Background

A number of population-based studies have investigated long-term effects of nitrogen dioxide (NO₂) on mortality, while great heterogeneities exist between locations and studies. In highly populated countries in Asia, cohort evidence for NO₂-mortality association was extensively sparse. This study primarily aimed to quantify longitudinal association of ambient NO₂ exposure with all-cause mortality in Chinese adults.

Methods

A national cohort of 30,843 adult men and women were drawn from 25 provincial regions across mainland China, and followed up from 2010 through 2018. Participants’ exposures to ambient air pollutants (i.e., NO₂, particulate matter with aerodynamic diameter ≤2.5 μm [PM_2.5], and ozone [O₃]) were assigned according to their residential counties at baseline, through deriving monthly estimates from high-quality gridded datasets developed by machine learning methods. Cox proportional hazards models with time-varying exposures were utilized to assess the association of all-cause mortality with long-term exposure to ambient NO₂. NO₂-attributable deaths in China were estimated by province and county for years 2010 and 2018, with reference to the counterfactual exposure of 6.9 μg/m³ (the lowest county-level average in this cohort).

Results

We observed a total of 1662 deaths during 224020.2 person-years of follow-up (median 8.1 year). An approximately linear NO₂-mortality relation (p=0.273 for nonlinearity) was identified across a broad exposure range of 6.9–57.4 μg/m³. Per 10-µg/m³ increase in annual NO₂ exposure was associated with an hazard ratio of 1.127 (95% confidence interval: 1.042–1.219, p<0.003) for all-cause mortality. Risk estimates remained robust after additionally adjusting for the confounding effects of co-pollutants (i.e., PM_2.5 or O₃). Subgroup analyses suggested a significant effect modification by sex (p=0.024), and only men suffered from NO₂-related death risk. In 2018, 1.65 million deaths could be attributed to ambient NO₂ exposure (national average 17.3 µg/m³) in China, representing a decrease of 4.3% compared with the estimate of 1.72 million in 2010 (20.5 µg/m³).

Conclusions

This cohort study provided national evidence for elevated risk of all-cause mortality associated with long-term exposure to ambient NO₂ in Chinese adults. Future longitudinal investigations in China are warranted to differentiate the effects of NO₂ exposure on cause-specific mortality outcomes.