Insights into the effects of inhaled drugs on airway epithelium with human airway basal cells

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RATIONALE: Inhaled drugs are the first-line treatment for asthma, yet their effects on airway epithelial remodeling remain unclear. OBJECTIVES: We investigated how inhaled drugs affect epithelial differentiation, focusing on mucus and ciliated cells, using an in vitro asthma model. METHODS: Primary human airway basal cells from nonsmokers were cultured at air-liquid interface and treated with IL-13. We evaluated the effects of LABA, LAMA, and ICS by histological, molecular, and SEM analyses. RESULTS: IL-13 treatment increased mucus cells and reduced ciliated cells, though ciliation remained observable. LABA and ICS showed a tendency to promote goblet cell metaplasia and upregulate MUC5AC gene expression in some contexts, while LAMA mitigated goblet cell metaplasia without increasing mucin. LAMA also significantly enhanced FOXJ1 gene expression and restored ciliated structure and function more effectively. SEM and motion analysis confirmed better recovery of cilia length, density, and movement with LAMA. CONCLUSIONS: In this in vitro asthma-mimic model, LAMA suppresses mucus overproduction and promotes epithelial recovery, offering insights into its potential benefits for airway remodeling. These findings suggest that LAMA inhalation therapy may contribute to airway epithelial homeostasis, providing a novel perspective for its role in asthma management that warrants further investigation in more complex in vivo and clinical studies.

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