In Utero and Early-Life Exposure to Tobacco Smoke, Genetic Risk, and Chronic Obstructive Pulmonary Disease Incidence in Adulthood

INTRODUCTION: This study aimed to evaluate whether in utero and early-life tobacco exposure and genetic factors jointly contribute to incident chronic obstructive pulmonary disease (COPD). METHODS: A total of 412 050 participants without COPD at baseline were included. We assessed the associations of in utero tobacco exposure, age of smoking initiation, and their interactions with joint COPD polygenic risk scores (PRSs) with COPD risk using Poisson regression models. RESULTS: Participants with in utero tobacco exposure exhibited a higher risk of COPD (adjusted relative risk [aRR], 1.29; 95% confidence intervals [CIs], 1.25 to 1.33) compared to participants without in utero tobacco exposure. Compared with nonsmokers, the aRRs (95% CIs) of COPD risk for smoking initiation during adulthood, adolescence, and childhood were 4.23 (4.05 to 4.42), 5.17 (4.95 to 5.38), and 7.01 (6.68 to 7.36), respectively (ptrend < .001). Significant interactions were observed between in utero tobacco exposure, age of smoking initiation, and the genetic risk. Participants with both in utero tobacco exposure and smoking initiation during childhood had the highest risk of COPD (aRR, 9.04, 95% CI: 8.44 to 9.69; pmult = .006, padd < .001) compared to nonsmokers without in utero tobacco exposure. Furthermore, compared to non-smokers with low genetic risk, individuals with high genetic risk and childhood smoking initiation exhibited the greatest risk of COPD (aRR, 8.29, 95% CI, 7.65 to 8.99; padd < .001). CONCLUSIONS: Exposure to tobacco smoke in utero and during early life significantly increased the risk of COPD in adulthood, irrespective of genetic predisposition. These findings underscore the importance of early-life smoking prevention to mitigate the risk of developing COPD in adulthood. IMPLICATIONS: In utero tobacco exposure increased offspring COPD risk in middle and old age. Regardless of genetic background, early tobacco exposure elevates the risk of COPD. Findings are derived from a large prospective cohort study and a representative database survey.