American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2024
Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis (NCFB).
Rationale: Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Objectives: Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. ⋯ Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, and IL-1β-producing macrophages in mucus plugs and downregulation of epithelial ciliogenesis genes. Conclusions: NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia.
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Am. J. Respir. Crit. Care Med. · Feb 2024
Prevalence, Diagnostic Utility and Associated Characteristics of Bronchodilator Responsiveness.
Rationale: The prevalence and diagnostic utility of bronchodilator responsiveness (BDR) in a real-life setting is unclear. Objective: To explore this uncertainty in patients aged ⩾12 years with physician-assigned diagnoses of asthma, asthma and chronic obstructive pulmonary disease (COPD), or COPD in NOVELTY, a prospective cohort study in primary and secondary care in 18 countries. Methods: The proportion of patients with a positive BDR test in each diagnostic category was calculated using 2005 (ΔFEV1 or ΔFVC ⩾12% and ⩾200 ml) and 2021 (ΔFEV1 or ΔFVC >10% predicted) European Respiratory Society/American Thoracic Society criteria. ⋯ In patients diagnosed with COPD, BDR (2021) was associated with lower lung function and higher symptom burden. Conclusions: BDR prevalence in patients with chronic airway diseases receiving treatment ranges from 18% to 30%, being modestly lower with the 2021 than with the 2005 European Respiratory Society/American Thoracic Society criteria, and it is associated with lower lung function and greater symptom burden. These observations question the validity of BDR as a key diagnostic tool for asthma managed in clinical practice or as a standard inclusion criterion for clinical trials of asthma and instead suggest that BDR be considered a treatable trait for chronic airway disease.
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Am. J. Respir. Crit. Care Med. · Feb 2024
Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation.
Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 μm nylon 6,6 (nylon) and 15 × 52 μm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. ⋯ Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.