Does ambient PM2.5 reduce the protective association of leisure-time physical activity with mortality? A systematic review, meta-analysis, and individual-level pooled analysis of cohort studies involving 1.5 million adults

Abstract Background This study assessed whether higher levels of fine particulate matter (PM 2.5 ) reduce the protective effects of leisure-time physical activity (LTPA) on all-cause, cardiovascular, and cancer mortality, and explored the PM 2.5 threshold beyond which attenuation occurs. Methods We conducted two complementary investigations. First, a systematic review and meta-analysis (per PRISMA guidelines) identified eligible cohort studies from PubMed, Web of Science, Embase, and SPORTDiscus (from inception to 6 January 2025) that examined the independent or joint associations of LTPA and PM₂.₅ with mortality among adults (≥ 18 years). Second, an individual-level pooled analysis using harmonized data from three cohorts was performed using Cox regression modeling to assess the associations observed in the meta-analysis. Results In Study One, a total of seven cohort studies ( n = 1,515,094; deaths = 115,196) were included in the meta-analysis, revealing that the reduction in all-cause mortality risk diminished with higher PM 2.5 exposure. Meeting the recommended LTPA level (7.5–15 MET-h/week) reduced all-cause mortality risk by approximately 30% at PM 2.5 < 25 μg/m 3 but only 12–15% at 25 + μg/m 3 . Study Two (three cohorts; n = 869,038; deaths = 45,080) confirmed this pattern. Individuals meeting the recommended LTPA level (7.5–15 MET-h/week) had a lower risk of all-cause mortality compared to those in the highest-risk group (reference: < 1 MET-h/week and PM 2.5 : 35–50 μg/m 3 ). Hazard ratios (HRs) varied by PM 2.5 exposure, with lower HRs indicating a greater protective effect: 35–50 μg/m 3 (HR = 0.75, 95% CI: 0.61–0.93), 25–35 μg/m 3 (HR = 0.67, 95% CI: 0.57–0.79), 15–25 μg/m 3 (HR = 0.34, 95% CI: 0.29–0.39), 10–15 μg/m 3 (HR = 0.34, 95% CI: 0.28–0.41), and < 10 μg/m 3 (HR = 0.30, 95% CI: 0.25–0.37). Higher levels of LTPA were generally associated with lower all-cause and cause-specific mortality across most PM₂.₅ exposure categories, but the protective effects were attenuated at PM₂.₅ levels 25 + μg/m 3 for all outcomes and became non-significant for cancer mortality at 35–50 μg/m 3 . Conclusions LTPA is beneficial for all-cause, cardiovascular, and cancer mortality even at relatively high PM 2.5 levels, with greater benefits observed under cleaner air conditions. However, its protective effects are attenuated at 25 + μg/m 3 for all outcomes and become less evident at 35–50 μg/m 3 , particularly for cancer mortality. PROSPERO Registration Number CRD42023395364.