Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Previous studies have shown changes in DNA methylation in blood and lung tissue are associated with presence and severity of COPD. Little is known yet about DNA methylation changes in the airways in COPD and the relation with disease severity.

Aim: To assess whether the presence and severity of COPD are associated with changes in DNA methylation in the airways.

Methods: DNA methylation profiling (EPIC 850k array) and RNA sequencing was performed on bronchial biopsies obtained from 90 COPD patients and 21 non-COPD controls, mean age 61.3 and 50.2, mean FEV1 % predicted (%p) 71.5 and 92.7, all current smokers. Differential DNA was determined using linear models, followed by correlation analyses with FEV1%p and RV/TLC%p in the COPD subset. Differentially methylated sites were correlated with gene expression data, available in bronchial biopsies of the same subjects, using MatrixEQTL.

Results: Six differentially methylated CpG sites were identified between COPD and non-COPD individuals, none of which correlated with gene expression. In a sub analysis of COPD patients, 25 CpG sites were associated with FEV1%p and 554 CpG sites with RV/TLC%p. Two of the top DNA methylation sites that were hypermethylated with higher RV/TLC%p were cg11734183, and cg13421038 and these were associated with lower expression of RGMB and SFSWAP, genes involved in inflammation and growth respectively.

Conclusions: Our study identified an altered DNA methylation profile associated with the presence and severity of COPD. These findings provide a better understanding of the epigenetic changes involved in the pathogenesis of COPD.