title: The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.
abstract: Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Ananya
authors.initials: A
authors.lastname: Roy
authors.affiliation: Duke University, Nicholas School of the Environment and Duke Global Health Institute, Durham, North Carolina, United States of America.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Gong
authors.affiliation: University of Southern California, Keck School of Medicine, Department of Preventive Medicine, Los Angeles, California, United States of America.
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.affiliation: Duke University, Nicholas School of the Environment and Duke Global Health Institute, Durham, North Carolina, United States of America.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Kipen
authors.affiliation: University of Rochester, School of Medicine and Dentistry, Department of Public Health Sciences. Rochester, New York, United States of America.
authors.forename: David Q
authors.initials: DQ
authors.lastname: Rich
authors.affiliation: Peking University, State Key Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, and the Center for Environment and Health, Beijing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Peking University, School of Public Health, Department of Occupational and Environmental Health and Institute of Environmental Medicine, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Peking University, State Key Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, and the Center for Environment and Health, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Peking University First Hospital, Department of Pulmonary Medicine, Beijing, China.
authors.forename: Guangfa
authors.initials: G
authors.lastname: Wang
authors.affiliation: Peking University Health Sciences Center, Department of Immunology, Beijing, China.
authors.forename: Yuedan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Peking University First Hospital, Department of Hematology, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Rutgers School of Public Health, Department of Biostatistics, Piscataway, New Jersey, United States of America.
authors.forename: Shou-En
authors.initials: SE
authors.lastname: Lu
authors.affiliation: Rutgers School of Public Health, Department of Biostatistics, Piscataway, New Jersey, United States of America.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ohman-Strickland
authors.affiliation: Rutgers School of Dentistry, Center for Pharmacogenomics and Complex Disease, Newark, New Jersey, United States of America.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Diehl
authors.affiliation: University of Southern California, Keck School of Medicine, Department of Preventive Medicine, Los Angeles, California, United States of America.
authors.forename: Sandrah P
authors.initials: SP
authors.lastname: Eckel
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects* / Q000032:analysis; D001337:Autonomic Agents / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D011014:Pneumonia / Q000139:chemically induced / Q000453:epidemiology* / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D001337:Autonomic Agents; D015415:Biomarkers