Long-term exposure to ambient air pollution and circulating white blood cell homeostasis among adults in China: Time-window-specific associations and the mediating role of fasting blood glucose.
Abstract
Long-term exposure to ambient air pollution perturbs white blood cell (WBC) homeostasis through inflammatory pathways. However, its pollutant- and time-window-specific, mixture-related associations with WBC counts, and whether metabolic dysfunction mediates them, remain uncertain. We conducted a retrospective cohort study of 29,603 adults who underwent routine health examinations at Liangshan General Hospital between 2016 and 2024. Daily concentrations of six air pollutants were assigned to geocoded residential addresses and aggregated into one-month, six-month, one-year, and two-year average exposures before examination. Exposure-response associations were examined using single-pollutant mixed-effect models. Quantile g-computation and Bayesian kernel machine regression were applied to assess mixture effects and each pollutant's direction and contribution, while exploratory mediation analysis quantified the extent to which fasting blood glucose (FBG) accounted for pollutant-WBC associations. Associations were strongest for six-month average exposures. Per IQR increase in CO, NO2, PM10, PM2.5 and SO2, WBC counts changed by -0.206×109/L (95% CI: -0.237, -0.174), -0.231×109/L (-0.270, -0.192), -0.349×109/L (-0.391, -0.307), -0.503×109/L (-0.552, -0.454) and -0.216×109/L (-0.242, -0.191), respectively, whereas O3 was positively associated with WBC counts. Mixture analyses indicated a time-window-dependent signal, with particulate matter dominant in the negative association in the six-month window, whereas the dominant negative contributor shifted to SO2 in the two-year window. Exploratory analyses suggested that FBG accounted for part of the associations between several pollutants and WBC counts (4.97%-10.98%). The subgroups identified as most vulnerable were overweight, urban, and after-COVID-19 participants. These findings suggest pollutant- and exposure-window-specific changes in WBC homeostasis, with glycaemic regulation contributing modestly to pollution-related immune alterations.