American journal of respiratory and critical care medicine
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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.
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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
Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD.
Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics. Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. ⋯ Finally, using spatial transcriptomics, we characterized the small airway differences between C#3 and C#4, identifying an upregulation of T-/B-cell homing chemokines and bacterial response genes in C#3. Conclusions: A novel multilayer network analysis is able to identify clinically relevant COPD patient communities. Patients with similarly low FEV1 and emphysema can have molecularly distinct small airways and immune response patterns, indicating that different endotypes can lead to similar clinical presentation.