American journal of respiratory and critical care medicine
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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.
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Am. J. Respir. Crit. Care Med. · Jun 2024
Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.
Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. ⋯ Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.
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Am. J. Respir. Crit. Care Med. · Jun 2024
Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor.
The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood. ⋯ IL-13 drives features of airway remodeling in severe asthma which are partially reversed by inhibiting IL-4Rα receptor in vitro.
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Am. J. Respir. Crit. Care Med. · Jun 2024
Single-Cell Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. ⋯ These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients 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 idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
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Am. J. Respir. Crit. Care Med. · Jun 2024
Airborne Nanoparticle Concentrations Are Associated with Increased Mortality Risk in Canada's Two Largest Cities.
Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated. ⋯ As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.