Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM 2.5 Transition Metals and Oxidative Potential.

BACKGROUND: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O 3 and NO 2 ) and fine particulate air pollution (PM 2.5 ). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM 2.5 is more capable of causing oxidative stress. METHODS: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM 2.5 components and oxidative potential. O x exposures (i.e., the redox-weighted average of O 3 and NO 2 ) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O x and mortality outcomes across strata of transition metals and sulfur in PM 2.5 and three measures of PM 2.5 oxidative potential adjusting for possible confounding factors. RESULTS: Associations between O x and mortality were consistently stronger in regions with elevated PM 2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O x was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP GSH ) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP GSH levels below the median (interaction P value <0.001). CONCLUSION: Spatial variations in PM 2.5 composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases.

Association of Sulfur, Transition Metals, and the Oxidative Potential of Outdoor PM2.5 with Acute Cardiovascular Events: A Case-Crossover Study of Canadian Adults.

BACKGROUND: We do not currently understand how spatiotemporal variations in the composition of fine particulate air pollution [fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5)] affects population health risks. However, recent evidence suggests that joint concentrations of transition metals and sulfate may influence the oxidative potential (OP) of PM2.5 and associated health impacts. OBJECTIVES: The purpose of the study was to evaluate how combinations of transition metals/OP and sulfur content in outdoor PM2.5 influence associations with acute cardiovascular events. METHODS: We conducted a national case-crossover study of outdoor PM2.5 and acute cardiovascular events in Canada between 2016 and 2017 (93,344 adult cases). Monthly mean transition metal and sulfur (S) concentrations in PM2.5 were determined prospectively along with estimates of OP using acellular assays for glutathione (OPGSH), ascorbate (OPAA), and dithiothreitol depletion (OPDTT). Conditional logistic regression models were used to estimate odds ratios (OR) [95% confidence intervals (CI)] for PM2.5 across strata of transition metals/OP and sulfur. RESULTS: Among men, the magnitudes of observed associations were strongest when both transition metal and sulfur content were elevated. For example, an OR of 1.078 (95% CI: 1.049, 1.108) (per 10µg/m3) was observed for cardiovascular events in men when both copper and S were above the median, whereas a weaker association was observed when both elements were below median values (OR=1.019, 95% CI: 1.007, 1.031). A similar pattern was observed for OP metrics. PM2.5 was not associated with acute cardiovascular events in women. DISCUSSION: The combined transition metal and sulfur content of outdoor PM2.5 influences the strength of association with acute cardiovascular events in men. Regions with elevated concentrations of both sulfur and transition metals in PM2.5 should be examined as priority areas for regulatory interventions. https://doi.org/10.1289/EHP9449.

Predicting Spatial Variations in Multiple Measures of Oxidative Burden for Outdoor Fine Particulate Air Pollution across Canada.

Fine particulate air pollution (PM2.5) is a leading contributor to the overall global burden of disease. Traditionally, outdoor PM2.5 has been characterized using mass concentrations which treat all particles as equally harmful. Oxidative potential (OP) (per µg) and oxidative burden (OB) (per m3) are complementary metrics that estimate the ability of PM2.5 to cause oxidative stress, which is an important mechanism in air pollution health effects. Here, we provide the first national estimates of spatial variations in multiple measures (glutathione, ascorbate, and dithiothreitol depletion) of annual median outdoor PM2.5 OB across Canada. To do this, we combined a large database of ground-level OB measurements collected monthly prospectively across Canada for 2 years (2016-2018) with PM2.5 components estimated using a chemical transport model (GEOS-Chem) and satellite aerosol observations. Our predicted ground-level OB values of all three methods were consistent with ground-level observations (cross-validation R2 = 0.63-0.74). We found that forested regions and urban areas had the highest OB, predicted primarily by black carbon and organic carbon from wildfires and transportation sources. Importantly, the dominant components associated with OB were different than those contributing to PM2.5 mass concentrations (secondary inorganic aerosol); thus, OB metrics may better indicate harmful components and sources on health than the bulk PM2.5 mass, reinforcing that OB estimates can complement the existing PM2.5 data in future national-level epidemiological studies.