American journal of respiratory and critical care medicine最新文献

{"title":"Human Sputum Microbiome Composition and Sputum Inflammatory Cell Profiles Are Altered with Controlled Wood Smoke Exposure as a Model for Wildfire Smoke.","authors":"Catalina Cobos-Uribe, Radhika Dhingra, Martha A Almond, Neil E Alexis, David B Peden, Jeffrey Roach, Meghan E Rebuli","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>Wood smoke exposure is increasing worldwide due to the rise in wildfire events. Various studies have associated exposure to wildfire-derived smoke with adverse respiratory conditions. However, the mechanism by which this occurs is unknown. Previous studies using wood smoke as a model of wildfire smoke have focused on the respiratory immune response and have reported increased neutrophil percentage and cytokine production in airway samples. The effect of wood smoke on the respiratory microbiome, however, has not been examined.</p><p><strong>Methods: </strong>Healthy volunteers (N=54) were subjected to controlled wood smoke exposure (500 µg/m3) for two hours, and induced sputum samples were collected and processed for microbiome analysis, immune mediators, and cell differentials at baseline, six- and 24-hours post-exposure. A negative binomial mixed model analysis examined associations between microbiome components and inflammatory cells in sputum.</p><p><strong>Main results: </strong>Following wood smoke exposure, while sputum microbiome diversity remained unchanged, the microbiome composition was altered, particularly the abundance of several low-abundance bacteria, including <i>Fretibacterium</i> and <i>Selenomonas</i>, indicating that this inhalational exposure can alter the composition of the sputum microbiome. Additionally, a significant decrease in macrophage cells was observed at 24 hours without a significant change in neutrophils. We further found small but significant associations between different taxa and macrophages (per mg of sputum), including a negative association with <i>Fretibacterium</i>.</p><p><strong>Conclusions: </strong>Together, these findings demonstrate that inhalational wood smoke exposure can modify several low-abundance bacteria within the respiratory microbiome and that these changes are associated with sputum inflammatory cell alterations, providing insights for future studies to focus on respiratory innate immune host-microbiome crosstalk in the context of environmental exposures.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075505","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":"Loss of Lung Function Led to Loss of Life During the COVID-19 Pandemic.","authors":"Rachel L Eddy, Don D Sin","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075506","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":"Chest Imaging with a Collagen-Binding Probe - A Human Hydroxyproline Assay?","authors":"Sarah L Khan, Daniel J Kass","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075504","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 Telacebec-shaped Puzzle Piece in the Treatment of Mycobacterial Diseases.","authors":"Bouke B C de Jong","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952336","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":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>Pulmonary hypertension (PH) poses a significant health threat. Current biomarkers for PH lack specificity and have poor prognostic capabilities.</p><p><strong>Objectives: </strong>To develop better biomarkers for PH that are useful for patient identification and management.</p><p><strong>Methods: </strong>Explorative analysis of a broad spectrum of metabolites in PH patients, healthy controls and disease controls in a training and a validation cohort and <i>in vitro</i> studies on human pulmonary arteries.</p><p><strong>Measurements: </strong>High resolution mass spectrometry in 233 subjects coupled with machine learning analysis. Histologic and gene expression analysis with focus on lipid metabolism in human pulmonary arteries (PA) of idiopathic pulmonary arterial hypertension lungs (IPAH) and assessment of the acute effects of extrinsic fatty acids (FAs).</p><p><strong>Results: </strong>We enrolled a training cohort of 74 PH patients, 30 disease controls without PH, and 65 healthy controls, and an independent validation cohort of 64 subjects. Among other metabolites, the FAs were significantly increased. Machine learning showed a high diagnostic potential for PH. Additionally, we developed fully explainable lipid ratios with exceptional diagnostic accuracy for PH (AUC 0.89 training cohort, 0.90 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. IPAH lungs showed lipid accumulation and altered expression of lipid homeostasis-related genes. In human PA smooth muscle and endothelial cells, FAs caused excessive proliferation and barrier dysfunction, respectively.</p><p><strong>Conclusion: </strong>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 PH patients.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-09","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":"Clustering Pulmonary Hypertension Patients Using the Plasma Proteome.","authors":"Athénaïs Boucly, Shanshan Song, Merve Keles, Dennis Wang, Luke S Howard, Marc Humbert, Olivier Sitbon, Allan Lawrie, A A Roger Thompson, Philipp Frank, Mika Kivimaki, Christopher J Rhodes, Martin R Wilkins","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with pulmonary hypertension are classified according to clinical criteria to inform treatment decisions. Knowledge of the molecular drivers of pulmonary hypertension might better inform treatment choice.</p><p><strong>Methods: </strong>Between 2013 and 2021, 470 patients with pulmonary hypertension, 136 disease controls and 59 healthy controls were enrolled as a discovery cohort. Plasma levels of 7288 proteins were assayed (SomaScan 7K platform). Proteins that distinguished pulmonary hypertension from both control groups were selected for unsupervised clustering (k-means clustering of UMAP dimensions). Clinical characteristics and outcomes were compared across clusters. Separate cohorts of serially sampled patients from pulmonary hypertension centers in the United Kingdom (n=229) and France (n=79) provided independent validation.</p><p><strong>Results: </strong>156 plasma proteins that distinguished pulmonary hypertension from disease and healthy controls formed 4 clusters with diverse 5-year survival rates: 78% (cluster 4), 62% (cluster 2), 44% (cluster 3), and 33% (cluster 1). The distinction and clinical relevance of the clusters were confirmed in validation cohorts by their association with survival. To further characterise the therapeutic relevance of the clusters we investigated 2 experimental drug targets: the Platelet-Derived Growth Factor (PDGF) pathway was up-regulated in cluster 3 compared to other clusters and the Transforming Growth Factor-β (TGF-β) pathway was up-regulated in cluster 1.</p><p><strong>Conclusion: </strong>Plasma proteomic profiling of patients with pulmonary hypertension distinguishes 4 clusters, independent of the clinical classification. These groups, based on differential plasma protein levels, could act as theragnostic biomarkers for new therapies targeting PDGF and TGF-β pathways. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957134","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 Domínguez de la Cruz <i>et al.</i>: Little Big Issues in Brain-Lung Crosstalk.","authors":"Dimitrios Georgopoulos","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952041","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":"Social Determinants of Health and Racial Disparities in Lung Function: Findings from NHANES 2007-2012.","authors":"Amin Adibi, Christopher Carlsten, Emily P Brigham, Don D Sin, Peter Loewen, Mohsen Sadatsafavi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Rationale: </strong>We hypothesized that the disproportionate impact of social determinants of health (SDoH) captured in survey data could help explain a larger proportion of racial gaps in lung function than previously reported.</p><p><strong>Methods: </strong>We defined a series of nested, increasingly healthy reference populations using data from NHANES 2007-2012. Starting with non-smokers without respiratory symptoms or diagnoses, we sequentially excluded those with confirmed occupational exposure to dust/fumes, physical inactivity, maternal or second-hand tobacco use, obesity, no home ownership, no insurance, lower education, and self-reported unhealthy diet. Across successive populations, we compared average age-, sex-, and height-adjusted differences in FEV1 and FVC between racial and ethnic minority groups and Non-Hispanic White participants for adults (≥20) and children (6-19).</p><p><strong>Results: </strong>In successively healthier reference populations, the proportion of represented participants declined for Non-Hispanic Black, Mexican American, and Other Hispanic, increased for non-Hispanic White, and remained stable for Non-Hispanic Asian participants. At baseline, adjusted FEV1 and FVC were similar for Mexican Americans and non-Hispanic White Americans, but lower for other racial and ethnic minority groups. After excluding individuals with unfavorable SDoH, racial disparities in FEV1 and FVC decreased for Non-Hispanic Black children (24.8% and 26.2%) and adults (26.3% and 19.4%), Other Hispanic children (15.2% and 19.3%) and adults (85.9% and 12.4%), and Non-Hispanic Asian children (6.6% and 12.5%), but increased for Non-Hispanic Asian adults (14.1% and 11.1%).</p><p><strong>Conclusions: </strong>Unfavorable SDoH disproportionately affected non-Hispanic Black, Mexican American, and Other Hispanic populations, and explained a higher proportion of racial disparities in lung function than previously reported.</p>","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958546","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":"Little Big Issues in Brain-Lung Crosstalk.","authors":"Ines Domínguez de la Cruz, Lluis Blanch, Guillermo M Albaiceta","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960071","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":"Letting Cooler Heads Prevail: The Necessity of Occupational Regulation of Heat and Smoke Exposure.","authors":"Maeve Georgia MacMurdo, Hasan Bayram, Emily Brigham, Daniel Croft, Gillian Goobie, Alison G Lee, Laura C Myers, Nicholas Nassikas, Jared Radbel","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7664,"journal":{"name":"American journal of respiratory and critical care medicine","volume":" ","pages":"None"},"PeriodicalIF":19.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970259","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}