Mixture effects of multiple environmental factors on chronic obstructive pulmonary disease risk Trajectories: Evidence from Pearl River cohort in China

• Exposure to multiple environmental factors may increase the risk of COPD progression to death by 29.9%. • NO 2 and SO 4 2− were the primary environmental contributors to COPD progression. • Balanced and ecology-dominant patterns were linked to 8–––18% lower risks across COPD progression. COPD may be influenced by complex environmental interactions. Current evidence is limited to isolated stages and is lacking on the effects of mixture exposures. This study assessed the effects of environmental mixtures on COPD risk trajectories. We analyzed the impact of mixture exposures (air pollution, meteorological factors, built environment features) on COPD hospitalization/mortality for 67,235 participants. We applied Weighted Quantile Sum regression to quantify mixture effects and mixture contributions. In the WQS regression analysis, each quartile increase in the WQS index was associated with a 29.9% higher risk of transitioning from hospitalization to death, with NO 2 (21.8%) and SO 4 2− (19.4%) contributing the most. No significant associations were observed for the transition from baseline to hospitalization or the transition from baseline to death. Furthermore, we employed K-means clustering to identify distinct exposure patterns. Three exposure patterns were identified. Compared with the Urbanization-Dominant Pattern, the Urbanization-Ecology Balanced and Ecology-Dominant Patterns were inversely associated with transitions from baseline to hospitalization (17.5% and 9.0% lower risk, respectively) and to death (17.8% and 9.2% lower risk, respectively). The elderly had an 37.8% higher risk of the transition from hospitalization to death. Environmental mixtures significantly affect COPD trajectories. Controlling critical pollutants and optimizing ecological planning are essential for the COPD burden.