title: Oxidative burden of fine particulate air pollution and risk of cause-specific mortality in the Canadian Census Health and Environment Cohort (CanCHEC).
abstract: BACKGROUND
  Fine particulate air pollution (PM2.5) is known to contribute to cardiorespiratory mortality but it is not clear how PM2.5 oxidative burden (i.e. the ability of PM2.5 to cause oxidative stress) may influence long-term mortality risk.
  
  
  METHODS
  We examined the relationship between PM2.5 oxidative burden and cause-specific mortality in Ontario, Canada. Integrated PM2.5 samples were collected from 30 provincial monitoring sites between 2012 and 2013. The oxidative potential (% depletion/µg) of regional PM2.5 was measured as the ability of filter extracts to deplete antioxidants (glutathione and ascorbate) in a synthetic respiratory tract lining fluid. PM2.5oxidative burden was calculated as the product of PM2.5 mass concentrations and regional estimates of oxidative potential. In total, this study included 193,300 people who completed the Canadian long-form census in 1991 and who lived within 5km of a site where oxidative potential was measured. Deaths occurring between 1991 and 2009 were identified through record linkages and Cox proportional hazard models were used to estimate hazard ratios (and 95% confidence intervals) for interquartile changes in exposure adjusting for individual-level covariates and indirect-adjustment for smoking and obesity.
  
  
  RESULTS
  Glutathione-related oxidative burden was associated with cause-specific mortality. For lung cancer specifically, this metric was associated with a 12% (95% CI: 5.0-19) increased risk of mortality whereas a 5.0% (95% CI: 0.1, 10) increase was observed for PM2.5. Indirect adjustment for smoking and obesity decreased the lung cancer hazard ratio for glutathione-related oxidative burden but it remained significantly elevated (HR=1.07, 95% CI: 1.005, 1.146). Ascorbate-related oxidative burden was not associated with mortality.
  
  
  CONCLUSIONS
  Our findings suggest that glutathione-related oxidative burden may be more strongly associated with lung cancer mortality than PM2.5 mass concentrations.
authors.affiliation: Health Canada, Ottawa, Ontario, Canada. Electronic address: scott.weichenthal@hc-sc.gc.ca.
authors.forename: Scott
authors.initials: S
authors.lastname: Weichenthal
authors.affiliation: University of New Brunswick, Fredericton, New Brunswick, Canada.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Crouse
authors.affiliation: Statistics Canada, Ottawa, Ontario, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Pinault
authors.affiliation: University of Massachusetts, Amherst, MA, USA.
authors.forename: Krystal
authors.initials: K
authors.lastname: Godri-Pollitt
authors.affiliation: Health Canada, Ottawa, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Lavigne
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Evans
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: van Donkelaar
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada; Harvard-Smithsonian Center for Astrophysics, Cambridge, MA, USA.
authors.forename: Randall V
authors.initials: RV
authors.lastname: Martin
authors.affiliation: Health Canada, Ottawa, Ontario, Canada.
authors.forename: Rick T
authors.initials: RT
authors.lastname: Burnett
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality*; D015331:Cohort Studies; D004781:Environmental Exposure; D004782:Environmental Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D018384:Oxidative Stress; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D016016:Proportional Hazards Models; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000401:mortality*; D012307:Risk Factors
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Lung cancer; Mortality; Oxidative potential; PM(2.5)