title: Endotoxin and β-1,3-d-Glucan in Concentrated Ambient Particles Induce Rapid Increase in Blood Pressure in Controlled Human Exposures.
abstract: Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and β-1,3-d-Glucan-two major biological PM components-and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and β-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and β-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in β-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and β-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects.
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.). jiazhong@mail.harvard.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Bruce
authors.initials: B
authors.lastname: Urch
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Mary
authors.initials: M
authors.lastname: Speck
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Behrooz
authors.initials: B
authors.lastname: Behbod
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Heike
authors.initials: H
authors.lastname: Gibson
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Frances
authors.initials: F
authors.lastname: Silverman
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Murray A
authors.initials: MA
authors.lastname: Mittleman
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: From the Department of Environmental Health (J.Z., P.K., B.B., H.G., A.A.B., D.R.G.), Department of Biostatistics (B.A.C.), and Department of Epidemiology (M.A.M.), Harvard T.H. Chan School of Public Health, Boston, MA; Division of Occupational & Environmental Health, Dalla Lana School of Public Health (J.S., F.S.), Department of Medicine (B.U., J.S., F.S.), and Divisions of Occupational and Respiratory Medicine, Department of Medicine (F.S.), University of Toronto, Toronto, Ontario, Canada; Department of Occupational and Environmental Health, University of Iowa (P.S.T.); Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada (L.L.); Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI (R.D.B.); Li Ka Shing Knowledge Institute (F.S.), St Michael's Hospital (M.S., J.S., F.S.), Toronto, Ontario, Canada; Southern Ontario Center for Atmospheric Aerosol Research, Toronto, Ontario, Canada (F.S.); and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.R.G.).
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants; D001794:Blood Pressure / Q000187:drug effects*; D001795:Blood Pressure Determination; D018592:Cross-Over Studies; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000008:administration & dosage*; D011509:Proteoglycans; D016037:Single-Blind Method; D055815:Young Adult; D047071:beta-Glucans / Q000008:administration & dosage*
chemical_list: D000393:Air Pollutants; D004731:Endotoxins; D052638:Particulate Matter; D011509:Proteoglycans; D047071:beta-Glucans; C010770:polysaccharide-K
keywords: air pollution; blood pressure; endotoxin; vascular endothelial growth factor; β-1,3-d-Glucan