American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jun 2024
Lung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations.
While many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort. ⋯ This study identified emphysema-related changes in gene expression and alternative splicing, cell-type specific dysregulated pathways, and instances of shared pathway dysregulation between blood and lung.
-
Am. J. Respir. Crit. Care Med. · Jun 2024
Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.
Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. ⋯ However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.
-
Am. J. Respir. Crit. Care Med. · Jun 2024
Editorial Comment LetterAlveolar Collapse as a Threat to Mechanically Ventilated Lungs.
-
Am. J. Respir. Crit. Care Med. · Jun 2024
Limiting Overdistention or Collapse when Mechanically Ventilating Injured Lungs: A Randomized Study in a Porcine Model.
Rationale: It is unknown whether preventing overdistention or collapse is more important when titrating positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). Objectives: To compare PEEP targeting minimal overdistention or minimal collapse or using a compromise between collapse and overdistention in a randomized trial and to assess the impact on respiratory mechanics, gas exchange, inflammation, and hemodynamics. Methods: In a porcine model of ARDS, lung collapse and overdistention were estimated using electrical impedance tomography during a decremental PEEP titration. ⋯ Inflammatory markers were not significantly different. Conclusions: PEEP to minimize overdistention resulted in high mortality in an animal model of ARDS. Minimizing collapse or choosing a compromise between collapse and overdistention may result in less lung injury, with potential benefits of the compromise approach.