Environmental Health Long-term exposure to iron and copper in fine particulate air pollution and their combined impact on reactive oxygen species concentration in lung fluid: a population-based cohort study of cardiovascular disease incidence and mortality in Toronto, Canada Zilong Zhang, 1,2 Scott Weichenthal, 3,4 Jeffrey C Kwong, 1,2,5,6 Richard T Burnett, 7 Marianne Hatzopoulou, 8 Michael Jerrett, 9 Aaron van Donkelaar, 10,11 Li Bai, 2 Randall V Martin, 10,11,12 Ray Copes, 1,5 Hong Lu, 2 Pascale Lakey, 13 Manabu Shiraiwa, 13 and Hong Chen 1,2,5,7 * 1 Public Health Ontario, Toronto, ON, Canada, 2 ICES, Toronto, ON, Canada, 3 Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada, 4 Air Health Science Division, Health Canada, Ottawa, ON, Canada, 5 Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada, 6 Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada, 7 Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada, 8 Department of Civil and Mineral Engineering, University of Toronto, Toronto, ON, Canada, 9 School of Public Health, University of California, Los Angeles, CA, USA, 10 Department of Physics and Atmospheric Science, Dalhousie University, Halifax, NS, Canada, 11 Department of Energy, Environmental and Chemical Engineering, Washington University in St. Louis, St. Louis, MO, USA, 12 Harvard-Smithsonian Centre for Astrophysics, Cambridge, MA, USA and 13 Department of Chemistry, University of California Irvine, Irvine, CA, USA *Correspondence author. Population Studies Division, Environmental Health Science and Research Bureau, Health Canada, 101 Tunney’s Pasture Driveway, Tunney’s Pasture, A/L 0201A, Ottawa, ON K1A 0K9, Canada. E-mail: hong.chen@ canada.ca Received 13 February 2020; Editorial decision 11 October 2020; Accepted 26 October 2020 Abstract Background: Exposure to fine particulate (PM 2.5 ) air pollution is associated with in- creased cardiovascular disease (CVD), but less is known about its specific components, such as metals originating from non-tailpipe emissions. We investigated the associations of long-term exposure to metal components [iron (Fe) and copper (Cu)] in PM 2.5 with CVD incidence. Methods: We conducted a population-based cohort study in Toronto, Canada. Exposures to Fe and Cu in PM 2.5 and their combined impact on the concentration of reac- tive oxygen species (ROS) in lung fluid were estimated using land use regression V C The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association 589 IEA International Epidemiological Association International Journal of Epidemiology, 2021, 589–601 doi: 10.1093/ije/dyaa230 Advance Access Publication Date: 25 December 2020 Original article Downloaded from https://academic.oup.com/ije/article/50/2/589/6048185 by guest on 13 June 2022