Epigenetic analysis of COPD-patient derived airway organoids

Epigenetic mechanisms control gene expression and play a central role in regulating cellular processes involved in the development and progression of chronic lung diseases, including chronic obstructive pulmonary disease (COPD). In this study, we differentiated basal cells from individuals with and without COPD into 3D airway organoids and performed epigenetic profiling using the Infinium MethylationEPIC array. Promoters of inflammation-associated genes (e.g., TNFAIP2 ), which are expressed in secretory cell clusters of the airway organoids, were hypomethylated in both basal cells and organoids derived from individuals with COPD. Smoking was associated with global hypomethylation, including at the promoters of genes involved in airway secretions (e.g., BPIFA2 ). GSEA analysis revealed that genes with hypomethylated promoters in smoker-derived basal cells and organoids were significantly enriched among those highly expressed in secretory cells of differentiated organoids. Our findings reveal that smoking and COPD are associated with epigenetic alterations, including promoter hypomethylation of inflammation- and secretion-related genes, which are enriched in secretory cell populations of airway organoids. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany