Long-term NO₂ exposure and mortality: A comprehensive meta-analysis

In response to the World Health Organization's (WHO) revised annual mean nitrogen dioxide (NO2) standard from 40 mu g/m(3) to 10 mu g/m(3), reflecting the growing evidence linking long-term exposure to ambient NO2 and excess mortality, we conducted a comprehensive meta-analysis incorporating 11 new studies published since the WHO analysis. Our investigation involved a systematic search of three major databases (PubMed, Web of Science, and Scopus) for articles published until July 1, 2022. We employed random effects models to calculate summarized risk ratios (RR) along with 95% confidence intervals (CIs) for overall and subgroup analyses. Sensitivity analyses were conducted to assess result robustness, and publication bias was evaluated using funnel plots and Egger's linear regression. Out of 2799 identified articles, 56 were included in our meta-analysis. The findings indicate a heightened risk of all-cause, cardiovascular, and respiratory mortality associated with long-term exposure to ambient NO2, with pooled RR values of 1.03 (95% CI: 1.02, 1.05), 1.07 (95% CI: 1.04, 1.10), and 1.03 (95% CI: 1.02, 1.05) per 10 mu g/m(3) increase, respectively. Substantial heterogeneity (I-2 = 84%-96%) among studies was observed. Subgroup analysis revealed significantly elevated RR values in Asia and Oceania (p-value <0.05). The aggregated values for all-cause and cardiovascular mortality were slightly larger than those reported in previous studies. Our study emphasizes the imperative to develop more patient cohorts and conduct age-refined analyses to explore the impact of existing chronic diseases on these associations. Further, additional cohorts in Asia and Oceania are essential to fortify evidence in these regions. Lastly, we recommend using fused multi-source data with higher spatiotemporal resolution for individual exposure representation to minimize heterogeneity among studies in future research.