American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2024
Single-Cell Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Rationale: Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in FHP in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico. ⋯ These results are publicly available at http://ildimmunecellatlas.com. Conclusions: Single-cell transcriptomics of patients with FHP uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells-reflecting this disease's unique inflammatory T cell-driven nature-as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in IPF. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
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Am. J. Respir. Crit. Care Med. · Nov 2024
ReviewObesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches.
Although obesity-related asthma is associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and GLP-1 (glucagon-like-peptide 1) receptor agonists, have been associated with improved asthma outcomes, although GLP-1R agonist data in asthma are limited to individuals with comorbid obesity. ⋯ Potential therapeutic targets include adipose tissue eosinophils and the GLP-1-arginine-advanced glycation end products axis, although data in humans are still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of IFN-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, to facilitate effective treatment development for this unique asthma phenotype.
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Am. J. Respir. Crit. Care Med. · Nov 2024
Profiling Bacteria in the Lungs of Patients with Severe Influenza Versus COVID-19 with or without Aspergillosis.
Rationale: The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) has yet to be explored. Objectives: To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. Methods: We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission. ⋯ Conclusions: Aspergillosis is more frequently detected in the lungs of patients with severe influenza than bacterial pathogens. Detection of bacterial pathogens associates with worse outcome in patients with influenza, particularly in those with IAPA, but not in patients with COVID-19. The immunological dynamics of tripartite viral-fungal-bacterial interactions deserve further investigation.