Air Pollution Exposures and Circulating Biomarkers of Effect in a Susceptible Population: Clues to Potential Causal Component mixtures and mechanisms

BACKGROUND: Mechanisms involving oxidative stress and inflammation have been proposed to explain associations of ambient air pollution with cardiovascular morbidity and mortality. Experimental evidence suggests that organic components and ultrafine particles (UFP) are important. METHODS: We conducted a panel study of 60 elderly subjects with coronary artery disease living in retirement communities within the Los Angeles, California, air basin. Weekly biomarkers of inflammation included plasma interleukin-6, tumor necrosis factor-alpha soluble receptor II (sTNF-RII), soluble platelet selectin (sP-selectin), and C-reactive protein (CRP). Biomarkers of erythrocyte antioxidant activity included glutathione peroxidase-1 and superoxide dismutase. Exposures included outdoor home daily particle mass particulate matter < 0.25, 0.25-2.5, and 2.5-10 microm in aerodynamic diameter (PM(0.25), PM(0.25-2.5), PM(2.5-10)), and hourly elemental and black carbon (EC-BC), estimated primary and secondary organic carbon (OC(pri), SOC), particle number (PN), carbon monoxide (CO), and nitrogen oxides-nitrogen dioxide (NO(x)-NO(2)). We analyzed the relation of biomarkers to exposures with mixed effects models adjusted for potential confounders. RESULTS: Primary combustion markers (EC-BC, OC(pri), CO, NO(x)-NO(2)), but not SOC, were positively associated with inflammatory biomarkers and inversely associated with erythrocyte anti-oxidant enzymes (n = 578). PN and PM(0.25) were more strongly associated with biomarkers than PM(0.25-2.5). Associations for all exposures were stronger during cooler periods when only OC(pri), PN, and NO(x) were higher. We found weaker associations with statin (sTNF-RII, CRP) and clopidogrel use (sP-selectin). CONCLUSIONS: Traffic-related air pollutants are associated with increased systemic inflammation, increased platelet activation, and decreased erythrocyte antioxidant enzyme activity, which may be partly behind air pollutant-related increases in systemic inflammation. Differences in association by particle size, OC fraction, and seasonal period suggest components carried by UFP are important.