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shows the associations between endotoxin in CAPs and urinary biomarkers. Endotoxin in coarse and fine CAPs was associated with increased urinary VEGF at 1 hr postexposure. Endotoxin in coarse CAP was associated with increased 8-OHdG at 1 hr postexposure. Exposure to endotoxin in fine CAP was associated with increased urinary MDA at 1 hr and 21 hr postexposure at p-values 0.08 and 0.07, respectively. Glucan was not associated with any urinary biomarkers (see Supplemental Material, Table S2).

shows the regression results for changes in urinary biomarkers per 100-μg/m3 increase in CAP mass concentrations. Exposures to coarse and ultrafine CAPs were associated with increased urinary 8-OHdG at 1 hr postexposure, and exposure to fine CAP was associated with increased MDA at 1 hr and 21 hr postexposure, in single- and two-pollutant models. Fine CAP showed a consistent trend of association with urinary VEGF at 1 hr postexposure in single- and two-pollutant models (p-values 0.07–0.10). Adding gases in the models as a covariate moderately strengthened the associations between CAPs and urinary biomarkers by rendering smaller p-values, but the magnitude of the associations did not change markedly, suggesting that gases may have minor confounding influence over the results for CAPs. Nevertheless, not adjusting for gases might underestimate the strength of the associations. The number count variable for ultrafine CAP yielded similar regression outcomes (see Supplemental Material, Table S3).

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For the study on coarse and fine CAPs, we recruited in total 58 subjects. Eight subjects withdrew from the study, one due to high blood pressure, another due to high blood cholesterol level, and six due to time conflicts. For the ultrafine CAP study, five additional subjects were enrolled to make the total sample size of 25 subjects. In total, 55 female and male participants were enrolled. For the characteristics of the cohort, see Supplemental Material,Table S1.

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Exposure facility. Details of the coarse, fine, and ultrafine particle concentrator facility were described elsewhere (). The controlled exposures to CAPs drew air from breathing height adjacent to a downtown street in Toronto, Canada. We used the Harvard Ambient Fine and Coarse Particle Concentrators (Harvard School of Public Health) and an enclosed temperature-controlled exposure chamber for the study participants. Ambient aerosols were drawn through a size-selective inlet where particles >10 μm were removed. The fine PM concentrator delivered CAP 0.15–2.5 μm in MMAD (fine CAP), and the coarse PM concentrator delivered CAP 2.5–10 μm in MMAD (coarse CAP). Particle-free filtered ambient air (FA) was used as a control by inserting a high-efficiency particulate absorption (HEPA) filter inline downstream of the particle concentrator. For the study on coarse and fine CAPs, we enrolled 50 participants. Early in the study, we observed a pattern of similar postexposure changes in outcome measures (for example, blood pressure and blood neutrophils) for FA and CAP exposures. We hypothesized that ambient gaseous pollutants may have contributed to the FA responses. To explore this possibility, for another exposure to 41 participants, we added HEPA-filtered cylinder medical air that was particle- and ambient gas–free. The study for the coarse and fine CAPs included up to five exposures for each participant when he or she was available: two exposures to coarse CAP, and one exposure to fine CAP, HEPA-filtered ambient air, and/or filtered medical air.

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presents the associations between endotoxin in CAPs and biomarker concentrations in blood. Endotoxin in coarse CAP was significantly associated with increased VEGF at 1 hr postexposure. Endotoxin was not associated with other blood biomarkers. Glucan was not associated with any of the blood biomarkers (see Supplemental Material, Table S2).

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In this study, we hypothesized that a) a short-term exposure to concentrated ambient coarse, fine, or ultrafine PM would be associated with increased systemic inflammation, oxidative stress, and changes in mediators of vascular function in healthy individuals, detectable through biomarkers; and b) primary biological material in these particles might play a role in concentrated ambient particle (CAP)–related systemic effects.

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We used VEGF and ET-1 as biomarkers of vascular function, and found that coarse CAP and the endotoxin constituent in coarse and fine CAPs were associated with a transient increase in blood and urinary VEGF levels. VEGF regulates the mobilization of endothelial progenitor cells from bone marrow to an injured site (). Increased VEGF levels may represent an acute systemic response to endothelial injury during exposure to PM and endotoxin. Daily exposure to indoor and outdoor PM2.5 and black carbon has been associated with increased blood VEGF levels in seniors (). To our knowledge, the present study is the first to report an association between exposure to ambient PM and endotoxin and elevated urinary VEGF levels. ET-1 is an endogenous vasoconstrictor (). Elevated plasma ET-1 was found in children who were chronically exposed to air pollution in Mexico City () and in seniors on high-pollution days (). In the present study, we did not observe changes in blood ET-1. This discrepancy might be attributable to differences in the participants’ demographics and health status compared to other cited studies.

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