ArticleAmerican journal of respiratory and critical care medicine2026
Airway epithelial heterogeneity and mucus plugging in asthmatic bronchioles.
Article in American journal of respiratory and critical care medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Airway mucus plugs in asthma and chronic obstructive pulmonary disease: pathobiology, imaging, and implications for clinical trials.American journal of respiratory and critical care medicine · 2026Review
- TSLP impairs mucociliary transport by inhibiting JAK signaling in both central and peripheral airways.Pflugers Archiv : European journal of physiology · 2026Article
- Contemporary Concise Review 2025: Asthma.Respirology (Carlton, Vic.) · 2026Review
- Reprogramming Inflammatory Macrophages with Specialized Pro-Resolving Lipid Mediators: A Novel Immunotherapeutic Strategy for Asthma.Biomedicines · 2026Review
- When asthmatic distal airways lose their identity: a new mechanism of mucus plugs pathogenesis.American journal of respiratory and critical care medicine · 2026Article
- Identification of imaging-based pulmonary and extrapulmonary treatable traits in COPD: a review.Frontiers in medicine · 2026Review
- Research Progress on the Mechanisms of High Mucus Secretion in the Airway: A Scoping Review.International journal of chronic obstructive pulmonary disease · 2026Article
- Airway epithelial dysfunction in asthma pathogenesis: epigenetic mechanisms, inflammatory crosstalk, and therapeutic opportunities.Frontiers in allergy · 2026Review
Corrections and comments
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Authors and funding
33 authors.
Funding
Abstract
rationaleBronchiolar dysfunction is associated with asthma exacerbations and poor symptom control. However, the molecular pathophysiology of asthmatic bronchiolar disease is poorly defined.
objectivesTest the hypothesis that asthmatic bronchioles exhibit disturbances in epithelial biology that produce MUC5AC-dominated mucus plugs.
methodsPeripheral lung tissues from severe asthmatics, fatal asthmatics (FA), and controls were evaluated with histology, RNA in situ hybridization, and immunohistochemistry. Isolated bronchiolar and bronchial basal cell responses to IL13 were compared in culture. Spatial transcriptomics and multiplex immunophenotyping were performed on excised tissue sections. MEASUREMENTS AND MAIN
resultsIn excised tissues, severe and FA bronchiolar epithelia, depleted of distal airway secretory cells (DASCs) and enriched in MUC5AC goblet cells, circumscribed MUC5AC-dominated mucus plugs. In cultured bronchiolar basal cells, IL13 suppressed FOXA2 and DASC gene signatures and upregulated MUC5AC expression. Additional studies in severe and FA-excised tissues demonstrated that bronchiolar epithelia were populated by MUC5AC-expressing goblet cell niches heterogeneously distributed within single segments and, indeed, individual bronchioles. Spatial transcriptomics and immuno-proteomics of these MUC5AC-expressing bronchiolar niches identified increased goblet, suprabasal (SERPINB3), and basal cells, juxtaposed to a loss of DASC gene signatures. MUC5AC-high niche bronchiolar basal cells expressed reduced FOXA2 and elevated type-2 inflammatory (T2) gene signatures. Immune cell distributions surrounding asthmatic bronchioles differed from controls but did not correlate with MUC5AC-high niches.
conclusionsAsthmatic bronchioles exhibit a T2-driven proximalization associated with mucus plugging. MUC5AC-high niches were identified heterogeneously in bronchiolar epithelia independent of immune cell localizations, suggesting asthmatic bronchioles contain cellular niches which perpetuate T2-initiated epithelial remodeling.
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