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. 2008 Jul;116(7):898-906.
doi: 10.1289/ehp.11189.

Circulating biomarkers of inflammation, antioxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coronary artery disease

Ralph J Delfino  1 , Norbert Staimer, Thomas Tjoa, Andrea Polidori, Mohammad Arhami, Daniel L Gillen, Micheal T Kleinman, Nosratola D Vaziri, John Longhurst, Frank Zaldivar, Constantinos Sioutas
Affiliations

Circulating biomarkers of inflammation, antioxidant activity, and platelet activation are associated with primary combustion aerosols in subjects with coronary artery disease

Ralph J Delfino et al. Environ Health Perspect. 2008 Jul.

Abstract

Background: Biomarkers of systemic inflammation have been associated with risk of cardiovascular morbidity and mortality.

Objectives: We aimed to clarify associations of particulate matter (PM) air pollution with systemic inflammation using models based on size-fractionated PM mass and markers of primary and secondary aerosols.

Methods: We followed a panel of 29 nonsmoking elderly subjects with a history of coronary artery disease (CAD) living in retirement communities in the Los Angeles, California, air basin. Blood plasma biomarkers were measured weekly over 12 weeks and included C-reactive protein (CRP), fibrinogen, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor-II (sTNF-RII), interleukin-6 (IL-6) and its soluble receptor (IL-6sR), fibrin D-dimer, soluble platelet selectin (sP-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), intracellular adhesion molecule-1 (sICAM-1), and myeloperoxidase (MPO). To assess changes in antioxidant capacity, we assayed erythrocyte lysates for glutathione peroxidase-1 (GPx-1) and copper-zinc superoxide dismutase (Cu,Zn-SOD) activities. We measured indoor and outdoor home daily size-fractionated PM mass, and hourly pollutant gases, total particle number (PN), fine PM elemental carbon (EC) and organic carbon (OC), estimated secondary organic aerosol (SOA) and primary OC (OCpri) from total OC, and black carbon (BC). We analyzed data with mixed models controlling for temperature and excluding weeks with infections.

Results: We found significant positive associations for CRP, IL-6, sTNF-RII, and sP-selectin with outdoor and/or indoor concentrations of quasi-ultrafine PM < or = 0.25 microm in diameter, EC, OCpri, BC, PN, carbon monoxide, and nitrogen dioxide from the current-day and multiday averages. We found consistent positive but largely nonsignificant coefficients for TNF-alpha, sVCAM-1, and sICAM-1, but not fibrinogen, IL-6sR, or D-dimer. We found inverse associations for erythrocyte Cu,Zn-SOD with these pollutants and other PM size fractions (0.25-2.5 and 2.5-10 microm). Inverse associations of GPx-1 and MPO with pollutants were largely nonsignificant. Indoor associations were often stronger for estimated indoor EC, OCpri, and PN of outdoor origin than for uncharacterized indoor measurements. There was no evidence for positive associations with SOA.

Conclusions: Results suggest that traffic emission sources of OCpri and quasi-ultrafine particles lead to increased systemic inflammation and platelet activation and decreased antioxidant enzyme activity in elderly people with CAD.

Keywords: acute-phase proteins; cytokines; enzymes; epidemiology; longitudinal data analysis; oxidative stress; panel study; particulate air pollution.

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Figures

Figure 1
Figure 1
Relationships of biomarkers of inflammation to outdoor air pollutants (adjusted coefficient and 95% CI). (A) CRP (ng/mL). (B) IL-6 (pg/mL). (C) sTNF-RII (pg/mL). Expected change in the biomarker corresponds to an interquartile range change in the air pollutant (Table 3). Abbreviations: ave, average; Est coef, estimated coefficient.
Figure 2
Figure 2
Relationships of biomarkers of inflammation to indoor air pollutants (adjusted coefficient and 95% CI). (A) CRP (ng/mL). (B) IL-6 (pg/mL). (C) sTNF-RII (pg/mL). Abbreviations: ave, average; Est coef, estimated coefficient; o_o, indoor concentrations of outdoor origin. Expected change in the biomarker corresponds to an interquartile range change in the air pollutant (Table 3).
Figure 3
Figure 3
Relationship of sP-selectin to outdoor and indoor air pollutants (adjusted coefficient and 95% CI). (A) Outdoor air pollutants. (B) Indoor air pollutants. Abbreviations: ave, average; Est coef, estimated coefficient; o_o, indoor concentrations of outdoor origin. Expected change in sP-selectin (ng/mL) corresponds to an interquartile range change in the air pollutant (Table 3).
Figure 4
Figure 4
Relationship of Cu,Zn-SOD to outdoor and indoor air pollutants (adjusted coefficient and 95% CI). (A) Outdoor air pollutants. (B) Indoor air pollutants. o_o, indoor concentrations of outdoor origin; Est Coef, estimated coefficient. Expected change in Cu,Zn-SOD (U/g Hb) corresponds to an interquartile range change in the air pollutant (Table 3).
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