Association Between Exposure to Air Pollutant Mixture and Risk of Inflammatory Bowel Disease: Modifying Effects of...

Background: Although air pollution is increasingly considered an environmental hazard for inflammatory bowel disease (IBD), existing evidence predominantly relies on single-pollutant models that fail to capture mixed exposures, with modifying effects of individual lifestyle and residential environments remaining largely unexplored. Methods: We conducted a prospective cohort study using UK Biobank data, including 323,608 participants followed for incident IBD. Annual mean concentrations of five air pollutants [nitrogen dioxide (NO₂), nitrogen oxides (NO_x), and PM with aerodynamic diameters of ≤2.5, 2.5-10, and ≤10 μm (PM_2.5, PM_2.5-10, PM₁₀)] and greenspace percentage within 300 m and 1000 m buffers were assigned to each participant's residential address. A healthy lifestyle score was defined by five factors: smoking status, alcohol consumption, physical activity, sleep patterns, and dietary quality. Cox proportional hazards models with quantile g-computation (QGC) were employed to examine associations between single- and mixed-air-pollutant exposures and IBD risk. Stratified analyses were performed by healthy lifestyle, lifestyle score, and greenspace percentage. Results: During the follow-up period, 1649 and 805 participants developed ulcerative colitis (UC) and Crohn's disease (CD), respectively. Single-pollutant models suggested that exposures to most air pollutants were substantially associated with increased risk of IBD, and the association strengths were more pronounced for UC than for CD. QGC analyses indicated that the hazard ratios (HR) of IBD risk were 1.068 (95%CI: 1.018-1.121) for each one-quantile increase in the air pollutant mixture, with NO₂ weighted as the largest contributor. High physical activity was significantly linked to an attenuated UC-pollutant mixture association. Conclusions: This study found that exposure to an air pollutant mixture was associated with increased risk of IBD, especially for UC, with NO₂ contributing the largest effect size. The certain attenuated air pollution effects of healthy lifestyles and residential greenspaces underscore the need for integrated public health strategies with environmental management.