Long-term exposure to ambient ozone and adult-onset asthma: A prospective cohort study

Background: The association between long-term exposure to ozone (O₃) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. Objectives: To examine the causal association between long-term O₃ exposure and AOA. Methods: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O₃ exposure at participants’ residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O₃ exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. Results: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O₃ exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O₃ at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O₃ at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O₃ exposure and AOA risk, but not for low-level O₃ exposure. No significant associations between O₃ exposure and accidental injury were observed. Conclusion: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O₃ and increased risks of AOA.