European Respiratory Journal最新文献

{"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}

{"title":"Genome-wide association study reveals <i>CBX7</i> as a novel susceptibility gene associated with primary spontaneous pneumothorax in the Chinese Han population.","authors":"Leilei Xu, Dehua Ma, Bingjian Wang, Mengru Cai, Zhichong Wu, Shuwen Cheng, Minghui Cai, Yibing Ding, Xinxin Zhang, Qi Sun, Fengnan Niu, Hongyan Wu, Zhicheng Dai, Haiyan Min, Yanting Wen, Shiyu Song, Wei Zou, Chao Wang, Sufen Li, Jiaochen Wang, Jianfei Shen, Xinxin Wang, Aifen Lin, Xingbing Cao, Xinxin Yuan, Chao Xia, Zhongying Guo, Zhenhua Feng, Ronghui Du, Jun Qiao, Qi Gao, Benlong Shi, Saihu Mao, Tianming Chen, Haozhen Ren, Minhua Ye, Xiaowen Hu, Ping Hu, Zhengfeng Xu, Shilin Chen, Yong Qiu, Yong Wang, Qian Gao, Chengchu Zhu, Zezhang Zhu, Long Yi","doi":"10.1183/13993003.02110-2024","DOIUrl":"https://doi.org/10.1183/13993003.02110-2024","url":null,"abstract":"<p><strong>Background: </strong>Primary spontaneous pneumothorax is a rare disease commonly found in young adults with unknown etiology. We aimed to investigate the susceptibility genes and the downstream signaling involved in the development of primary spontaneous pneumothorax.</p><p><strong>Methods: </strong>We conducted the first large-scale genome-wide association study (GWAS) composed of 2223 patients and 3838 controls. The functional role of the novel susceptibility loci was investigated by both in-vivo and in-vitro assays. Gene expression profiling in lung epithelial cell lines was performed and conditional gene knockout mice were generated.</p><p><strong>Results: </strong>We identified four novel susceptibility loci at 14q32.2 near <i>C14orf177</i>, at 15q26.3 near <i>CHSY1</i>, at 16q23.1 near <i>CFDP1</i>, and at 22q13.1 near <i>CBX7</i>. The fine-mapping of 22q13.1 revealed a functional variant which regulated <i>CBX7</i> expression by disrupting the binding activity of transcription factor CREB1. Conditional knock-out of <i>Cbx7</i> in mouse lung epithelial cells resulted in lung cyst formation. Meanwhile, down-regulation of the <i>CBX7</i> elevated the expression of <i>MMP9</i> and <i>MMP16</i>, which are part of extracellular matrix regulators and may lead to lung injury.</p><p><strong>Conclusions: </strong>Our GWAS discovered four novel susceptibility loci of primary spontaneous pneumothorax and presented a mechanistic basis for the genetic association with primary spontaneous pneumothorax. The novel susceptibility gene <i>CBX7</i> and downstream <i>MMPs</i> signaling give a new clue to the pathogenesis of primary spontaneous pneumothorax.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233658","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":"Clarification of author disclosures in the article \"Angiotensin converting enzyme 2 and angiotensin (1-7) axis in pulmonary arterial hypertension\".","authors":"","doi":"10.1183/13993003.52416-2019","DOIUrl":"https://doi.org/10.1183/13993003.52416-2019","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":"144233663","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":"Targeting the AXL pathway: a promising strategy for pulmonary fibrosis.","authors":"Jennifer L Larson-Casey, A Brent Carter","doi":"10.1183/13993003.00114-2025","DOIUrl":"https://doi.org/10.1183/13993003.00114-2025","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":"144233671","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: Spirometry remains the GOLD standard test for COPD diagnosis.","authors":"Dave Singh, Alvar Agusti, Claus Volgelmeier, David Halpin","doi":"10.1183/13993003.00794-2025","DOIUrl":"10.1183/13993003.00794-2025","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233668","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":"Accelerated epigenetic ageing 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":"10.1183/13993003.01618-2024","url":null,"abstract":"<p><strong>Background: </strong>The role of epigenetic ageing in the environmental pathogenesis and prognosis of fibrotic interstitial lung disease (fILD) is unclear. We evaluated whether ambient particulate matter with diameter ≤2.5 μm (PM_2.5) and neighbourhood disadvantage exposures are associated with accelerated epigenetic ageing, 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). 5-year PM_2.5 exposures were estimated using satellite-derived hybrid models. Neighbourhood disadvantage was calculated using US 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) increase in PM_2.5 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 (hazard ratio 1.17 per 1-year increase in EAD, 95% CI 1.10-1.24; p<0.001), with EAD mediating 40% of the PM_2.5-survival relationship and 59% of the neighbourhood disadvantage-survival relationship. 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":"2025-06-05","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":"Rbms1 promotes pulmonary fibrosis by stabilising Sumo2 mRNA to facilitate Smad4-SUMOylation and fibroblast activation.","authors":"Yingying Guo, Qianqian Wang, Yuhan Zhang, Lingxue Ren, Yuquan Wang, Yang Liu, Miao Liu, Xiaomu Tian, Qiudi Liu, Yi Chen, Jian Sun, Tongzhu Jin, Xinyue Wang, Yanbo Wang, Tianyu Li, Yuhong Zhou, Zhixin Li, Yunyan Gu, Baofeng Yang, Haihai Liang","doi":"10.1183/13993003.01667-2024","DOIUrl":"https://doi.org/10.1183/13993003.01667-2024","url":null,"abstract":"<p><p>The formation of myofibroblast foci constitutes a hallmark pathological feature of idiopathic pulmonary fibrosis (IPF), yet the mechanism remains elusive. RNA binding motif single-stranded interacting protein 1 (RBMS1), is known to be essential for proliferation and cell cycle progression; however, its role in pulmonary fibrosis remains to be clarified.This study aimed to systematically elucidate the role and underlying mechanism of RBMS1 in pulmonary fibrosis utilising mouse primary lung fibroblasts (mPLFs), fibroblast-specific Rbms1 deletion and overexpression mice models, and lung samples from IPF patients.RBMS1 was highly expressed in both IPF patient lungs and murine bleomycin (BLM)-induced fibrotic lesions. Notably, elevated RBMS1 expression was observed in the cytoplasm of mPLFs following TGF-β1 stimulation. Rbms1 promoted lung fibroblast activation, while knockdown of Rbms1 mitigated TGF-β1-induced fibrogenesis. <i>In vivo</i>, overexpression impaired lung function and exacerbated pulmonary fibrosis, whereas fibroblast-specific Rbms1 deletion exhibited a significant reduction in fibrosis post-BLM treatment. Mechanistically, Rbms1 binds to Sumo2 3'UTR, enhancing the mRNA stability. Furthermore, Rbms1 induced the SUMOylation of Smad4, with lysine 158 identified as a critical SUMOylation site. Meanwhile, Sumo2 knockdown alleviated the Rbms1-driven exacerbation of pulmonary fibrosis. Importantly, the nortriptyline pharmacologically inhibited RBMS1 to ameliorate pulmonary fibrosis in mice.Collectively, our study sheds light on the regulatory role of RBMS1 in pulmonary fibrosis, highlighting its therapeutic potential for targeted antifibrotic strategies.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233660","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}