Short-term exposure to PM2.5 constituents in relation to epilepsy hospitalization: A time-stratified case-crossover study with exploratory adverse outcome pathway analysis.

Evidence on the association between ambient air pollution, especially PM2.5 constituents, and epilepsy remains limited, and the underlying biological mechanisms remain poorly understood. We aimed to investigate the short-term effects of particulate and gaseous pollutants on epilepsy hospitalization and explore biologically plausible pathways using an adverse outcome pathway (AOP) framework. We conducted an individual-level time-stratified case-crossover study including 4,350 epilepsy hospitalizations. Daily exposures to ambient air pollutants and PM2.5 constituents were assigned at the residential level. Conditional logistic regression was used to estimate the percentage change in epilepsy hospitalization associated with an interquartile range (IQR) increase. To explore potential mechanisms, shared targets were identified using the CTD, GeneCards, and GTEx databases, followed by protein-protein interaction, hub gene, GO/KEGG enrichment. PM2.5 and its constituents were positively associated with epilepsy hospitalization at lag 6. For an IQR increase in exposure, the percentage changes in hospitalization were 7.09%-7.94% for PM2.5 and its constituents. SO2 showed a significant positive association at lag 6, with a 5.52% increase in hospitalization. Stratified analyses showed that these associations statistically significant among individuals aged ≥18 years, female patients, during the cool season, and in eastern China. The AOP-informed analysis provided exploratory, hypothesis-generating biological context that identified candidate pathways linking PM exposure to epilepsy-related abnormalities, including glutamate metabolism, Ca2+ dynamics, and maladaptive synaptic plasticity; however, these findings do not establish causal mechanisms. Short-term exposure to PM2.5 was significantly associated with increased epilepsy hospitalization. These findings suggest that fine particulate pollution may be important environmental triggers for epilepsy exacerbation.