title: Influence of exposure to coarse, fine and ultrafine urban particulate matter and their biological constituents on neural biomarkers in a randomized controlled crossover study.
abstract: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear.
  
  
  
  We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles.
  
  
  
  Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10μm, mean 213μg/m3) and fine (0.15-2.5μm, mean 238μg/m3) 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/m3) 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 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/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] 21hours post-exposure. Ultrafine CAP was not significantly associated with changes in any blood and urinary neural biomarkers examined.
  
  
  
  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.
authors.affiliation: Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada. Electronic address: ling.liu@hc-sc.gc.ca.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR), Toronto, Ontario, Canada.
authors.forename: Bruce
authors.initials: B
authors.lastname: Urch
authors.affiliation: Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Szyszkowicz
authors.affiliation: Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Speck
authors.affiliation: Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Leingartner
authors.affiliation: Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Robin
authors.initials: R
authors.lastname: Shutt
authors.affiliation: Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pelletier
authors.affiliation: The Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.affiliation: Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Scott
authors.affiliation: Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR), Toronto, Ontario, Canada; Environment and Climate Change Canada, Toronto, Ontario, Canada.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Brook
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.affiliation: Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Southern Ontario Centre for Atmospheric Aerosol Research (SOCAAR), Toronto, Ontario, Canada; Divisions of Occupational Medicine and Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Frances S
authors.initials: FS
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000032:analysis; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D001812:Blood-Brain Barrier; D018592:Cross-Over Studies; D004781:Environmental Exposure; D005260:Female; D005374:Filtration; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario; D052638:Particulate Matter / Q000633:toxicity*; D011509:Proteoglycans; D012424:Rural Population; D043222:Ubiquitin Thiolesterase / Q000097:blood / Q000652:urine; D055815:Young Adult; D047071:beta-Glucans / Q000032:analysis*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D011509:Proteoglycans; C482860:UCHL1 protein, human; D047071:beta-Glucans; C010770:polysaccharide-K; D043222:Ubiquitin Thiolesterase
keywords: Air pollution; Endotoxin; Neural biomarker; Particulate matter; Randomized controlled crossover trial; β-1,3-d-glucan