European Respiratory Journal最新文献

{"title":"ERJ Podcast September 2025: Neutrophil-derived biomarkers in bronchiectasis.","authors":"","doi":"10.1183/13993003.e6603-2025","DOIUrl":"https://doi.org/10.1183/13993003.e6603-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"47 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140048","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":"Pulmonary hypertension in COPD exacerbation: a transient storm with long-term consequences?","authors":"Omer Faruk Uysal,John R Hurst","doi":"10.1183/13993003.01508-2025","DOIUrl":"https://doi.org/10.1183/13993003.01508-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"64 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140310","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":"A cautionary note on the naive use of general-population biobanks to study pulmonary arterial hypertension, with a focus on Mendelian randomization.","authors":"Benjamin Woolf,Eckart De Bie,Vallerie McLaughlin,Stefan Gräf,Mark Toshner,Martin R Wilkins,Christopher J Rhodes,Stephen Burgess","doi":"10.1183/13993003.00436-2025","DOIUrl":"https://doi.org/10.1183/13993003.00436-2025","url":null,"abstract":"","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"10 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083422","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":"Placebo effect on brainstem activity associated with capsaicin-evoked urge-to-cough in healthy humans.","authors":"Aung Aung Kywe Moe,Tara G Bautista,Jennifer Leech,Stuart B Mazzone,Michael J Farrell","doi":"10.1183/13993003.00645-2025","DOIUrl":"https://doi.org/10.1183/13993003.00645-2025","url":null,"abstract":"BACKGROUNDPlacebo effects are common in studies of cough and antitussive medications, suggestive of a profound influence of brain activity over cough neural processing. We previously reported placebo intervention-associated reductions in the urge-to-cough and the associated higher order brain network activity evoked by capsaicin inhalation, an effect involving increased activation of the prefrontal cortex.OBJECTIVEIn this study, we set out to advance the understanding of placebo antitussive brain circuitry by testing the hypothesis that the activity of brainstem nuclei during capsaicin inhalation will similarly be altered by placebo intervention.METHODSUsing an expectation-dependent placebo induction design during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) optimised for quantifying brainstem activity, we compared regional brainstem responses evoked by capsaicin inhalation in sixteen healthy individuals during No Intervention versus Placebo Intervention trials.RESULTSCapsaicin-induced urge-to-cough subjective ratings were significantly lower during the Placebo Intervention trials than No Intervention trials. Placebo Intervention resulted in a significant reduction in capsaicin-induced BOLD signal activation across many brainstem nuclei including the medullary brainstem sites where airway vagal sensory neurons are known to terminate.CONCLUSIONThese data confirm the inhibitory effects of placebo intervention on capsaicin-evoked urge-to-cough and suggest the existence of a \"top-down\" brain circuit controlling cough sensory neural processing at the level of the brainstem during placebo conditions.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"29 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083434","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":"Changes in Sputum Viscoelastic Properties and Airway Inflammation in Primary Ciliary Dyskinesia are Comparable to Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor Therapy.","authors":"Hannah Nussstein,Ruth M Urbantat,Kerstin Fentker,Aditi Loewe,Julia Duerr,Mohamed Haji,Felix Doellinger,Mirjam Stahl,Simon Y Graeber,Michael Gradzielski,Jobst Röhmel,Philipp Mertins,Laura Schaupp,Marcus A Mall","doi":"10.1183/13993003.00616-2025","DOIUrl":"https://doi.org/10.1183/13993003.00616-2025","url":null,"abstract":"BACKGROUNDPrimary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are muco-obstructive lung diseases that are caused by distinct genetically determined defects in mucociliary clearance, however, knowledge on the relative severity of airway mucus dysfunction and chronic inflammation remains limited. The aim of this study was therefore to compare sputum viscoelastic properties, inflammation markers and the proteome between patients with PCD and patients with CF before and under elexacaftor/tezacaftor/ivacaftor (ETI) therapy.METHODSWe compared sputum rheology, inflammation markers and the proteome in 42 clinically stable adolescent and adult patients with PCD, 40 patients with CF with at least one F508del allele before (baseline) and 3 months after initiation of ETI and 15 age-matched healthy controls.RESULTSThe elastic modulus (G') and viscous modulus (G″) of PCD sputum was increased compared to healthy controls (p<0.001), lower than in CF at baseline (p<0.001) and similar to CF on ETI. Inflammation markers in PCD sputum including neutrophil elastase (NE), free DNA, myeloperoxidase (MPO), interleukin (IL)-1β and IL-8 were also increased compared to healthy controls (all p<0.001), lower than in CF at baseline (p<0.05 to p<0.001) and comparable to CF on ETI. Similar, changes in the sputum proteome were less pronounced in PCD compared to CF at baseline, but comparable between PCD and CF on ETI.CONCLUSIONSClinically stable patients with PCD show changes in sputum viscoelastic properties, inflammation markers and the proteome that are less severe than in patients with CF at baseline, but comparable to CF patients on ETI therapy.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"1 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083339","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":"Two randomized controlled Phase 2 studies of the oral neutrophil elastase inhibitor alvelestat in alpha-1 antitrypsin deficiency.","authors":"J Michael Wells,Ingrid L Titlestad,Hanan Tanash,Alice M Turner,Kenneth R Chapman,Umur Ş Hatipoğlu,Monica P Goldklang,Jeanine M D'Armiento,Cheryl S Pirozzi,M Bradley Drummond,Igor Z Barjaktarevic,Wissam M Chatila,Megan S Devine,Charlie Strange,Robert A Sandhaus,Jacqueline M Parkin,Elizabeth Westfall,Vivian Y Lin,Robin Parks,Hui-Chien Kuo,Adzoa Ekue,Kelly L Moffitt,Jamie Inshaw,Inmaculada Aban,Mark T Dransfield,Robert A Stockley","doi":"10.1183/13993003.01019-2025","DOIUrl":"https://doi.org/10.1183/13993003.01019-2025","url":null,"abstract":"BACKGROUNDAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder that causes emphysema from lack of the AAT serpin anti-protease, leading to protease-anti-protease imbalance. Weekly intravenous AAT therapy (augmentation) is the only specific treatment available. Alvelestat is an oral inhibitor of neutrophil elastase (NE) in development as a novel approach to AATD therapy. Here, we tested the safety and mechanistic efficacy of alvelestat in severe AATD.METHODSWe conducted two complementary, double-blind, randomized, placebo-controlled, 12-week trials, incorporating two doses of alvelestat in AATD. ATALANTa investigated 120 mg twice daily, including a subset of participants also receiving augmentation; ASTRAEUS tested 120 mg and 240 mg twice a day without augmentation. Primary and secondary endpoints were the change in blood NE (the putative target) and its activity in AATD (Aα-Val360 and desmosine/isodesmosine) as well as safety and tolerability.RESULTSWe enrolled 161 participants (63 in ATALANTa and 98 in ASTRAEUS). Blood NE was significantly suppressed in both studies at both doses, with the greatest effect (>90% suppression) at the 240 mg BID dose. There was no effect of 120 mg on disease activity biomarkers, whilst the 240 mg dose demonstrated significant reduction Aα-Val360 and desmosine. The most common adverse event was headache, particularly at the 240 mg dose. No safety signals of concern were detected.CONCLUSIONSAlvelestat effectively suppressed NE and its activity at both doses, but only the 240 mg twice daily dose demonstrated relevant efficacy compared to placebo on disease activity biomarkers with a favourable safety profile. These findings support progression of the 240 mg twice daily dose into a clinical endpoint study.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"56 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083430","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":"Reduction of systemic inflammation by elexacaftor/tezacaftor/ivacaftor correlates with lung function improvement in cystic fibrosis.","authors":"Olga Halle,Simon Y Graeber,Julia Kontsendorn,Claudia Kessemeier,Jan-Niklas Falke,Jannik Schwabe,Katharina Schütz,Sophia T Pallenberg,Rebecca Dalferth,Ruth Grychtol,Felix C Ringshausen,Mirjam Stahl,Stephanie Thee,Jobst F Roehmel,Zulfiya Syunyaeva,Julia Duerr,Jaehi Chung,Stephanie Hirtz,Tatjana Uselmann,Iris Kühbandner,Claudia Rückes-Nilges,Azadeh Bagheri-Pothoff,Sandra Barth,Bianca Schaub,Folke Brinkmann,Stefanie Weber,Silke V Koningsbruggen-Rietschel,Mustafa Abdo,Markus Weckmann,Stefanie Widder,Gesine Hansen,Burkhard Tümmler,Olaf Sommerburg,Lutz Naehrlich,Marcus A Mall,Anna-Maria Dittrich","doi":"10.1183/13993003.00150-2025","DOIUrl":"https://doi.org/10.1183/13993003.00150-2025","url":null,"abstract":"BACKGROUNDTriple CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) rapidly improves airway and systemic inflammation in people with cystic fibrosis (CF). However, longitudinal effects on systemic inflammation and their relationship to lung function remain unknown.METHODSIn this prospective, observational, multicenter study, we analyzed peripheral blood neutrophil counts, C-reactive protein (CRP) and six pro-inflammatory serum cytokines in a cohort of 198 people with CF aged 6 years and older at baseline (BL) and follow-up visits 3, 12, and 24 months after initiation of ETI, compared to 74 age-matched healthy control participants (HCs).RESULTSNeutrophil counts and CRP, G-CSF, IL-1β, IL-6, and IL-8 were reduced to 71%, 40%, 41%, 63%, 46%, and 81% of median BL values after 3 months of therapy already (all p<0.05), whereas MCP-1 reached 82% of BL levels at 12 months only (p<0.05). Change from BL to 3 months correlated with improvements in percent predicted forced expiratory volume (ppFEV1) for all systemic inflammation parameters except IL-8 (Spearman's r: -0.17 to -0.42, p<0.05). All cytokines reached HC levels at or before 24 months. Decreased inflammation levels were sustained until 24 months for all parameters (p<0.05) except IL-6.CONCLUSIONSOur results demonstrate that ETI exerts rapid and sustained effects on systemic inflammation associated with lung function improvements in children, adolescents and adults with CF in a real-world, post-approval setting. However, our data also show that individual markers of systemic inflammation remain at levels above those of HCs, particularly in certain sub-groups, suggesting persistence or resurgence of residual systemic inflammation.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"37 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083343","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":"Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease.","authors":"Kinan El Husseini,Joyce S Lee,Pierre-Antoine Juge,Esther Ebstein,Sébastien Ottaviani,Raphaël Borie,Catherine Bancal,Marie-Pierre Debray,Caroline Kannengiesser,Ibrahima Ba,Sylvain Marchand-Adam,Christophe Richez,Hilario Nunes,Jerome Avouac,René-Marc Flipo,Lidwine Wemeau,Marie-Christophe Boissier,Thierry Schaeverbeke,Nathalie Saidenberg Kermanac'h,Leticia Kawano-Dourado,Vincent Cottin,Paul J Wolters,Benjamin Granger,Philippe Dieudé,Bruno Crestani","doi":"10.1183/13993003.00587-2025","DOIUrl":"https://doi.org/10.1183/13993003.00587-2025","url":null,"abstract":"BACKGROUNDShorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD.METHODSPatients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL<10th percentile. Lung disease progression was defined as death, lung transplant or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5%predicted, transfer capacity (TLCO) ≥10%predicted).RESULTSAmong 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82% versus 93%predicted) and TLCO (49% versus 63%predicted) at enrolment, and greater 12-months decline in FVC and DLCO in mixed effects models (-7.7%pred. 95%CI[-11.6,-3.8] p<0.001, -4.5%pred. [-7.2, -1.8] p=0.001, respectively), although transplant-free survival was similar over a median follow-up of 3.6 years (IQR[1.8,7.0]). Lung disease progression was observed within 12 months of enrolment in 33 patients (33%), more frequently in patients with short LTL (47% versus 22%, p univariate=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 95%CI[0.94,1.00] p=0.031 and 2.80 [0.99,8.29] p=0.056, respectively).CONCLUSIONSShort LTL is associated with baseline severity and 12-month progression in RA-ILD.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"2 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083337","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":"De novo SRRM2 variants in neuroendocrine cell hyperplasia of infancy and persistent tachypnea of infancy.","authors":"Camille Louvrier,Yohan Soreze,Julie Mesinele,Alix de Becdelièvre,Tifenn Desroziers,Valérie Nau,Florence Dastot-Le Moal,Romain Levergeois,Marie Legendre,Irina Giurgea,Marina Konyukh,Rola Abou Taam,Arnaud Becourt,Laure Cosson,Isabelle Gibertini,Raphaël Borie,Diana Rodriguez,Corinne Troadec,Aurore Coulomb L'Herminé,Jean-Christophe Dubus,Nadia Nathan","doi":"10.1183/13993003.00777-2025","DOIUrl":"https://doi.org/10.1183/13993003.00777-2025","url":null,"abstract":"BACKGROUNDNeuroendocrine cell hyperplasia of infancy (NEHI), also called persistent tachypnea of infancy (PTI), is a major cause of childhood interstitial lung disease. This rare lung disease is responsible for respiratory insufficiency in the first years of life. Non-pulmonary symptoms have also been reported, including failure to thrive and developmental delay. The pathophysiology of NEHI/PTI remains unclear. To identify candidate genes of NEHI/PTI, we performed whole genome and whole exome sequencing in a large cohort of deeply phenotyped patients.METHODSTrio whole genomes sequencing were performed (n=21) to identify a candidate gene. Following identification of a candidate gene, whole exomes sequencing wereas performed to screen this gene in the remaining NEHI/PTI patients (n=50).RESULTSFour de novo loss-of-function (LoF) variants of SRRM2 were identified in 4 out of 71 NEHI/PTI patients with typical pulmonary presentation. Serine/arginine repetitive matrix protein 2 (SRRM2) is involved in mRNA splicing, and LoF SRRM2 variants have recently been reported in patients with neurodevelopmental delay (NDD). All four NEHI/PTI patients also had mild NDD. The prevalence of SRRM2 LoF variants in our cohort (5.6%;95% CI: 1.6% to 13.8%) is 20 to 100 times higher than in reported patients with NDD without lung disease, therefore the phenotypic spectrum of SRRM2-associated disease should be extended to NEHI/PTI.CONCLUSIONThis study identifies SRRM2-related disorder as a monogenic cause of NEHI/PTI. These results suggest that NEHI/PTI patients should be evaluated by a paediatric neurologist and that SRRM2 sequencing should be included in every NEHI/PTI work-up.","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":"114 1","pages":""},"PeriodicalIF":24.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083338","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":"Multi-omic spatial profiling reveals the unique SARS-CoV-2 lung microenvironment and collagen VI as a predictive biomarker in severe COVID-19.","authors":"Éanna Fennell, Graham S Taylor, Ciara I Leahy, Aisling M Ross, Gary Reynolds, Tracey Perry, Esther Youd, Jacob Skidmore, Radwan Ramzi Radwan Darwish, Kelly J Hunter, Benjamin E Willcox, Philip Jermann, Chowdhury Arif Jahangir, Arman Rahman, William M Gallagher, Nadezhda Nikulina, Bassem Ben Cheikh, Oliver Braubach, Aaron T Mayer, Lawrence S Young, Dimitris Grammatopoulos, Sian Faustini, Alex Richter, Alexander C Dowell, Tonny Venith, Onn S Thein, Dhruv Parekh, Kylie B R Belchamber, David R Thickett, Aaron Scott, Richard Attanoos, Lucia Mundo, Stefano Lazzi, Lorenzo Leoncini, Gareth Leopold, Neil Steven, Jannie Marie Bülow Sand, Morten A Karsdal, Diana Julie Leeming, Stefan Dojcinov, Aedin Culhane, Paul G Murray, Matthew R Pugh","doi":"10.1183/13993003.01699-2023","DOIUrl":"10.1183/13993003.01699-2023","url":null,"abstract":"<p><strong>Background: </strong>While coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, few studies have characterised the immune response to COVID-19 in lung tissue. We sought to understand the pathogenic role of microenvironmental interactions and the extracellular matrix in post-mortem COVID-19 lung using an integrative multi-omic approach.</p><p><strong>Methods: </strong>Post-mortem formalin-fixed paraffin-embedded lung tissue from fatal COVID-19 and nonrespiratory death control lung underwent multi-omic evaluation by Quantseq Bulk RNA sequencing, Nanostring GeoMx spatial transcriptomics, RNAscope, multiplex immunofluorescence and immunohistochemistry, to evaluate virus distribution, immune composition and the extracellular matrix. Markers of extracellular synthesis and breakdown were measured in the serum of 215 patients with COVID-19 and 54 healthy volunteer controls using ELISA.</p><p><strong>Results: </strong>We found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was restricted to the pneumocytes and macrophages of early-stage disease. Spatial analyses revealed an immunosuppressive virus microenvironment, enriched for PDL1⁺IDO1⁺ macrophages and depleted of T-cells. Oligoclonal T-cells in COVID-19 lung showed no enrichment of SARS-CoV-2 specific T-cell receptors. Collagen VI was upregulated and contributed to alveolar wall thickening and impaired gas exchange in COVID-19 lung. Serum from COVID-19 patients showed increased levels of PRO-C6, a marker of collagen VI synthesis, predicted mortality in hospitalised patients.</p><p><strong>Conclusions: </strong>Our data refine the current model of respiratory COVID-19 with regard to virus distribution, immune niches and the role of the noncellular microenvironment in pathogenesis and risk stratification in COVID-19. We show that collagen deposition is an early event in the course of the disease.</p>","PeriodicalId":12265,"journal":{"name":"European Respiratory Journal","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233659","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}