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 PM_2.5, 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 PM_2.5 compounds. Utilizing exposomic characterization of 1327 compounds in personal PM_2.5 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 PM_2.5, 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 PM_2.5 components containing an unsaturated ring, highlighting the additive risks from an air pollution mixture.