Numerous existing studies reported the negative impacts of outdoor nitrogen dioxide (NO2) on respiratory mortality. However, the evidence of related high-risk populations was considerably limited, especially associated with ages, causes of death, and district-level characteristics. In addition, most earlier studies were based on monitored areas, thus previous risk estimates of NO2 could be biased to provide nationwide risk estimates and high-risk populations. Therefore, this study performed a nationwide time-stratified case-crossover study to evaluate the association between short-term ambient NO2 and respiratory mortality in South Korea (2015–2019). A machine learning-ensemble daily NO2 prediction model was used to cover unmonitored areas. To examine high-risk populations, we assessed NO2 risk estimates by age group, sex, cause of mortality, and district-level characteristics. In the total population, NO2 was weakly associated with increased mortality risk due to respiratory disease (OR [odds ratio]: 1.011, 95% CI [confidence interval]: 0.995–1.027), and the association became evident only in individuals aged 80 y or older (1.022, 1.000–1.044), especially related to pneumonia. Further, in people aged 60–69 years, NO2 was marginally associated with mortality for chronic lower respiratory diseases. Lower district-level socioeconomic status and medical services were marginally related to higher respiratory mortality risks related to NO2. The excess respiratory mortality fractions and YLL (year of life lost) attributable to NO2 were 4.13% and 93,851.63 years, and around 70% of the excess deaths were due to noncompliance with the World Health Organization air quality guidelines (daily average NO2 > 25 µg/m3). This study provides evidence for high-risk populations and the appropriateness of target-specific action plans against NO2. In addition, based on the excess death estimates, we suggest stricter NO2 standards are required.
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