A population-based cohort study of respiratory disease and long-term exposure to iron and copper in fine particulate air pollution and their combined impact on reactive oxygen species generation in human lungs

Metal components in fine particulate matter (PM_2.5) from nontailpipe emissions may play an important role in underlying the adverse respiratory effects of PM_2.5. We investigated the associations between long-term exposure to iron (Fe) and copper (Cu) in PM_2.5 and their combined impact on reactive oxygen species (ROS) generation in human lungs, and the incidence of asthma, chronic obstructive pulmonary disease (COPD), COPD mortality, pneumonia mortality, and respiratory mortality. We conducted a population-based cohort study of ∼0.8 million adults in Toronto, Canada. Land-use regression models were used to estimate the concentrations of Fe, Cu, and ROS. Outcomes were ascertained using validated health administrative databases. We found positive associations between long-term exposure to Fe, Cu, and ROS and the risks of all five respiratory outcomes. The associations were more robust for COPD, pneumonia mortality, and respiratory mortality than for asthma incidence and COPD mortality. Stronger associations were observed for ROS than for either Fe or Cu. In two-pollutant models, adjustment for nitrogen dioxide somewhat attenuated the associations while adjustment for PM_2.5 had little influence. Long-term exposure to Fe and Cu in PM_2.5 and estimated ROS concentration in lung fluid was associated with increased incidence of respiratory diseases, suggesting the adverse respiratory effects of nontailpipe emissions.