American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2024
Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.
Rationale: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. ⋯ Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of nontherapeutic cells and associated with decreased lung retention. Conclusions: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Hospitalization Rates in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Registry.
Rationale: Little is known about hospitalization in other types of interstitial lung disease (ILD) besides idiopathic pulmonary fibrosis (IPF). Objectives: To determine the frequency of hospitalizations in various types of ILD and elucidate the association of hospitalization with outcomes. Methods: An analysis of the Pulmonary Fibrosis Foundation Patient Registry data was performed. ⋯ Conclusions: Rates of hospitalization are similar across ILD subtypes. The risk of death or transplant after posthospitalization is lower in patients with CTD-ILD and non-IPF IIP, compared with patients with IPF. In a mixed population of participants with ILD, all-cause hospitalizations were not associated with decreased transplant-free survival; however respiratory-related hospitalizations were.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Pulmonary Ionocytes Regulate Airway Surface Liquid pH in Primary Human Bronchial Epithelial Cells.
Rationale: Pulmonary ionocytes are a newly discovered airway epithelial cell type proposed to be a major contributor to cystic fibrosis (CF) lung disease based on observations they express the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel at a higher level than any other cell type in the airway epithelia. Moreover, genetically manipulated experimental models that lack ionocytes develop NaCl transport abnormalities and airway surface liquid (ASL) dehydration consistent with CF. However, no direct evidence indicates ionocytes engage in NaCl transport or contribute to ASL formation, questioning the relevance of ionocytes to CF lung disease. ⋯ Conclusions: We conclude that ionocytes do not contribute to ASL formation but regulate ASL pH. Club cells secrete the bulk of airway fluid. In CF, abnormal ionocyte and club cell function results in acidic and dehydrated ASL, causing reduced antimicrobial properties and mucociliary clearance.
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Am. J. Respir. Crit. Care Med. · Sep 2024
Epigenome-Wide Association Studies of COPD and Lung Function: A Systematic Review.
Rationale: Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. Objectives: To systematically review the evidence form epigenome-wide association studies related to COPD and lung function. ⋯ A few genes (n = 123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research. Systematic Review [protocol] registered with Open Science Framework (OSF).