Joint Associations of Outdoor Nitrogen Dioxide and Temperature with Incident Adult-Onset Asthma in the United States

Background: Nitrogen dioxide (NO2) is a surrogate for traffic and industrial air pollution associated with adverse respiratory outcomes. Whether elevated NO2 and temperature jointly influence adult-onset asthma (AOA) risk is unclear, especially among subgroups with varying lifestyle and exposure profiles. We investigated further in the prospective All of Us research program. Methods: Among 596,926 U.S. participants who consented to electronic health record release, annual average NO2 concentrations from satellite data were linked to residential locations for 376,535 individuals. We used multivariable Cox regression to estimate associations between NO2, temperature, and incident AOA, adjusting for co-pollutants and potential confounders. We analyzed 4-category cross-classification variables between NO2 (high>75th percentile vs. low<=75th percentile) and maximum or average temperature (high>median vs. low<=median). We also stratified by sex, age, income, and smoking status. Additive interactions were estimated using Relative Excess Risk due to Interaction, Attributable Proportion, and Synergy Index. Results: We identified 10,413 incident AOA cases over an average 4-year follow-up. Participants with the highest categories of NO2 and temperature exposure had significantly higher risk compared to those with the lowest (HRHigh NO2 x High Max. Temp.=1.37, 95%CI:1.26-1.49; HRHigh NO2 x High Average Temp.=1.49, 95%CI:1.38-1.61). The joint association of high NO2 and high maximum temperature was more pronounced among ever-smokers (HR=1.59, 95%CI:1.40-1.81) than never-smokers (HR=1.26, 95%CI:1.13-1.41). Interaction analyses supported super-additive interactions of high NO2 and high average temperature on AOA risk, particularly among ever smokers, lower-income participants, and younger adults. Conclusion: Our findings highlight the respiratory health threat of long-term joint exposure to elevated NO2 and average temperature, particularly among vulnerable subgroups.