Ozone Enhances the Inflammation Effects of PM2.5 Components Based on an Exposomic Approach in a Panel Study

Ozone (O3) has been implicated in exacerbating the adverse health effects of ambient PM2.5, yet the role of chemical composition in this process remains unclear. This study aimed to systematically evaluate how the use of O3 enhances inflammation induced by PM2.5 compounds. Utilizing exposomic characterization of 1327 compounds in personal PM2.5 from a panel study of elderly urban residents, our analysis revealed that O3 enhanced associations of pro-inflammatory biomarkers, i.e., exhaled nitric oxide, exhaled interleukin-6, serum interleukin-6, serum interleukin-1β, serum tumor necrosis factor-α, and urinary malondialdehyde, with 149, 130, 158, 190, 67, and 20 compounds in PM2.5, respectively. Most of these compounds were monocyclic and polycyclic aromatics, nitrated aromatics, and terpenoids. Their structural features indicated the presence of unsaturated double bonds in aromatics and terpenoids, driving a 1.3–5.6-fold change in O3 interaction values compared with those of compounds lacking such bonds; the interactions presumably occur in the lungs. Among species screened for O3 enhancement, in silico toxicokinetic analysis employing a random forest approach suggested the activation of cytochrome P450 1A2 and estrogen receptor as key physiological pathways. Overall, this study provides initial evidence demonstrating that O3 exacerbates the pro-inflammatory effects of PM2.5 components containing an unsaturated ring, highlighting the additive risks from an air pollution mixture.