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

BMJ. 2021 Mar 24;372:n534. doi: 10.1136/bmj.n534.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity*
  • Air Pollution / adverse effects*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / mortality*
  • Cities
  • Developed Countries / statistics & numerical data
  • Developing Countries / statistics & numerical data
  • Environmental Exposure / adverse effects
  • Global Health / statistics & numerical data*
  • Humans
  • Linear Models
  • Nitrogen Dioxide / toxicity*
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / mortality*
  • Urban Health / statistics & numerical data*


  • Air Pollutants
  • Nitrogen Dioxide