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Objectives: Exercise may increase the inhaled amount of air pollutants and exacerbate the adverse health effects. We investigated the combined effects of chronic exposure to fine particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual exercise on C reactive protein (CRP), a sensitive marker of inflammation.Methods: We selected 40 209 Taiwanese adults who joined a standard medical screening programme between 2001 and 2016. The PM2.5 exposure was estimated at each participant's address using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. Mixed-effects linear regression models were used to investigate the associations of CRP with PM2.5 and exercise. An interaction term of PM2.5 and exercise was introduced in the models to test the modifying effects.Results: A greater amount of habitual exercise was associated with a decreased level of CRP, while a higher concentration of PM2.5 exposure was associated with an increased level of CRP. The inverse associations of habitual exercise with CRP were not modified by chronic exposure to PM2.5. The participants in the group with a low level of exercise and a high level of PM2.5 exposure exhibited a 19.1% higher level of CRP than those in the group with a high level of exercise and a low level of PM2.5 exposure (95% CI: 13.7% to 24.8%; p<0.001). The longitudinal and sensitivity analyses yielded similar results.Conclusions: Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower CRP level. Habitual exercise reduces CRP level regardless of the levels of chronic PM2.5 exposure. Our results support that habitual exercise is a safe approach for reducing systemic inflammation to improve cardiovascular health even for people residing in relatively polluted areas. [ABSTRACT FROM AUTHOR]