood immune and antibody responses. This study examines the spatial transcriptomes and microenvironmental niches of antibody-producing plasma cells and tertiary lymphoid structures in IPF lungs, and the molecular pathways influencing antibody accumulation and pulmonary fibrosis.</p><p><strong>Methods: </strong>Explant lung tissues from IPF patients and control normal lungs were used for spatial transcriptome assays and validating RNAscope and immunofluorescence assays. Fibroblasts derived from IPF and control lungs were examined for their ability to attract plasma cells. Neutralising antibodies were administered to investigate molecules affecting pulmonary plasma cell accumulation and fibrosis in bleomycin-treated mice.</p><p><strong>Results: </strong>Human IPF lungs exhibited a remarkably widespread distribution of plasma cells and local antibodies in the fibrotic regions, disseminating from plasma cell-generating tertiary lymphoid structures. Novel mural cells wrapped the vessels in tertiary lymphoid structure regions, expressing C-C motif chemokine receptor 7 (CCR7) ligands that attracted T-cells into tertiary lymphoid structures to promote plasma cell generation. Distinct IPF-associated fibroblasts further secreted C-X-C motif chemokine ligand 12 (CXCL12), providing an extramedullary niche to foster the dissemination and accumulation of plasma cells in the fibrotic regions. Neutralisation of CCR7 ligands or CXCL12 reduced plasma cell and local antibody accumulation in the lungs of bleomycin-treated mice, leading to reduced transforming growth factor β concentrations and alleviated pulmonary fibrosis.</p><p><strong>Conclusions: </strong>Plasma cells and local antibodies are widely distributed in the fibrotic regions of IPF lungs. Distinct subsets of IPF-associated mural cells and fibroblasts promote pathological plasma cell and antibody accumulation. These findings have potential implications for strategies aimed at targeting immune and antibody responses to combat IPF.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467593","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":"Clarification of author disclosures for four <i>ERJ</i> articles.","authors":"","doi":"10.1183/13993003.50414-2020","DOIUrl":"https://doi.org/10.1183/13993003.50414-2020","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233662","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":"Small packages but big insights: extracellular vesicles as biomarkers in interstitial lung disease associated with systemic sclerosis.","authors":"Olivier Burgy, Mareike Lehmann","doi":"10.1183/13993003.02529-2024","DOIUrl":"https://doi.org/10.1183/13993003.02529-2024","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233670","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":"Is it time to use pre-bronchodilator spirometry to rule out COPD?","authors":"Panaiotis Finamore, Claudio Pedone, Simone Scarlata, Davide Fontana, Anna Zito, Raffaele Antonelli Incalzi","doi":"10.1183/13993003.00386-2025","DOIUrl":"https://doi.org/10.1183/13993003.00386-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233665","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":"Transcriptomics of interstitial lung disease: a systematic review and meta-analysis.","authors":"Daniel He, Sabina A Guler, Casey P Shannon, Christopher J Ryerson, Scott J Tebbutt","doi":"10.1183/13993003.01070-2024","DOIUrl":"10.1183/13993003.01070-2024","url":null,"abstract":"<p><strong>Objective: </strong>Gene expression (transcriptomics) studies have revealed potential mechanisms of interstitial lung disease, yet sample sizes of studies are often limited and between-subtype comparisons are scarce. The aim of this study was to identify and validate consensus transcriptomic signatures of interstitial lung disease subtypes.</p><p><strong>Methods: </strong>We performed a systematic review and meta-analysis of fibrotic interstitial lung disease transcriptomics studies using an individual participant data approach. We included studies examining bulk transcriptomics of human adult interstitial lung disease samples and excluded those focusing on individual cell populations. Patient-level data and expression matrices were extracted from 43 studies and integrated using a multivariable integrative algorithm to develop interstitial lung disease classification models.</p><p><strong>Results: </strong>Using 1459 samples from 24 studies, we identified transcriptomic signatures for idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, idiopathic nonspecific interstitial pneumonia and systemic sclerosis-associated interstitial lung disease against control samples, which were validated on 308 samples from eight studies (idiopathic pulmonary fibrosis area under receiver operating curve (AUC) 0.99, 95% CI 0.99-1.00; hypersensitivity pneumonitis AUC 0.91, 95% CI 0.84-0.99; nonspecific interstitial pneumonia AUC 0.94, 95% CI 0.88-0.99; systemic sclerosis-associated interstitial lung disease AUC 0.98, 95% CI 0.93-1.00). Significantly, meta-analysis allowed us to identify, for the first time, robust lung transcriptomics signatures to discriminate idiopathic pulmonary fibrosis (AUC 0.71, 95% CI 0.63-0.79) and hypersensitivity pneumonitis (AUC 0.76, 95% CI 0.63-0.89) from other fibrotic interstitial lung disease, and unsupervised learning algorithms identified putative molecular endotypes of interstitial lung disease associated with decreased forced vital capacity and diffusing capacity of the lungs for carbon monoxide % predicted. Transcriptomics signatures were reflective of both cell-specific and disease-specific changes in gene expression.</p><p><strong>Conclusion: </strong>We present the first systematic review and largest meta-analysis of fibrotic interstitial lung disease transcriptomics to date, identifying reproducible transcriptomic signatures with clinical relevance.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738955","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":"Yapping about macrophages in fibrotic lung disease.","authors":"Robert Lafyatis, Eleanor Valenzi","doi":"10.1183/13993003.00075-2025","DOIUrl":"https://doi.org/10.1183/13993003.00075-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233673","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}