Omega-3 Modify the Adverse Effects of Long-Term Exposure to Ambient Air Pollution on the Incidence of Chronic Obstructive Pulmonary Disease: Evidence from a Nationwide Prospective Cohort Study

We aim to assess the modification effects of omega-3 polyunsaturated fatty acid (PUFA) levels on relationships between long-term air pollutants exposure and chronic obstructive pulmonary disease (COPD) risk. A total of 82,706 nonsmokers were finally included in the UK Biobank. The concentrations of circulating omega-3 PUFA (including total omega-3 and docosahexaenoic acid [DHA]) were measured by using a targeted high-throughput nuclear magnetic resonance metabolomics platform. Land-use regression models were used to estimate concentrations of nitrogen dioxide (NO₂) and particulate matter (PM_2.5 and PM₁₀) for each individual. Additionally, systemic inflammation levels were assessed using the low-grade inflammation score (INFLA-score) to elucidate the potential mechanism. We noted that the observed effects could be modified by circulating omega-3 PUFA levels (P-interaction < 0.05). Specifically, the significant pollutants-COPD associations were mainly observed in the lower circulating omega-3 PUFA groups. In contrast, there was no statistical evidence for increased COPD risk associated with air pollutants in subjects with higher circulating omega-3 PUFA. Mediation analysis further indicated that circulating omega-3 PUFA modified the air pollution-associated COPD risk might partly by reducing systemic inflammation. In summary, circulating omega-3 PUFA may provide protection against the COPD risk caused by long-term exposure to air pollutants.