European Respiratory Journal最新文献

{"title":"Rejuvenation as a future for pulmonary fibrosis.","authors":"Panagiota Tsiri, Bruno Crestani","doi":"10.1183/13993003.00640-2025","DOIUrl":"https://doi.org/10.1183/13993003.00640-2025","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":"144233667","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":"Screening relatives of familial pulmonary fibrosis patients: who, when, how and why?","authors":"Raphael Borie, Jonathan A Kropski","doi":"10.1183/13993003.00019-2025","DOIUrl":"10.1183/13993003.00019-2025","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":"144233669","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":"Building translational bridges in idiopathic pulmonary fibrosis research: from epithelial dysfunction to dysregulated macrophage polarisation and fibrogenesis.","authors":"Panagiota Tsiri, Guillaume Beltramo, Martin Kolb, Bruno Crestani","doi":"10.1183/13993003.00938-2025","DOIUrl":"https://doi.org/10.1183/13993003.00938-2025","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":"144233661","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":"Climbing the hierarchy of evidence in interstitial lung disease transcriptomics.","authors":"Liam P Coyne, Auyon J Ghosh","doi":"10.1183/13993003.02471-2024","DOIUrl":"https://doi.org/10.1183/13993003.02471-2024","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":"144233664","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":"YAP/TAZ are crucial regulators of macrophage-mediated pulmonary inflammation and fibrosis after bleomycin-induced injury.","authors":"Masum M Mia, Siti Aishah Binte Abdul Ghani, Dasan Mary Cibi, Hanumakumar Bogireddi, Uthayanan Nilanthi, Ashwatthaman Selvan, Wai Shiu Fred Wong, Manvendra K Singh","doi":"10.1183/13993003.01544-2023","DOIUrl":"10.1183/13993003.01544-2023","url":null,"abstract":"<p><p>Pulmonary fibrosis is the most prevalent and severe form of end-stage interstitial lung disease. Macrophages are crucial players in inflammation-induced pulmonary fibrosis, but the mechanisms driving macrophage polarisation and their specific roles in pulmonary fibrosis pathogenesis remain poorly understood. Here, we demonstrate that both YAP and TAZ are activated in lung macrophages from patients with pulmonary fibrosis as well as in mice with bleomycin-induced pulmonary fibrosis. Myeloid-specific <i>Yap/Taz</i> deletion resulted in reduced recruitment of monocyte-derived alveolar macrophages (Mo-AMs), impaired inflammatory responses, decreased pulmonary fibrosis and enhanced alveolar epithelial cell regeneration following bleomycin treatment. Conversely, the expression of a constitutively active YAP mutant (YAP^5SA) exacerbated bleomycin-induced pulmonary fibrosis by increasing Mo-AM recruitment, elevating expression of pro-inflammatory and pro-fibrotic markers, and impairing alveolar epithelial cell regeneration. We demonstrate that YAP/TAZ-CCL2 (C-C motif chemokine ligand 2) signalling plays a crucial role in bleomycin-induced pulmonary fibrosis, as blocking CCL2 with a neutralising antibody effectively abrogated the YAP^5SA-induced recruitment of Mo-AMs, inflammatory and fibrotic responses. Additionally, we reveal that the YAP/TAZ-MBD2-TGFβ1-pSMAD2 signalling axis is crucial not only for pro-fibrotic macrophage polarisation, but also for their cross-talk with lung fibroblasts, driving the fibroblast-to-myofibroblast transition. Collectively, these findings suggest that targeting aberrant YAP/TAZ activity to modulate inflammatory and fibrotic response could be a promising strategy for the prevention and treatment of pulmonary fibrosis.</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/PMC12138047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364103","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":"Protein biomarkers of interstitial lung abnormalities in relatives of patients with pulmonary fibrosis.","authors":"Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake","doi":"10.1183/13993003.01349-2024","DOIUrl":"10.1183/13993003.01349-2024","url":null,"abstract":"<p><strong>Rationale: </strong>First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.</p><p><strong>Methods: </strong>Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.</p><p><strong>Results: </strong>Of 237 relatives from two independent cohorts, 26% had ILA. Seven proteins were associated with ILA in the discovery cohort after false discovery rate adjustment, and all remained significant after adjusting for age, gender and smoking status. Six of the seven proteins were significantly associated in the validation cohort, including growth differentiation factor 15, surfactant protein D and surfactant protein B. In a multivariable model, six proteins combined with basic demographics in the discovery cohort had an area under the curve of 0.92 (0.88 in the validation cohort). Least absolute shrinkage and selection operator modelling identified three proteins and age as predictors, with an area under the curve of 0.89 in the validation cohort. When applied to the combined cohorts, this simple model would reduce the need for computed tomography imaging in one of every three relatives screened.</p><p><strong>Conclusion: </strong>Peripheral blood proteins are associated with ILA in relatives of patients with pulmonary fibrosis and can be used to detect them. Our findings demonstrate the potential use of blood biomarkers in this high-risk group and suggest molecular targets for future investigation.</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/PMC12138028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064850","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":"<i>ERJ</i> Podcast May 2025: Efficacy and safety of the activin signalling inhibitor sotatercept.","authors":"","doi":"10.1183/13993003.E6505-2025","DOIUrl":"https://doi.org/10.1183/13993003.E6505-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"65 5","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157626","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":"Are systemic corticosteroids needed for all asthma exacerbations?","authors":"William W Busse,Paul M O'Byrne","doi":"10.1183/13993003.00370-2025","DOIUrl":"https://doi.org/10.1183/13993003.00370-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"33 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122032","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":"Particulate matter-related ITIH4 deficiency is associated with an emphysema phenotype of chronic obstructive pulmonary disease through JNK-dependent and JNK-independent signaling.","authors":"Sheng-Ming Wu,Kuan-Yuan Chen,Hsiao-Chi Chuang,Shu-Chuan Ho,Cheng-Wei Lin,Chia-Li Han,Wei-Lun Sun,Po-Hao Feng,Shiou-Fu Lin,Yueh-Hsi Chen,Tzu-Tao Chen,Chien-Hua Tseng,Wen-Te Liu,Kang-Yun Lee","doi":"10.1183/13993003.01610-2024","DOIUrl":"https://doi.org/10.1183/13993003.01610-2024","url":null,"abstract":"RATIONALE: Prolonged exposure to airborne particulate matter (PM) is associated with emphysema and chronic obstructive pulmonary disease (COPD); however, the precise underlying mechanism remains unclear.OBJECTIVESIn a previous high-throughput screen, we identified inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) as a biomarker of long-term PM exposure. We hypothesized that ITIH4 is implicated in PM-related emphysema.METHODSWe investigated the association between ITIH4 expression and ambient PM exposure through a clinical cohort analysis (220 patients with COPD and 61 healthy participants) and in vitro studies.MEASUREMENTS AND MAIN RESULTSThe COPD cohort studies revealed significant correlations between emphysema severity, ambient PM exposure, and serum ITIH4 levels. In primary small airway epithelial cells from COPD patients with low basal levels of ITIH4, exposure to PM and oxidative stress led to increased apoptosis. However, ITIH4 overexpression significantly inhibited oxidative stress-induced apoptosis in normal and COPD airway epithelial cells. Acute exposure to hydrogen peroxide resulted in the rapid degradation of ITIH4 protein with no effect on transcriptional level, although ITIH4 gene expression is downregulated in the lung tissue of patients with COPD. A human apoptosis antibody array revealed that ITIH4 overexpression attenuated hydrogen peroxide-induced apoptotic signaling. Furthermore, extracellular ITIH4 protein confers cytoprotective functions in cells exposed to PM or oxidative stress. Mechanistically, ITIH4 attenuated oxidative stress-induced JNK activation and β-catenin decrease. A deficiency of ITIH4 exacerbated the effects of oxidative stress.CONCLUSIONSWe identified a novel pathogenetic mechanism involving ITIH4, where chronic exposure to air pollution induces or promotes emphysema.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"57 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122053","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":"Renal dysfunction and outcomes in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: an individual participant data meta-analysis.","authors":"Amber Meservey,Nadine Al-Naamani,Jasleen Minhas,Jason S Fritz,Dina Appleby,Guillaume Baudry,Nicolas Girerd,Rui Feng,Steven M Kawut,Jude Moutchia","doi":"10.1183/13993003.02400-2024","DOIUrl":"https://doi.org/10.1183/13993003.02400-2024","url":null,"abstract":"BACKGROUNDPulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction with extrapulmonary sequalae including renal dysfunction. We sought to characterize renal dysfunction in PAH and CTEPH and to assess the effect of pulmonary hypertension treatment on renal function.METHODSWe performed an individual participant data meta-analysis of 6694 participants from 18 phase III randomized clinical trials of pulmonary hypertension therapies. We calculated estimated glomerular filtration rate (eGFR) using the race-agnostic 2021 CKD-EPI equation.RESULTSThe mean age was 49.6±15.5 years, 78% were female and 58% had idiopathic PAH. A total of 907 participants (13.5%) had a baseline eGFR<60 mL·min-1·1.73 m-2. Lower baseline eGFR correlated with higher mean right atrial pressure (mRAP) and lower cardiac index. At 12-16 weeks, a 10 mmHg decrease in mRAP from baseline or a 1 L·min-1·m-2 increase in cardiac index was associated with only a 1.7 mL·min-1·1.73 m-2 (95% CI: -2.9, -0.5; p=0.006) or a 1.4 mL·min-1·1.73 m-2 (95% CI: 0.5, 2.4; p=0.003) increase in eGFR, respectively. A 10 mL·min-1·1.73 m-2 lower baseline eGFR was associated with an increased risk of all-cause mortality (aHR: 1.16 [95% CI:1.08, 1.23]; p<0.001). Interestingly, pulmonary hypertension treatment was associated with only a small improvement in eGFR at 12-16 weeks (aβ: 2.0 mL·min-1·1.73 m-2 [95% CI: 1.4, 2.6]; p<0.001).CONCLUSIONRenal dysfunction remains highly prevalent in PAH and CTEPH and is associated with worse hemodynamics and worse clinical outcomes. In this cohort with relatively preserved renal function, pulmonary hypertension treatment was associated with only a minimal improvement in eGFR.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"60 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122127","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}