American journal of respiratory and critical care medicine最新文献

{"title":"Lung Cancer and the Environment.","authors":"Eric Garshick","doi":"10.1164/rccm.202504-0966ED","DOIUrl":"10.1164/rccm.202504-0966ED","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1120-1122"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172438","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 Hsiao and Chen: Refining the Concept of Disease Stability in Chronic Obstructive Pulmonary Disease: Bridging Complexity and Clinical Practice.","authors":"Dave Singh","doi":"10.1164/rccm.202501-0290LE","DOIUrl":"10.1164/rccm.202501-0290LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1308-1309"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735570","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":"We'll Look Back and Say, \"Why Didn't We Act Sooner on Engineered Stone?\"","authors":"David C Currow, Kate F Cole, Sanchia K Aranda, Malcolm R Sim","doi":"10.1164/rccm.202501-0282LE","DOIUrl":"10.1164/rccm.202501-0282LE","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1310"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771044","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":"Lipid Ratios for Diagnosis and Prognosis of Pulmonary Hypertension.","authors":"Natalie Bordag, Bence Miklos Nagy, Elmar Zügner, Helga Ludwig, Vasile Foris, Chandran Nagaraj, Valentina Biasin, Gabor Kovacs, Nikolaus Kneidinger, Ulrich Bodenhofer, Christoph Magnes, Bradley A Maron, Silvia Ulrich, Tobias J Lange, Thomas O Eichmann, Konrad Hoetzenecker, Thomas Pieber, Horst Olschewski, Andrea Olschewski","doi":"10.1164/rccm.202407-1345OC","DOIUrl":"10.1164/rccm.202407-1345OC","url":null,"abstract":"<p><p><b>Rationale:</b> Pulmonary hypertension (PH) poses a significant health threat. Current biomarkers for PH lack specificity and have poor prognostic capabilities. <b>Objectives:</b> To develop better biomarkers for PH that are useful for patient identification and management. <b>Methods:</b> An explorative analysis was conducted of a broad spectrum of metabolites in patients with PH, healthy control subjects, and diseased control subjects in training and validation cohorts, together with <i>in vitro</i> studies on human pulmonary arteries. <b>Measurements and Main Results:</b> High-resolution mass spectrometry was performed in 233 subjects coupled with machine learning analysis. Histologic and gene expression analysis was conducted, with a focus on lipid metabolism in human pulmonary arteries of idiopathic pulmonary arterial hypertension lungs and assessment of the acute effects of extrinsic fatty acids (FAs). We enrolled a training cohort of 74 patients with PH, 30 diseased control subjects without PH, and 65 healthy control subjects, as well as an independent validation cohort of 64 subjects. Among other metabolites, FAs were significantly increased. Machine learning showed a high diagnostic potential for PH. In addition, we developed fully explainable lipid ratios with exceptional diagnostic accuracy for PH (areas under the curve of 0.89 in the training cohort and 0.90 in the external validation cohort), outperforming machine learning results. These ratios were also prognostic and complemented established clinical markers and scores, significantly increasing their hazard ratios for mortality risk. Idiopathic pulmonary arterial hypertension lungs showed lipid accumulation and altered expression of lipid homeostasis-related genes. In human pulmonary artery smooth muscle and endothelial cells, FAs caused excessive proliferation and barrier dysfunction, respectively. <b>Conclusions:</b> Our metabolomics approach suggests that lipid alterations in PH provide diagnostic and prognostic information, complementing established markers. These alterations may reflect pathologic changes in the pulmonary arteries of patients with PH.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1264-1276"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957430","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":"Efficacy and Safety of Higher Doses of Levofloxacin for Multidrug-resistant Tuberculosis: A Randomized, Placebo-controlled Phase II Clinical Trial.","authors":"Patrick P J Phillips, Charles A Peloquin, Timothy R Sterling, Pawandeep Kaur, Andreas H Diacon, Eduardo Gotuzzo, Debra Benator, Robin M Warren, David Sikes, Leonid Lecca, Neel R Gandhi, Elizabeth M Streicher, Nancy Dianis, Kathleen Eisenach, Carole D Mitnick, C Robert Horsburgh","doi":"10.1164/rccm.202407-1354OC","DOIUrl":"10.1164/rccm.202407-1354OC","url":null,"abstract":"<p><p><b>Rationale:</b> Evaluation of optimal dosing has generally been inadequate during tuberculosis (TB) drug development. Fluoroquinolones are central to TB treatment. <b>Objective:</b> To determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. <b>Methods:</b> Opti-Q was an international, multicenter, randomized, placebo-controlled phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin for 24 weeks (168 doses) alongside a multidrug regimen: 11 mg/kg (750 mg), 14 mg/kg (750 mg/1,000 mg), 17 mg/kg (1,000 mg/1,250 mg) or 20 mg/kg (1,250 mg/1,500 mg). The primary efficacy outcome was time to sputum culture conversion, and the primary safety outcome was grade ≥3 adverse events (AEs). <b>Measurements and Main Results:</b> A total of 111 participants were randomized from three sites in South Africa and Peru. Eighty-three (75%) had cavities on chest X-ray, 55 (50%) had a smear grading of 3+, and the median body mass index was 20.4 kg/m². Median levofloxacin areas under the curve (AUCs)/minimum inhibitory concentrations were 573, 633, 918, and 1,343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank <i>P</i> = 0.282), by tertile of AUC/minimum inhibitory concentration (<i>P</i> = 0.350), or by dose received (<i>P</i> = 0.723); 69.3%, 74.8%, 70.6%, and 78.3% exhibited culture conversion after 8 weeks on solid media, respectively, across the treatment arms; along with 64.6%, 69.5%, 52.6%, and 69.6% on liquid culture. More participants experienced a grade 3-5 AE at higher doses (37.0% and 16.0% in the highest and lowest dose groups, respectively; <i>P</i> = 0.042, Cochran-Armitage test for trend) and higher tertiles of AUC (<i>P</i> = 0.011). <b>Conclusions:</b> As part of a multidrug regimen, doses of levofloxacin >1,000 mg/d resulted in greater exposures and increased frequency of AEs but did not result in faster time to sputum culture conversion. A dose of 1,000 mg/d can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT01918397).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1277-1287"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623105","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":"Unusual Presentation of Clear Cell Tumor of the Lung as Irregular Nodules with a Thin-walled Cavity.","authors":"Minli Lv, Qiang Gao, Jianquan Zhong","doi":"10.1164/rccm.202411-2124IM","DOIUrl":"10.1164/rccm.202411-2124IM","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"e11-e12"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771042","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":"Trial Analysis and Interpretation in Critical Care Using the Evidential (Likelihood) Approach: Rationale and Practical Considerations.","authors":"Fernando G Zampieri,Peter M B Cahusac,Israel S Maia,Nadir Yehya,Nuala J Meyer,Fan Li,Michael O Harhay","doi":"10.1164/rccm.202504-0809tr","DOIUrl":"https://doi.org/10.1164/rccm.202504-0809tr","url":null,"abstract":"Selecting the optimal methodological framework for evidence synthesis presents a fundamental challenge in contemporary clinical research. In critical care, where many interventions yield inconclusive results under traditional p-value-based analyses, complementary analytical approaches can enhance our understanding of trial data. While frequentist statistics remain predominant and Bayesian methods have recently experienced a resurgence of interest, the evidential (or likelihood) framework offers a methodological perspective that potentially bridges these two inferential paradigms. In this Concise Translational Review, we introduce readers to the evidential approach. To present the evidential approach as an analytical tool for critical care trials, we demonstrate its application using data from two mechanical ventilation trials (the Alveolar Recruitment Trial [ART, n=1,010] and the STrAtegy for coMmunIty acquired pNeumoniA trial [STAMINA, n=214]) and one trial evaluating balanced solutions (Balanced Solutions in Intensive Care Study - BaSICS, n=10,520). We focus on how concepts and terminology translate across paradigms, the framework's measures of effect (i.e., likelihood ratios, support values, and S intervals), proposals for its use in sequential analysis and trial monitoring, and how to report results from this framework in research articles. We propose that the evidential framework provides a clinically intuitive approach to trial interpretation by focusing on the relative evidence between competing hypotheses, thereby offering additional and complementary insights that align with clinical reasoning processes. To facilitate implementation by the scientific community, we have developed an interactive Shiny (open-source web-based) application (https://fzampier.shinyapps.io/Likelihood_Shiny/). This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":"19 1","pages":""},"PeriodicalIF":24.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533602","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":"Dual α_vβ₆ and α_vβ₁ Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial.","authors":"Sydney B Montesi, Gregory P Cosgrove, Scott M Turner, Iris Y Zhou, Nikos Efthimiou, Antonia Susnjar, Ciprian Catana, Caroline Fromson, Annie Clark, Martin Decaris, Chris N Barnes, Éric A Lefebvre, Peter Caravan","doi":"10.1164/rccm.202410-1934OC","DOIUrl":"10.1164/rccm.202410-1934OC","url":null,"abstract":"<p><p><b>Rationale:</b> Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of type I collagen. ⁶⁸Ga-CBP8, a type I collagen positron emission tomography probe, measures collagen accumulation and shows higher collagen deposition in patients with IPF. Bexotegrast (PLN-74809) is an oral, once-daily, dual-selective inhibitor of α_vβ₆ and α_vβ₁ integrins under late-stage evaluation for treatment of IPF. <b>Objectives:</b> To evaluate changes in type I collagen in the lungs of participants with IPF after treatment with bexotegrast. <b>Methods:</b> In this phase 2 (NCT05621252), single-center, double-blind, placebo-controlled study, adults with IPF received bexotegrast 160 mg or placebo for 12 weeks. The primary endpoint was the change in whole-lung standardized uptake value of ⁶⁸Ga-CBP8 positron emission tomography. Changes in lung dynamic contrast-enhanced magnetic resonance imaging parameters, FVC, cough severity, and biomarkers of collagen synthesis and progressive disease were also assessed. <b>Measurements and Main Results:</b> Of 10 participants, 7 received bexotegrast and 3 received placebo. At Week 12, the mean change from baseline in the top quartile of ⁶⁸Ga-CBP8 whole-lung standardized uptake value was -1.2% with bexotegrast versus 6.6% with placebo; the greatest mean changes were observed in subpleural lung regions in both groups (bexotegrast, -3.7%; placebo, 10.3%). Dynamic contrast-enhanced magnetic resonance imaging showed numerically increased peak enhancement and faster contrast washout rate in bexotegrast-treated participants, suggesting improvements in lung microvasculature and decreased extravascular extracellular volume. Bexotegrast treatment resulted in numerical improvements in FVC, cough severity, and biomarkers. <b>Conclusions:</b> The reduced uptake of ⁶⁸Ga-CBP8 in the lungs of participants with IPF indicates an antifibrotic effect of bexotegrast, suggesting the potential for favorable lung remodeling. Clinical trial registered with www.clinicaltrials.gov (NCT05621252).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1229-1240"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735549","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":"Approach to the Evaluation and Management of Interstitial Lung Abnormalities: An Official American Thoracic Society Clinical Statement.","authors":"Anna J Podolanczuk, Gary M Hunninghake, Kevin C Wilson, Yet H Khor, Fayez Kheir, Brandon Pang, Ayodeji Adegunsoye, Gretchen Cararie, Tamera J Corte, Jim Flanagan, Gunnar Gudmundsson, Lida P Hariri, Hiroto Hatabu, Stephen M Humphries, Bhavika Kaul, John S Kim, Melanie Konigshoff, Jonathan A Kropski, Joyce S Lee, Fengming Luo, David A Lynch, Fernando J Martinez, Sydney B Montesi, Yuben Moodley, Justin M Oldham, Sara Piciucchi, Rachel K Putman, Luca Richeldi, Ivan O Rosas, Margaret L Salisbury, Mary M Salvatore, Moises Selman, Joon Beom Seo, Jin Woo Song, Carey C Thomson, Marina Vivero, Louise V Wain, Marlies Wijsenbeek, David A Schwartz, Christopher J Ryerson","doi":"10.1164/rccm.202505-1054ST","DOIUrl":"10.1164/rccm.202505-1054ST","url":null,"abstract":"<p><p><b>Background:</b> There is growing interest in identifying early stages of interstitial lung disease (ILD) to improve patient outcomes. This document reviews updated evidence on interstitial lung abnormalities (ILAs); provides suggestions for screening, evaluation, and management; proposes criteria for distinguishing ILAs from ILD; and identifies research priorities. <b>Methods:</b> A committee of clinical and methodology experts met by video conference to define ILAs and ILD by consensus and voted on 11 prespecified questions after reviewing synthesized evidence from a systematic literature search. Agreement of ≥70% was required to approve each suggestion. <b>Results:</b> ILA is defined as nondependent bilateral parenchymal abnormalities on computed tomography, including ground-glass opacities or reticulations, lung distortion, traction bronchiectasis, and/or honeycombing involving ≥5% of a lung zone. The updated definition removes the prior exclusion of high-risk populations. ILD is distinguished from ILAs by symptoms (dyspnea/cough) attributable to an interstitial process, abnormal or declining lung function, fibrotic (honeycombing and/or reticulation with traction bronchiectasis involving ≥5% of total lung volume) or progressive imaging abnormalities, and/or specific fibrotic ILD patterns on imaging or pathology. Suggestions include ILA/ILD assessment on imaging acquired for lung cancer screening, screening adults with connective tissue disease and first-degree relatives of patients with familial pulmonary fibrosis, assessing baseline symptoms and pulmonary function among those with ILAs, and monitoring ILAs with chest computed tomography every 2-3 years. <b>Conclusions:</b> This document presents a comprehensive literature review of ILAs with updates to the Fleischner Society ILA definition, establishes a working ILD definition, and provides evidence-based suggestions for ILA evaluation and management.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1132-1155"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092548","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":"Airway Scaffolds for Emphysema-related Hyperinflation: Six-Month Results from the BREATHE Trial.","authors":"Anand Tana, Arschang Valipour, Alvin Ing, Daniel P Steinfort, Christopher M Orton, Karin Klooster, Theresa Klemm, Jonathan P Williamson, Jemma J Christie, Justin L Garner, T David Koster, Kelly Welz, Marlies van Dijk, Martin L Mayse, Pallav L Shah, Dirk-Jan Slebos","doi":"10.1164/rccm.202502-0378OC","DOIUrl":"10.1164/rccm.202502-0378OC","url":null,"abstract":"<p><p><b>Rationale:</b> Despite advancements in emphysema treatment, high morbidity and mortality rates highlight the need for innovative therapies. A novel self-expanding nitinol airway scaffold was designed to alleviate lung hyperinflation by connecting emphysematous parenchyma with central bronchi, releasing trapped air. <b>Objectives:</b> To assess the feasibility, safety, and initial outcomes of airway scaffolds in treating emphysema-related hyperinflation. <b>Methods:</b> We conducted a pooled analysis of two first-in-human studies (NCT05949645, NCT05854550) involving patients with heterogeneous or homogeneous emphysema treated bronchoscopically with up to three permanent airway scaffolds per lung. <b>Measurements and Main Results:</b> The primary outcome was safety, measured by procedure- and/or device-related serious adverse events over 6 months. Secondary outcomes were technical feasibility, pulmonary function, quality of life, symptoms, exercise capacity at 3 and 6 months, and airway patency assessment by high-resolution computed tomography. Sixty severe emphysema patients (33 female, 27 male; mean age, 66 ± 8 yr; mean residual volume percent predicted, 255 ± 47%) were included. Ninety-eight procedures were performed, and 328 airway scaffolds were successfully placed. A proportion of 21.7% of patients experienced at least one related serious adverse event within 6 months, including pneumonia (10.0%) and chronic obstructive pulmonary disease exacerbation (5.0%), but no pneumothoraxes occurred. Residual volume improved (decreased) from baseline by a mean [95% confidence interval] of 866 [626, 1,106] ml at 3 months and 753 [512, 994] ml at 6 months. Clinically meaningful improvements were further observed in spirometry, quality of life, symptoms, and exercise capacity. <b>Conclusions:</b> This study provides the first clinical evidence of the feasibility, safety, and initial outcomes after treatment with airway scaffolds in patients with emphysema-related hyperinflation.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"1175-1184"},"PeriodicalIF":19.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092475","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}