European Respiratory Journal最新文献

{"title":"Cystic Fibrosis Microbiome-directed Antibiotic Therapy Trial in Exacerbations Results Stratified (CFMATTERS): results of a multicentre 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":"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 multicentre two-arm parallel randomised control trial conducted across Europe/North-America enrolled 223 participants (January 2015 to 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 intravenous ceftazidime 3 g thrice daily (for allergies: aztreonam 2 g thrice daily) and tobramycin 5-10 mg·kg^-1 once daily. The \"microbiome-directed\" group received the same usual therapy plus an additional antibiotic with greatest presumed activity against the second, third and fourth most abundant genera present in the sputum microbiome, selected by a consensus expert treatment panel. The primary outcome was change in percentage of predicted forced expiratory volume in 1 s (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 <i>i.v.</i> 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 -3.9-1.7%; 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 0.60-1.38; p=0.66). The microbiome-directed group trended to have more <i>i.v.</i> days (median 42 days <i>versus</i> 28 days; p=0.08) and more subsequent exacerbations (median three <i>versus</i> two; p=0.044) the following year. There were no appreciable differences in symptom burden; however, HRQoL subscores were consistently worse in the microbiome-directed group (-4.3 points <i>versus</i> usual therapy, 95% CI -8.3--0.3 points; 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":21.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332466/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measures of OSA-specific intermittent hypoxaemia in obstructive sleep apnoea: how far is clinical routine?","authors":"Matteo Bradicich,Esther Irene Schwarz","doi":"10.1183/13993003.00399-2025","DOIUrl":"https://doi.org/10.1183/13993003.00399-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"704 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802572","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":"Hypoxic markers of severity and precision predictive outcomes in paediatric obstructive sleep apnoea: the quest must go on!","authors":"David Gozal","doi":"10.1183/13993003.00930-2025","DOIUrl":"https://doi.org/10.1183/13993003.00930-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"35 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802573","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":"Cluster analysis identifies quantitative CT imaging-based subgroups in COPD subjects with pulmonary artery enlargement.","authors":"Shelsey W Johnson, James C Ross, Pietro Nardelli, Bina Choi, Rebecca R Vanderpool, Carrie Pistenmaa, J Michael Wells, Raul San Jose Estépar, George Washko, Farbod N Rahaghi","doi":"10.1183/13993003.00038-2025","DOIUrl":"10.1183/13993003.00038-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505286","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":"Ever tried. Ever failed. No matter. The CFMATTERS study and the future of microbiome-directed trials in cystic fibrosis.","authors":"Micheál Mac Aogáin","doi":"10.1183/13993003.01122-2025","DOIUrl":"https://doi.org/10.1183/13993003.01122-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"13 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802575","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":"Tuberculosis preventive treatment in people living with HIV: to improve treatment completion, we need a simpler cascade of care.","authors":"Marcello Scopazzini,Dominik Zenner","doi":"10.1183/13993003.00638-2025","DOIUrl":"https://doi.org/10.1183/13993003.00638-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"17 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802576","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":"Reply: In support for a rational and sustainable use of in-line filters for pulmonary function tests.","authors":"Santiago C Arce,Javier C Brea Folco,Roque A Baldasaria","doi":"10.1183/13993003.01023-2025","DOIUrl":"https://doi.org/10.1183/13993003.01023-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"737 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802600","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 role of oxygen desaturation burden index in enhancing treatment strategies for childhood sleep apnoea.","authors":"Xin Zhang, Yuanyuan Li, Xueying Wu, Peipei Wang, Wei Zhang, Bingjiao Zhao, Yuehua Liu","doi":"10.1183/13993003.00553-2025","DOIUrl":"10.1183/13993003.00553-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505292","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":"Cyclic GMP-AMP synthase expression is enhanced in systemic sclerosis-associated interstitial lung disease and stimulates inflammatory myofibroblast activation.","authors":"Sheeline Yu, Buqu Hu, Ying Sun, Xue Yan Peng, Chris J Lee, Samuel Woo, John McGovern, Jana Zielonka, Tina Saber, Alexander Ghincea, Shifa Gandhi, Anjali Walia, Taylor Pivarnik, Genta Ishikawa, Shuai Shao, Huanxing Sun, Baran Ilayda Gunes, Sophia Kujawski, Stephanie Perez, William Odell, Monique Hinchcliff, John Varga, Carol Feghali-Bostwick, Maor Sauler, Jose L Gomez, Changwan Ryu, Erica L Herzog","doi":"10.1183/13993003.01564-2024","DOIUrl":"10.1183/13993003.01564-2024","url":null,"abstract":"<p><strong>Objective: </strong>The lungs of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) contain inflammatory myofibroblasts that arise in association with fibrotic stimuli and perturbed innate immunity. The cytosolic DNA-binding receptor cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity and therapeutic potential in SSc-ILD using human biospecimens, cultured fibroblasts, precision-cut lung slices and a well-accepted animal model.</p><p><strong>Methods: </strong>Expression and localisation of cGAS, cytokines and type 1 interferons were evaluated in SSc‑ILD lung tissues, bronchoalveolar lavage fluid and isolated lung fibroblasts. <i>CGAS</i> activation was assessed in a publicly available SSc-ILD single-cell RNA-sequencing dataset. Production of cytokines, type 1 interferons and α-smooth muscle actin elicited by transforming growth factor-β1 or local substrate stiffness was measured in normal human lung fibroblasts <i>via</i> quantitative reverse transcription PCR, ELISA and immunofluorescence. Small molecule cGAS inhibition was tested in cultured fibroblasts, human precision-cut lung slices and the bleomycin pulmonary fibrosis model.</p><p><strong>Results: </strong>SSc-ILD lung tissue and bronchoalveolar lavage fluid were enriched for cGAS, cytokines and type 1 interferons. The cGAS pathway showed constitutive activation in SSc-ILD fibroblasts and was inducible in normal human lung fibroblasts by transforming growth factor-β1 or mechanical stimuli. In these settings, and in precision-cut lung slices, cGAS expression was paralleled by the production of cytokines, type 1 interferons and α-smooth muscle actin, which was mitigated by a small molecule cGAS inhibitor. These findings were recapitulated in the bleomycin mouse model.</p><p><strong>Conclusion: </strong>cGAS signalling contributes to pathogenic inflammatory myofibroblast phenotypes in SSc‑ILD. Inhibiting cGAS or its downstream effectors represents a novel therapeutic approach.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077043","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":"Renal function dynamics in pulmonary hypertension trials: less than anticipated.","authors":"Lars Harbaum,Thenappan Thenappan","doi":"10.1183/13993003.01042-2025","DOIUrl":"https://doi.org/10.1183/13993003.01042-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"113 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802571","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}