American journal of respiratory and critical care medicine最新文献

{"title":"Sex-related transcriptomic differences in idiopathic pulmonary fibrosis.","authors":"Aravind A Menon, Matthew Moll, Janelle V Pugashetti, Angela L Linderholm, Gabrielle Y Liu, Rachana Krishna, Shwu-Fan Ma, Imre Noth, Gary M Hunninghake, Carol Feghali-Bostwick, Auyon J Ghosh","doi":"10.1093/ajrccm/aamag080","DOIUrl":"10.1093/ajrccm/aamag080","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2510-2513"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282078","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":"Meaningful thresholds for change in quantitative computed tomography-derived fibrosis extent in idiopathic pulmonary fibrosis.","authors":"Dong Yeong Kim, Min-Ju Kim, Yu Jin Oh, Hye Jeon Hwang, Eun Jin Chae, Sang Min Lee, Sohee Park, Jang Ho Lee, Joon Beom Seo, Ho Yun Lee, Ho Cheol Kim, Jooae Choe","doi":"10.1093/ajrccm/aamag245","DOIUrl":"10.1093/ajrccm/aamag245","url":null,"abstract":"<p><strong>Rationale: </strong>Validated thresholds for clinically meaningful change in quantitative computed tomography (QCT) for fibrosis extent across algorithms remain unclear in idiopathic pulmonary fibrosis (IPF).</p><p><strong>Objectives: </strong>To evaluate minimal clinically important difference (MCID) for 1-year change in QCT metrics in IPF using different algorithms than previously reported and to identify prognostically meaningful thresholds for effective risk stratification.</p><p><strong>Methods: </strong>This multicenter retrospective study included IPF patients with baseline and 1-year follow-up CT. Minimal clinically important differences for change in fibrosis score (ΔFS) derived from fully automated CT quantification were estimated using an anchor-based approach with 1-year changes in FVC and diffusing capacity for carbon monoxide (DLco), and a prognostic threshold was estimated using maximally selected log-rank statistics. Prognostic significance of ΔFS was evaluated in discovery and validation cohorts.</p><p><strong>Results: </strong>The discovery cohort included 524 patients (mean age = 66.8 years; 79% men), and the external validation cohort included 224 patients (mean age = 69.6 years; 83% men). Anchor-based MCIDs were 2.72% for FVC and 4.52% for DLco, with a prognostic threshold of 4.05%. In the discovery cohort, 1-year ΔFS were independently associated with transplant-free survival (TFS), with greater risk when ΔFS exceeded MCID or prognostic thresholds (all, P < .001). In the validation cohort, ΔFS remained associated with TFS (adjusted hazard ratio [aHR] = 1.11; 95% CI, 1.04-1.18), and all prespecified ΔFS thresholds were prognostic for overall TFS, with the prognostic threshold of ΔFS ≥ 4.05% showing the most consistent associations with overall (aHR = 2.78; 95% CI, 1.36-5.68) and 3-year TFS (aHR = 2.88; 95% CI, 1.11-7.48).</p><p><strong>Conclusion: </strong>One-year change in FS and its thresholds were significantly associated with TFS, supporting annual CT follow-up with predefined QCT thresholds for monitoring and risk stratification in IPF.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2467-2481"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013134","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":"Reply to Schiller and to Schwartz et al.","authors":"Adam W Gaffney, Steffie Woolhandler, David Himmelstein, Philip J Landrigan","doi":"10.1093/ajrccm/aamag394","DOIUrl":"10.1093/ajrccm/aamag394","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2675-2676"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590292","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":"Correction to: Study Design Consideration in Inhaled Corticosteroid Dose and Adverse Events.","authors":"","doi":"10.1093/ajrccm/aamag304","DOIUrl":"10.1093/ajrccm/aamag304","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2693"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787223","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":"Opportunities for human lung tissue-based studies in fibrotic interstitial lung disease research.","authors":"Jeffrey M Sturek, John S Kim, Anna Podolanczuk, Riley T Hannan, Andrew H Limper, Lida P Hariri, Luca Richeldi, Ivan O Rosas, Gisli Jenkins, Fengming Luo, Sara Tomassetti, Jesse Roman, Patricia J Sime, Victor J Thannickal, Jonathan A Kropski, Naftali Kaminski, Fernando J Martinez, Imre Noth","doi":"10.1093/ajrccm/aamag346","DOIUrl":"10.1093/ajrccm/aamag346","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2338-2347"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359097","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":"ADAMTS14 is a novel modulator of fibroblast mechanoactivation in pulmonary fibrosis.","authors":"Ingo Ganzleben, Alok Jaiswal, Yang Yang, Daniela M Santos, Alyce Segal, Maxwell C McCabe, Eva M Medina, Gary Reynolds, Jing Zhang, Seok-Hyun Yun, Tommy Krug, David A Weitz, Desmond Chow Ming Chia, Bianca Ortiz Diaz, Lorena Pantano, Shannan Ho Sui, Rachel S Knipe, Patricia Brazee, Gina Pronzati, Katharine Black, Lida P Hariri, Cedrickx Godbout, Corinna Maier, Lukas M Altenburger, Tristan Kooistra, Thorsten R Mempel, Peter Seither, Franziska Herrmann, Ramnik J Xavier, Benjamin D Medoff","doi":"10.1093/ajrccm/aamag396","DOIUrl":"10.1093/ajrccm/aamag396","url":null,"abstract":"<p><strong>Rationale: </strong>Yes-associated protein (YAP)-mediated fibroblast mechanoactivation is an important driver of fibrosis in idiopathic pulmonary fibrosis (IPF).</p><p><strong>Objectives: </strong>To characterize the role of ADAM with thrombospondin motif 14 (ADAMTS14) in YAP-mediated fibroblast mechanoactivation and pulmonary fibrosis.</p><p><strong>Methods: </strong>We disrupted ADAMTS14 expression in primary human lung fibroblasts (HLFs) and demonstrated its role in YAP nuclear translocation and fibroblast activation. We confirmed the in vivo relevance of ADAMTS14 in an IPF patient cohort using transcriptomic studies. ADAMTS14-deficient fibroblasts were further characterized in mechanistic studies combining advanced microscopy, unbiased proteomics, and co-immunoprecipitation with functional mechanobiology assays to delineate substrate-matrix interactions.</p><p><strong>Measurements and main results: </strong>An unbiased siRNA screen identified ADAMTS14 as a regulator of YAP-mediated fibroblast activation and profibrotic activity. Transcriptomic analyses of patient samples with fibrotic lung disease identified an ADAMTS14-expressing fibroblast population characterized by excessive collagen matrix synthesis and located within fibroblastic foci of IPF patients. Disruption of ADAMTS14 expression in IPF patient-derived HLFs reduced profibrotic gene expression and attenuated the response to TGFβ. Mechanistically, we identified collagen V as a novel functionally relevant ADAMTS14 substrate essential for matrix stability. ADAMTS14-deficient fibroblasts produced an unstable extracellular matrix, leading to disorganized focal adhesions, impaired force transmission, and reduced focal adhesion-FAK-AKT signaling.</p><p><strong>Conclusions: </strong>We identify a novel ADAMTS14-collagen V-focal adhesion axis as a potential driver of fibroblast activation in IPF, linking extracellular proteolytic matrix remodeling to focal adhesion dynamics and YAP-mediated mechanoactivation. This feed-forward circuit provides a new mechanistic framework for pulmonary fibrosis and identifies potential novel therapeutic targets.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2386-2408"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597647","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":"From mechanisms to clinical practice: introduction to an AJRCCM special section on interstitial lung disease.","authors":"Anna J Podolanczuk, Wonder P Drake, Toby M Maher, Fernando J Martinez, Justin M Oldham, Patricia J Sime, Fengming Luo","doi":"10.1093/ajrccm/aamag433","DOIUrl":"10.1093/ajrccm/aamag433","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"2288-2289"},"PeriodicalIF":21.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787135","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":"Amikacin Liposome Inhalation Suspension in Newly Diagnosed\u0000 Mycobacterium avium\u0000 Complex Lung Disease: A Phase 3b, Double-blind, Randomized Clinical Trial (ENCORE)","authors":"Charles L Daley,Kozo Morimoto,Rachel Thomson,Eva Van Braeckel,Naoki Hasegawa,David E Griffith,Patrick A Flume,James D Chalmers,Kevin L Winthrop,Michael R Loebinger,Daniel Serrano,Jakko van Ingen,Dayton W Yuen,Mariam Hassan,Pan Wu,Marie-Laure Nevoret,Kevin Mange,Anne E O’Donnell,ENCORE Study Group","doi":"10.1093/ajrccm/aamag530","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag530","url":null,"abstract":"Abstract Rationale Current recommended front-line multidrug therapy (MDT) for Mycobacterium avium complex lung disease (MACLD) produces suboptimal outcomes. Amikacin liposome inhalation suspension (ALIS) with MDT is approved for refractory MACLD; however, clinical trial evidence in newly diagnosed MACLD is lacking. Objectives To evaluate efficacy and safety of ALIS with MDT in the phase 3b, randomized, double-blind, placebo-controlled superiority trial in adults newly diagnosed with MACLD who have not initiated antibiotics (ENCORE NCT04677569). Methods Patients (N = 425) were randomized 1:1 to receive ALIS 590 mg (n = 213) or placebo (n = 212) plus azithromycin 250 mg and ethambutol 15 mg/kg once daily for 12 months. Primary endpoint was change from baseline to month 13 in Respiratory Symptom Score (RSS). Pre-specified secondary endpoints included culture conversion (CC) at clinically important timepoints, durable culture conversion (DCC), and safety. Results Median age was 68.0 years, 62.8% were White, and 79.3% were female. Significantly greater improvements in RSS were observed in the ALIS versus comparator arm at 1 month post-treatment (month 13; LS mean change: 17.77 vs 14.66 points; treatment difference 3.11 points; P=0.0299), with improvements sustained at 3 months post-treatment (month 15; treatment arm difference 4.80 points; nominal P=0.0015). Significantly greater proportions of patients achieved CC by month 13 and DCC at month 15 in the ALIS arm versus comparator arm (82.4% vs 55.6% and 76.2% vs 47.6%, respectively; both P&amp;lt;0.0001). No new safety signals were observed. Conclusions ALIS with MDT was superior to the comparator arm for improving respiratory symptoms and CC in patients newly diagnosed with MACLD.","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"24 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089210","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":"Pulse versus Nonpulse Corticosteroid Therapy in Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Multicenter, Randomized Clinical Trial (SAFER).","authors":"Hyesoo Kim, Hye Jin Jang, Song Yee Kim, A La Woo, Eun Young Kim, Se Hyun Kwak, Eun Hye Lee, Ji Soo Choi, Min Kwang Byun, Chi Young Kim, Iseul Yu, Chang Youl Lee, Chang Hoon Han, Seon Cheol Park, Jae Ho Chung, Ji Eun Park, Ji Won Park, Sang-Ha Kim, Ganesh Raghu, Moo Suk Park","doi":"10.1093/ajrccm/aamag529","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag529","url":null,"abstract":"<p><strong>Rationale: </strong>Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high short-term mortality, yet guidelines weakly recommend corticosteroids without defining dose or duration. Pulse-dose methylprednisolone is widely used despite minimal evidence.</p><p><strong>Objectives: </strong>To test the superiority of a pulse-dose corticosteroid regimen over a nonpulse regimen with respect to short-term survival in AE-IPF.</p><p><strong>Methods: </strong>In this randomised, open-label, multicenter trial at eight South Korean university hospitals, adults with AE-IPF were assigned (1:1) to receive either intravenous pulse methylprednisolone (10 mg/kg for 3 days) or nonpulse regimen (1 mg/kg for 7 days), followed by protocolised tapering and maintenance low-dose prednisolone. Primary outcomes were all-cause mortality at 28 and 90 days. Secondary outcomes included intensive care unit admission, use of mechanical ventilation or extracorporeal membrane oxygenation, death or lung transplantation at 28 and 90 days, and adverse events. The trial was registered at ClinicalTrials.gov, NCT04996303.</p><p><strong>Measurements and main results: </strong>From July 2021 to April 2024, 100 patients were randomised (pulse n = 51; nonpulse n = 49). The pulse regimen did not demonstrate lower 28-day mortality than the nonpulse regimen (10.0% vs. 14.6%; risk difference, -4.6 percentage points; 95% CI, -18.8 to 9.1; P = 0.549) or lower 90-day mortality (24.5% vs. 29.8%; risk difference, -5.3 percentage points; 95% CI, -23.1 to 12.6; P = 0.648). Treating transplantation as a competing event, Fine-Gray analysis did not demonstrate a difference in 90-day mortality. Secondary outcomes were not demonstrably different between groups.</p><p><strong>Conclusions: </strong>Among adults with AE-IPF, pulse-dose methylprednisolone did not demonstrate improved 28- or 90-day survival compared with a nonpulse corticosteroid regimen.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079372","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":"Trends in Long-Term Oxygen Therapy Use and Modality Among Medicare Beneficiaries with COPD, ILD, and PH.","authors":"Darshali A Vyas, Sydney B Montesi, Josanna Rodriguez-Lopez, ZhaoNian Zheng, Jennifer P Stevens, Rishi K Wadhera","doi":"10.1093/ajrccm/aamag508","DOIUrl":"https://doi.org/10.1093/ajrccm/aamag508","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079467","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}