Long-term exposure to nitrogen dioxide and natural-cause and cause-specific mortality in Japan

Long-term exposure to air pollution is linked with increased risk of adverse health outcomes, but the evidence for the association between nitrogen dioxide (NO₂) and mortality is weak because of the inadequate adjustment of potential confounders and limited spatial resolution of the exposure assessment. Moreover, there are concerns about the independent effects of NO₂. Therefore, we examined the association between NO₂ long-term exposure and all-cause and cause-specific mortality.

We included participants who were enrolled in health checkups in Okayama City, Japan, in 2006 or 2007 and were followed until 2016. We used a land-use regression model to estimate the average NO₂ concentrations from 2006 to 2007 and allocated them to the participants. We estimated hazard ratios (HRs) for a 10-μg/m³ increase in NO₂ levels for all-cause or cause-specific mortality using Cox proportional hazard models.

After excluding the participants who were assigned with outlier exposures, a total of 73,970 participants were included in the analyses. NO₂ exposure was associated with increased risk of mortality and the HRs and their confidence intervals were 1.06 (95% CI: 1.02, 1.11) for all-cause, 1.02 (0.96, 1.09) for cardiopulmonary, and 1.36 (1.14, 1.63) for lung cancer mortality. However, the elevated risks became equivocal after the adjustment for fine particulate matter except lung cancer.

Long-term exposure to NO₂ was associated with increased risk of all-cause, cardiopulmonary, and lung cancer mortality. The elevated risk for lung cancer was still observable even after adjustment for fine particulate matter.