Short-term Exposure to Nitrogen Dioxide May Increase Risk of Death From Respiratory Disease

March 27, 2021
Skylar Jeremias

Exposure to nitrogen dioxide (NO2), an air pollutant generated from automobiles, may increase risk of mortality, even if the exposure amount is well below regulatory limits, investigators concluded.

Short-term exposure to nitrogen dioxide (NO2) was found to have a linear association with increased risk of total, cardiovascular, and respiratory death, according to a recent study published in BMJ.

“Although reduction of NO2 to zero is infeasible, our analysis provides insight into the public health benefits of substantial reductions in NO2, suggesting considerable health benefits from stricter control of NO2 emissions and tightening of the regulatory limits of NO2 in future revisions of [World Health Organization] air quality guidelines,” wrote the investigators.

The results provided key evidence to confirm disputed results generated from previous studies that have found short-term exposure for NO2 to have a connection with mortality and morbidity.

NO2 is a common air pollutant known to be a precursor to ground level ozone (O3) and result in worse population health. Most NO2 results from human activity, largely stemming from fuel combustion and automobile traffic. NO2 is also involved in the secondary formation of particulate matter (PM), which are solid and liquid particles suspended in the air that can be hazardous if breathed in.

In 2008 and 2016, the United States Environmental Protection Agency conducted the Integrated Science Assessment, a review that concluded a causal relationship between NO2 exposure and respiratory effects. The review highlighted knowledge gaps surrounding NO2 and resulted in the adoption of air quality guidelines that varied between governments.

Several studies have attempted to investigate if an association exists between NO2 and mortality. However, most didn’t take into account cause specific mortality, such as respiratory and cardiovascular outcomes, and did not clarify possible features of associations, including nonlinearity, thresholds, and lag structures. Furthermore, they were often performed in only 1 city or country and thus, lacked generalizability.

For the present study, the investigators gathered health and environmental information from the Multi-City Multi-Country database, which allowed for ground level NO2 measurements to analyzed in 398 cities across 22 countries or regions.

During the 1973 to 2018 study period, there were 62.5 million deaths from total or nonexternal causes, including 19.7 million (31.4%) deaths due to cardiovascular disease and 5.5 million (8.8%) due to respiratory diseases.

On average, the median annual mean NO2 concentration was 26.9 μg/m3. The median average annual temperature was 14.4℃. NO2 was found to be negatively correlated with mean temperature and relative humidity (Pearson r = -0.29 and -0.15, respectively).

The risk of total mortality at increased by 0.46% (95% CI, 0.36-0.57) for every 10 μg/m3 increased in NO2 concentration for all of the cities included in the study. Across 362 cities, the corresponding increases were 0.37% (95% CI, 0.22-0.51) for cardiovascular mortality and 0.47 (95% CI, 0.21-0.72) for respiratory mortality.

“This result suggests that NO2 is associated with considerable health risks even at levels below health based standards and guidelines, including the current WHO air quality guidelines,” wrote the investigators.

When adjusting for other pollutants, including sulfur dioxide, O3, and carbon monoxide, NO2-related mortality increased slightly. However, the effect decreased 19% (P = .08) after adjusting for PM with a diameter of 10 microns or less and 21% (P = .08) when adjusting for finer PM with a diameter of less than 2.5 micrometers.

The association between NO2 and the 3 types of mortality analyzed did not change when the investigators adjusted for relative humidity or seasonal differences, which increased similarly between cold (0.51%, 95% CI, 0.41-0.60, P = .68) and warm seasons (0.43%, 95% CI, 0.31-0.50, P = .68).

Several limitations were identified, including the inability to generalize globally due to most of the data coming from developed areas and the inability to completely rule out ecological fallacy and exposure miscalculations. Additionally, the investigators could not account for slight changes in air pollution measurements and there may have been a potential underestimation of the potential effect of NO2 on total mortality due to all of the health outcomes being obtained from primary causes.

“These findings contribute to a better understanding of how to optimise public health actions and strategies to mitigate air pollution,” noted the investigators.


Meng X, Liu C, Chen R, et al. Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality: Multilocation analysis in 398 cities. BMJ. Published online March 24, 2021. Accessed March 26, 2021. doi: 10.1136/bmj.n534