Abstract
BACKGROUND: There has been limited research to date comprehensively assessing the effects of in utero tobacco exposure, age of smoking initiation and environmental pollution on the incidence of chronic obstructive pulmonary disease (COPD). METHODS: The participants in the current study were drawn from the UK Biobank cohort. 274,330 participants were included for analyses of in utero tobacco exposure and incident risk of COPD, and 306,080 were analyzed for age of smoking initiation and incident risk of COPD. In utero tobacco exposure was determined by maternal smoking during pregnancy. According to smoking habits, participants were classified as non-smokers, late-onset smokers (age of smoking initiation ≥ 15 years), or early-onset smokers (age of smoking initiation < 15 years). Environmental pollution is classified into low, medium, and high Environmental Pollution Score (EPS) groups. A Cox proportional hazard regression model was used to evaluate the effects of in utero tobacco exposure, age of smoking initiation, and environmental pollution on COPD incidence. The combined effects and interactions among in utero tobacco exposure, age of smoking initiation, and environmental pollution on COPD incidence were also examined. RESULTS: Over a median follow-up period of 12.96 years, 9054 and 10,301 participants were diagnosed with COPD based on in utero tobacco exposure and age of smoking initiation, respectively. Hazard ratios (HRs; 95% confidence intervals [CIs]) of COPD risk among early-onset smokers with in utero tobacco exposure, participants with in utero tobacco exposure and high EPS, early-onset smokers with high EPS, and early-onset smokers with high EPS and in utero tobacco exposure were 3.92 (3.54, 4.31), 1.25 (1.15, 1.35), 3.49 (3.11, 3.91), and 3.81 (3.26, 4.46), compared with non-smokers without in utero tobacco exposure, participants without in utero tobacco exposure and low EPS, non-smokers with low EPS, and non-smokers with low EPS and without in utero tobacco exposure, respectively. Furthermore, additive interactions among late-onset smokers and intermediate/high EPS were observed [relative excess risk due to the interaction (95% CI): 0.26 (0.07, 0.45) and 0.34 (0.15, 0.52)]. CONCLUSIONS: Our findings suggest that in utero tobacco exposure, early-life smoking, and environmental pollution independently and jointly increase the incidence of COPD. CLINICAL TRIAL NUMBER: Not applicable.