Background: Few studies examining the associations between long-term exposure to ambient air pollution and mortality have considered multiple pollutants when assessing changes in exposure due to residential mobility during follow-up.

Objective: We investigated associations between cause-specific mortality and ambient concentrations of fine particulate matter (≤ 2.5 μm; PM_2.5), ozone (O₃), and nitrogen dioxide (NO₂) in a national cohort of about 2.5 million Canadians.

Methods: We assigned estimates of annual concentrations of these pollutants to the residential postal codes of subjects for each year during 16 years of follow-up. Historical tax data allowed us to track subjects’ residential postal code annually. We estimated hazard ratios (HRs) for each pollutant separately and adjusted for the other pollutants. We also estimated the product of the three HRs as a measure of the cumulative association with mortality for several causes of death for an increment of the mean minus the 5th percentile of each pollutant: 5.0 μg/m³ for PM_2.5, 9.5 ppb for O₃, and 8.1 ppb for NO₂.

Results: PM_2.5, O₃, and NO₂ were associated with nonaccidental and cause-specific mortality in single-pollutant models. Exposure to PM_2.5 alone was not sufficient to fully characterize the toxicity of the atmospheric mix or to fully explain the risk of mortality associated with exposure to ambient pollution. Assuming additive associations, the estimated HR for nonaccidental mortality corresponding to a change in exposure from the mean to the 5th percentile for all three pollutants together was 1.075 (95% CI: 1.067, 1.084). Accounting for residential mobility had only a limited impact on the association between mortality and PM_2.5 and O₃, but increased associations with NO₂.

Conclusions: In this large, national-level cohort, we found positive associations between several common causes of death and exposure to PM_2.5, O₃, and NO₂.