Influence of exposure to coarse, fine and ultrafine urban particulate matter and their biological constituents on neural biomarkers in a randomized controlled crossover study

摘要

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 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 (mean size 59.6 nm, range 47.0–69.8 nm), mean (136 μg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥2 weeks, 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] 21 hours 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 1 h and 21 h 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/m3 + 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/m3 + 1)], as well as UCHL1 [3.1% (0.4%, 5.9%) per ln(ng/m3 + 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] 21 hours 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. Keywords: Air pollution, Particulate matter, Endotoxin, β-1,3-d-glucan, Neural biomarker, Randomized controlled crossover trial