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

Article excerpt

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 ukrafine 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-a 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 [micro] in aerodynamic diameter ([PM.sub.25],[PM.sub.0.25-2.5],[PM.sub.2.5-10])] and hourly elemental and black carbon (EC-BC), estimated primary and secondary organic carbon ([OC.sub.pri], SOC), particle number (PN), carbon monoxide (CO), and nitrogen oxides-nitrogen dioxide ([NO.sub.x]-[NO.sub.2]). We analyzed the relation of biomarkers to exposures with mixed effects models adjusted for potential confounders.

RESULTS: Primary combustion markers (EC-BC, [OC.sub.pri], CO, [NO.sub.x]-[NO.sub.2]), but not SOC, were positively associated with inflammatory biomarkers and inversely associated with erythrocyte antioxidant enzymes (n = 578). PN and [PM.sub.0.25] were more strongly associated with biomarkers than [PM.sub.0.25-2.5] Associations for all exposures were stronger during cooler periods when only [OC.sub.prj], PN, and [NO.sub.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.

KEY WORDS: cytokines, enzymes, epidemiology, longitudinal data analysis, oxidative stress. Environ Health Perspect 117:1232-1238 (2009). doi:10.1289/ehp.0800194 available via[Online 29 April 2009]


Ambient mass con centra rions of particulate matter (PM) air pollution < 2.5 [micro]m ([PM.sub.2.5]) and < 10 [micro]m ([PM.sub.10]) 'n aerodynamic diameter have been associated with hospital admissions and mortality due to cardiovascular causes in time series studies (Pope and Dockery 2006). Mechanisms involving oxidative stress and inflammation have been proposed to explain these associations (Mills et al. 2007) (Figure 1). In addition, a growing toxicology literature suggests that ultrafine particles (UFP), < 0.1 [micro]m in diameter, may have greater potential to induce oxidative stress and inflammation than larger particles that dominate [PM.sub.2.5] and [PM.sub.10] mass (Ntziachristos et al. 2007). This is likely because compared with larger particles, UFP have a higher airway deposition efficiency, magnitudes higher particle number (PN) concentration and surface area, and higher concentrations of organic components shown to induce oxidative stress responses (Li et al. 2003). The ability of UFP to translocate systemically from pulmonary sites makes them particularly relevant to the cardiovascular effects of inhaled PM (Elder and Oberdorster 2006).

We aimed to improve the characterization of PM exposure in order to yield clues to potentially important pollutant sources and causal component mixtures not otherwise evident with ambient [PM.sub.2.5] and [PM.sub.10] mass, which are regulated by the U.S. Environmental Protection Agency (Delfino et al. 2005) (Figure 1). For example, traffic (a common exposure source of redox active PM) increases spatial variability of UFP (Sioutas et al. …