Background: Previous studies have reported epigenetic changes in lung tissue or blood of COPD patients but whether the relationship of methylation changes with the severity of airflow limitation is similar or different in both tissues is unknown.

Methods: DNA was extracted from blood (n=269) and lung tissue (n=140) of COPD patients with different levels of airflow limitation (FEV₁ % ref.). DNA methylation was assessed with the EPIC array (Illumina). CpG-sites associated with FEV₁ %ref. in blood and lung tissue, were determined using multivariate regression adjusted for age, sex, smoking status and packs/year.

Results: Both in blood and lung tissue, 4,979 CpGs were associated with FEV₁% ref. (FDR<0.05). Interestingly, 98% of these CpGs presented an opposite association with FEV₁% ref. between the two tissues. Annotated genes showing a negative association with FEV₁% ref. in blood, but a positive association in lung tissue were enriched for ontologies related to actin organization, T cell differentiation, cell signaling and morphogenesis. Conversely, annotated genes with a positive association to FEV₁% ref. in blood (but negative in lung tissue) were enriched for cell junction assembly, cell-matrix adhesion and cell migration ontologies.

Conclusions: Blood and lung DNA share differentially methylated positions in relation to the severity of airflow limitation. However most of them present an opposite direction of effect suggesting that both tissues are differentially regulated.