Composition-Specific Effects of PM_2.5 on Influenza-Like Illness: Independent Roles of Chemical Components and Mixture Profiles in a Multi-City Study

Background Short-term exposure to PM2.5 has been associated with respiratory infections, yet evidence on the health effects of its chemical components remains limited. Moreover, as PM2.5 components coexist as complex mixtures, it is unclear whether differences in compositional profiles contribute additional influenza-like illness (ILI) risk beyond the independent effects of individual components. Methods We analyzed weekly ILI surveillance data from 111 sentinel hospitals in 17 cities of Hubei, China (2021-2024), together with weekly PM2.5 concentrations and chemical components (sulfate, nitrate, ammonium, organic matter, and black carbon) from the TAP dataset and meteorological variables from ERA5-Land. To evaluate the associations of individual PM2.5 components and overall compositional profiles with ILI, we applied K-means clustering to identify distinct PM2.5 profiles and fitted city-specific quasi-Poisson models, which were then pooled using DerSimonian-Laird method. Results Among 2,804,416 ILI cases, PM2.5 mass was positively associated with weekly ILI, with a pooled RR of 1.041 (95% CI: 1.028-1.054) per 10 µg/m3 increase. Positive associations were also observed for sulfate, nitrate, ammonium, OM, and BC. Three compositional profiles were identified (SID: secondary inorganic-dominated, MOD: mixed organic-dominated; ORM: Other-rich mixed). After adjustment for PM2.5 and its component concentrations, exposure to ORM was associated with an extra 19.6% higher ILI risk than SID (RR = 1.196, 95% CI: 1.096-1.305), while exposure to the MOD was associated with an 8.9% higher ILI risk (RR = 1.089, 95% CI: 1.008-1.176). Conclusions These findings suggest that PM2.5 related ILI risk may depends not only on overall mass concentration and individual components, but also on compositional profiles. Incorporating PM2.5 mixture heterogeneity may improve assessment of air pollution related respiratory health risks.