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Background: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function., Methods: Fifty-three healthy non-smoking volunteers (mean age 28 years, twenty-eight females) were exposed to coarse (2.5-10 μm, mean 213 μg/m 3 ), fine (0.15-2.5 μm, 238 μg/m 3 ), and/or ultrafine concentrated ambient PM (<0.3 μm, 136 μg/m 3 ). Exposures lasted 130 min, separated by ≥2 weeks. Metal concentrations and OP (measured by ascorbate and glutathione depletion in synthetic airway fluid) in PM were analyzed. Blood and urine samples were collected pre-exposure, and 1-h and 21-h post exposure for assessment of biomarkers. We used mixed-regression models to analyze associations adjusting for PM size and mass concentration., Results: Results for metals were expressed as change (%) from daily pre-exposure biomarker levels after exposure to a metal at a level equivalent to the mean concentration. Exposure to various metals (silver, aluminum, barium, copper, iron, potassium, lithium, nickel, tin, and/or vanadium) was significantly associated with increased levels of various blood or urinary biomarkers. For example, the blood inflammatory marker vascular endothelia growth factor (VEGF) increased 5.3% (95% confidence interval: 0.3%, 10.2%) 1-h post exposure to nickel; the traumatic brain injury marker ubiquitin C-terminal hydrolase L1 (UCHL1) increased 11% (1.2%, 21%) and 14% (0.3%, 29%) 1-h and 21-h post exposure to barium, respectively; and the systemic stress marker cortisol increased 1.5% (0%, 2.9%) and 1.5% (0.5%, 2.8%) 1-h and 21-h post exposure to silver, respectively. Urinary DNA oxidation marker 8‑hydroxy‑deoxy‑guanosine increased 14% (6.4%, 21%) 1-h post exposure to copper; urinary neural marker vanillylmandelic acid increased 29% (3%, 54%) 1-h post exposure to aluminum; and urinary cortisol increased 88% (0.9%, 176%) 1-h post exposure to vanadium. Results for OP were expressed as change (%) from daily pre-exposure biomarker levels after exposure to ascorbate-related OP at a level equivalent to the mean concentration, or for exposure to glutathione-related OP at a level above the limit of detection. Exposure to ascorbate- or glutathione-related OP was significantly associated with increased inflammatory and neural biomarkers including interleukin-6, VEGF, UCHL1, and S100 calcium-binding protein B in blood, and malondialdehyde and 8-hydroxy-deoxy-guanosine in urine. For example, UCHL1 increased 9.4% (1.8%, 17%) in blood 21-h post exposure to ascorbate-related OP, while urinary malondialdehyde increased 19% (3.6%, 35%) and 8-hydroxy-deoxy-guanosine increased 24% (2.9%, 48%) 21-h post exposure to ascorbate- and glutathione-related OP, respectively., Conclusion: Our results from this exploratory study suggest that metal constituents and OP in ambient PM may influence biomarker levels associated with systemic inflammation, oxidative stress, perturbations of neural function, and systemic physiological stress., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear., Objectives: We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles., Methods: Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10μm, mean 213μg/m 3 ) and fine (0.15-2.5μm, mean 238μg/m 3 ) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6nm, range 47.0-69.8nm), mean (136μg/m 3 ) and filtered medical air. Exposures lasted 130min, separated by ≥2weeks, and the biological constituents endotoxin and β-1,3-d-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post-exposure to determine neural biomarker levels. Mixed-model regressions assessed associations between exposures and changes in biomarker levels., Results: Results were expressed as percent change from daily pre-exposure biomarker levels. Exposure to coarse CAP was significantly associated with increased urinary levels of the stress-related biomarkers vanillylmandelic acid (VMA) and cortisol when compared with exposure to filtered medical air [20% (95% confidence interval: 1.0%, 38%) and 64% (0.2%, 127%), respectively] 21hours post-exposure. However exposure to coarse CAP was significantly associated with decreases in blood cortisol [-26.0% (-42.4%, -9.6%) and -22.4% (-43.7%, -1.1%) at 1h and 21h post-exposure, respectively]. Biological molecules present in coarse CAP were significantly associated with blood biomarkers indicative of blood brain barrier integrity. Endotoxin content was significantly associated with increased blood ubiquitin C-terminal hydrolase L1 [UCHL1, 11% (5.3%, 16%) per ln(ng/m 3 +1)] 1-hour post-exposure, while β-1,3-d-glucan was significantly associated with increased blood S100B [6.3% (3.2%, 9.4%) per ln(ng/m 3 +1)], as well as UCHL1 [3.1% (0.4%, 5.9%) per ln(ng/m 3 +1)], one-hour post-exposure. Fine CAP was marginally associated with increased blood UCHL1 when compared with exposure to filtered medical air [17.7% (-1.7%, 37.2%), p=0.07] 21hours post-exposure. Ultrafine CAP was not significantly associated with changes in any blood and urinary neural biomarkers examined., Conclusion: Ambient coarse particulate matter and its biological constituents may influence neural biomarker levels that reflect perturbations of blood-brain barrier integrity and systemic stress response., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Background: Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers., Objectives: We examined changes of blood and urinary biomarkers following exposures to three particle sizes., Methods: Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5-10 μm; mean, 213 μg/m3) and fine (0.15-2.5 μm; mean, 238 μg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences., Results: One hour postexposure, for every 100-μg/m3 increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs., Conclusions: Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress.