Biological aging, a mediator between smoking and chronic obstructive pulmonary disease: evidence from a hospital-based cohort study in China

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity, with aging and smoking as key risk factors. However, the mediating role of biological aging in the smoking-COPD relationship has been rarely examined in Chinese populations. In this hospital-based cohort study, 1,269 Chinese adults aged 40–84 years without COPD were enrolled. We developed Klemera-Doubal method-biological age (KDM-BA) using 11 routine clinical biomarkers. KDM-BA acceleration (KDM-BAAc) was calculated by regressing KDM-BA on chronological age (CA). Three Cox models were used to assess the association between KDM-BAAc and COPD risk. Restricted cubic spline models were used to evaluate the dose–response relationship between KDM-BAAc and COPD risk. Counterfactual mediation analysis was used to quantify BA acceleration’s mediating role in smoking-COPD association. Over a mean follow-up of 3.4 years, 47 incident COPD cases occurred (incidence rate: 10.90/1000 person-years). Biological older was associated with higher COPD incidence [15.94 vs. 7.00/1,000 person-years; rate ratios (RR) = 2.28, 95% confidence intervals (95% CI) = 1.22–4.40]. Each 1-year increase in KDM-BAAc elevated COPD risk by 7% [fully adjusted hazard ratio (HR) = 1.07, 95% CI = 1.03–1.12]. Dose–response relationships were found between biological aging and COPD (fully adjusted P for overall = 0.003). KDM-BAAc mediated 14.3% (fully adjusted) of smoking's effect on COPD. Results remained robust across sensitivity analysis. Accelerated biological aging is associated with increased COPD risk and serves as a significant mediator in the smoking-COPD relationship among Chinese adults.