Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: multilocation analysis in 398 cities

Objective: To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting: 398 cities in 22 low to high income countries/regions. Main outcome measures: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results: On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.

What is already known on this topic: Evidence for the short term association between ambient nitrogen dioxide (NO2) and mortality is limited, especially for cause specific associations Previous investigations have been mostly conducted in a small number of locations that cover limited geographical areas, and use different study designs and modelling approaches that lead to heterogeneous results What this study adds: This large multilocation study in 398 cities found that each 10 μg/m3 increase in NO2 concentrations on lag 1 day (previous day) was significantly associated with increased risk of total (0.46%), cardiovascular (0.37%), and respiratory (0.47%) mortality The concentration-response curves were almost linear without discernible thresholds even below the current WHO air quality guidelines, suggesting a need to revise the currently recommended values The uniform analytical approach allows a direct comparison of estimates across global regions,