American journal of respiratory and critical care medicine最新文献

{"title":"Targeted Lung Denervation in COPD: Threading the Needle of Safe Interventions to Help the Sickest.","authors":"Yukiko Kunitomo,Nirupama Putcha","doi":"10.1164/rccm.202507-1793ed","DOIUrl":"https://doi.org/10.1164/rccm.202507-1793ed","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"30 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235905","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":"p300-Dependent Modulation in Regulatory T Cells Plays a Crucial Role in Allergic Asthma.","authors":"Eun Gyul Kim,Mi Na Kim,Soo-Yeon Park,Chang Hyun Park,Joo Yeon Cho,Byung Chan Ko,Sung Woo Park,Kyung Won Kim,Ho-Geun Yoon,Myung Hyun Sohn","doi":"10.1164/rccm.202407-1410oc","DOIUrl":"https://doi.org/10.1164/rccm.202407-1410oc","url":null,"abstract":"RATIONALEAsthma is a chronic inflammatory airway disease, affected by epigenetic modifications. E1A binding protein p300 (p300) is a pivotal histone acetyltransferase that regulates the transcription of diverse genes.OBJECTIVESWe investigated the role of p300 in regulating immune responses during allergic asthma.METHODSAn allergen-induced asthma model was established in mice with systemic p300 deletion and regulatory T cell (Treg)-specific p300 deletion. Histone acetyltransferase activity and p300 expression were evaluated in asthma-induced mice and biopsy samples from patients with asthma. Next, immune responses of T helper 2 cells and Tregs were investigated. Additionally, chromatin immunoprecipitation- and RNA-sequencing were conducted using the sorted Tregs. Functional studies of guanylate binding protein 5 (GBP5) in Tregs were confirmed through in vitro inhibition and overexpression tests.MEASUREMENTS AND MAIN RESULTSHistone acetyltransferase activity and p300 levels were elevated in mice with asthma. p300 expression was also higher in patients with asthma than in control subjects. Mice with systemic p300 deletion had elevated type-2 immune responses and decreased Treg population and functions. Furthermore, p300 deletion reduced the suppression ability and differentiation potential of Tregs. Allergic inflammation was also exacerbated in mice with Treg-specific p300 deletion. Chromatin immunoprecipitation- and RNA-sequencing revealed GBP5 as a primary target gene of p300 in Tregs. GBP5 overexpression ameliorated the reduction in Treg proliferation caused by p300 depletion.CONCLUSIONSp300 plays a protective role in allergic asthma by enhancing Treg function, partly through GBP5-mediated regulation, thereby suppressing Th2-driven airway inflammation.","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"9 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235904","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":"Think Locally, Act Globally: Resolving the Peripheral Immune Milieu in Bacterial Pneumonia.","authors":"John Michael Sanchez,Hrishikesh S Kulkarni","doi":"10.1164/rccm.202508-1838ed","DOIUrl":"https://doi.org/10.1164/rccm.202508-1838ed","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"197 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235901","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 to Yang and Chu: Methodological Considerations in the Iloprost for Septic Shock Trial.","authors":"François Dépret,David Chen,Matthieu Legrand","doi":"10.1164/rccm.202508-1854le","DOIUrl":"https://doi.org/10.1164/rccm.202508-1854le","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"6 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235903","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 to Zeng: The SOOTHE Trial of Camlipixant in RCC: A Cautionary Note on Stratification and Relevance.","authors":"Jaclyn A Smith","doi":"10.1164/rccm.202507-1640le","DOIUrl":"https://doi.org/10.1164/rccm.202507-1640le","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"158 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235910","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":"Spontaneous Pneumothorax as First Presentation of Pulmonary Alveolar Microlithiasis.","authors":"Lü Wang,Biao Wang","doi":"10.1164/rccm.202412-2469im","DOIUrl":"https://doi.org/10.1164/rccm.202412-2469im","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"320 1","pages":"e18-e19"},"PeriodicalIF":24.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153511","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":"Heat Wave Risks for People with Lung Disease.","authors":"Bridget F Collins,Krishna M Sundar,Jane E Gross,W Graham Carlos,Shazia M Jamil","doi":"10.1164/rccm.v211i10p16","DOIUrl":"https://doi.org/10.1164/rccm.v211i10p16","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"23 1","pages":"P16-P17"},"PeriodicalIF":24.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153510","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":"Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children ≥6 Years with Cystic Fibrosis and at Least One <i>F508del</i> Allele: A 192-Week, Phase 3, Open-Label Extension Study.","authors":"Claire Wainwright, Susanna A McColley, Paul McNally, Michael Powers, Felix Ratjen, Jonathan H Rayment, George Retsch-Bogart, Erica Roesch, Bonnie Ramsey, Edward F McKone, Elizabeth Tullis, Marcus A Mall, Jennifer L Taylor-Cousar, David Waltz, Neil Ahluwalia, Chenghao Chu, Christina V Scirica, Jane C Davies","doi":"10.1164/rccm.202502-0512OC","DOIUrl":"10.1164/rccm.202502-0512OC","url":null,"abstract":"<p><p><b>Rationale:</b> Elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) was shown to be safe and efficacious in children 6 through 11 years of age with cystic fibrosis (CF) and at least one <i>F508del</i> allele in a 24-week phase 3 study. Children completing this study could enroll into a 192-week extension study. <b>Objectives:</b> To evaluate the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years of age. <b>Methods:</b> In this two-part (part A [96 wk] and part B [96 wk]) phase 3 extension study, children <12 years of age weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, and children weighing ≥30 kg or aged ≥12 years received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours. <b>Measurements and Main Results:</b> Sixty-four children (<i>F508del</i>/minimal function [<i>n</i> = 36] and <i>F508del</i>/<i>F508del</i> [<i>n</i> = 28]) received at least one dose of ELX/TEZ/IVA. Mean exposure was 156.2 weeks, and 60.9% of children (<i>n</i> = 39) completed treatment in both parts of this 192-week study. The primary endpoint was safety. All children had adverse events, which for most were mild (31.3%) or moderate (64.1%) and generally consistent with common manifestations of CF. Two children (3.1%) had nonserious adverse events that led to treatment discontinuation (increased alanine aminotransferase [<i>n</i> = 1] and aggression [<i>n</i> = 1]). Secondary endpoints focused on efficacy. From parent study baseline, improvements were seen in percentage predicted FEV₁ (9.6 percentage points [95% confidence interval (CI), 5.4 to 13.7 percentage points]), sweat chloride concentration (-57.9 mmol/L [95% CI, -63.3 to -52.5 mmol/L]), Cystic Fibrosis Questionnaire-Revised respiratory domain score (10.0 points [95% CI, 6.9 to 13.0 points]), lung clearance index at a 2.5% stopping point (-2.33 [95% CI, -2.87 to -1.79]), and body mass index <i>z</i>-score (0.39 [95% CI, 0.19 to 0.59]) at Week 192. The rate of pulmonary exacerbations per year was 0.05. The annualized rates of change in percentage predicted FEV₁ and lung clearance index at a 2.5% stopping point were -0.09 percentage points (95% CI, -1.01 to 0.84 percentage points) and -0.07 units (95% CI, -0.12 to -0.01 units), respectively. <b>Conclusions:</b> In this 4-year extension study in children ≥6 years of age, the longest clinical trial experience with a CFTR (cystic fibrosis transmembrane conductance regulator) modulator in this pediatric population, ELX/TEZ/IVA remained generally safe and well tolerated, with no new safety findings. Clinically meaningful improvements in lung function, CFTR function, and nutritional status reported in the parent study were maintained. These results confirm the long-term safety and efficacy of ELX/TEZ/IVA in children ≥6 years of age.Clinical trial registered with www.clinicaltrials.gov (NCT04183790).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1915-1925"},"PeriodicalIF":19.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198065","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":"Rapid On-Site Evaluation of Cryobiopsies in Interstitial Lung Disease Using Higher Harmonic Generation Microscopy.","authors":"Kirsten A Kalverda,Laura M G van Huizen,Jan von der Thüsen,Venerino Poletti,Teodora Radonic,Chris Dickhoff,Johannes M A Daniels,Peter I Bonta,Jouke T Annema,Marie Louise Groot","doi":"10.1164/rccm.202505-1225rl","DOIUrl":"https://doi.org/10.1164/rccm.202505-1225rl","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"73 1","pages":"1876-1879"},"PeriodicalIF":24.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153509","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":"Genetic Associations in Non-Europeans with Pulmonary Fibrosis: Analysis of the All of Us Cohort.","authors":"Jiheum Park, Stephanie Shue, David Zhang","doi":"10.1164/rccm.202506-1331RL","DOIUrl":"10.1164/rccm.202506-1331RL","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1882-1885"},"PeriodicalIF":19.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844021","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}