Chronic obstructive pulmonary disease (COPD), a complex disease with polygenetic tendency, is one of the most important health problems in the world. Recently, in the study of the pathogenesis of the COPD, epigenetic changes caused by environmental factors, such as DNA methylation, started to attract more attention than genetic factors. In this review, we discuss the main features of DNA methylation, such as DNA methyltransferases and the methylation sites that modulate the DNA methylation level, and their roles in COPD progression. Finally, to promote new ideas for the prevention and treatment of COPD, we focus on the potential of DNA methylation as a COPD therapeutic target.

Chronic obstructive pulmonary disease (COPD) was the third leading cause of death worldwide in 2019, with a significant disease burden. We conducted a nested case–control study using data from the China Metal-Exposed Workers Cohort Study (Jinchang Cohort) and assessed the associations of exposure to metals and tobacco smoking with the risk of COPD. We used the logistic regression model and the interaction multiplication model to assess the independent and combined effects of heavy metal and smoke exposure on COPD. The cumulative incidence of COPD was 1.04% in 21,560 participants during a median of two years of follow-up. The risk of COPD was significantly elevated with an increase in the amount of tobacco smoked daily (p < 0.05), the number of years of smoking (ptrend < 0.05), and the number of packs of cigarettes smoked per year (ptrend < 0.01). Compared with the low metal exposure group, the adjusted OR was 1.22 (95% CI: 0.85–1.76) in the medium exposure group (mining/production workers) and 1.50 (95% CI: 1.03–2.18) in the high exposure group; smoking and metal exposure had a combined effect on the incidence of COPD (pinteraction < 0.01), with an OR of 4.60 for those with >40 pack-years of smoking who also had the highest metal exposures. Both exposures to metals and smoking were associated with the risk of COPD, and there was an interaction between the two exposures for the risk of COPD.