BACKGROUND: Epidemiological studies have consistently demonstrated a robust association between long-term exposure to air pollutants and respiratory diseases. However, establishing causal relationships remains challenging due to residual confounding in observational studies. In this study, Mendelian randomization (MR) analysis was used to explore the causal and epigenetic relationships between various air pollutants and common respiratory diseases. METHODS: We utilized a two-sample Mendelian randomization (TSMR) approach to explore the impact of PM RESULTS: TSMR analysis revealed that exposure to PM CONCLUSIONS: Our findings suggest that exposure to air pollutants may play a causal role in the development of respiratory diseases, with a potential role of epigenomic modifications emphasized. Strengthening comprehensive air pollution regulations by relevant authorities could potentially mitigate the risk of these diseases.