Ambient air pollution is well accepted as a cause of asthma exacerbations, but its role in the etiology of new onset asthma is less clear. Evidence for an etiologic role of ambient air pollutants is emerging from epidemiologic studies; however, the ecologic patterns of increasing asthma prevalence concurrent with decreasing levels of some pollutants have raised questions about the validity of these associations. A better understanding of the biological processes that mediate the effects of ambient air pollution on asthma occurrence is likely to contribute to answering these questions. Chronic oxidative/nitrosative stress and airway inflammation are probably critical processes in asthma etiology and these inter-related processes may mediate the increased asthma risk from air pollution. In this application, we propose to use exhaled NO (eNO), to study the role of inflammation and oxidative/nitrosative stress in the pathobiology of new onset asthma, with a focus on ambient air pollution and genetic susceptibility. We choose ambient pollutants based on potential contribution to oxidative/nitrosative stress (O3; particulates (PM10 and PM2.5 and their chemical constituents, particle counts, NOx (NO and NO2), acid vapors; and fresh tailpipe emissions). The primary hypotheses to be assessed in the proposed program of research are: 1) children with high ambient air pollution exposures have chronic airway inflammation as indicated by elevated eNO. 2) susceptibility to airway inflammation and oxidative/nitrosative stress from ambient air pollution varies by NOS1, NOS2. NOS3. GSTM1. GSTP1. NQO1, and HO-1 haplotypes and functional variants, and 3) children with chronic airway inflammation as indicated by elevated eNO are at increased risk for new onset asthma. To test these hypotheses, the proposed study builds on the population resource of the Asthma Incidence Risk (AIR) study, an ongoing prospective cohort study of the determinants of new onset asthma in 6000 children in 13 southern California communities, and an extensive program of ambient air pollution exposure characterization in these communities. In this application, we propose to measure eNO using off-line techniques and to genotype 3000 children from the AIR cohort. A number of resources will enhance the proposed study, including the Children's Environmental Health Center, the Molecular Biology Core of Southern California Environmental Health Sciences Center, and expertise from the Southern California Particle Center and Supersite. The findings from the proposed research program is likely to contribute to resolving uncertainties about the effects of air pollution on asthma risk, provide new tools for identifying children at highest risk for asthma and aid in asthma prevention efforts. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL076647-03
Application #
7254062
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Banks-Schlegel, Susan P
Project Start
2005-08-15
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$693,500
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Zhang, Yue; Salam, Muhammad T; Berhane, Kiros et al. (2017) Genetic and epigenetic susceptibility of airway inflammation to PM2.5 in school children: new insights from quantile regression. Environ Health 16:88
Zhang, Yue; Berhane, Kiros (2016) Dynamic Latent Trait Models with Mixed Hidden Markov Structure for Mixed Longitudinal Outcomes. J Appl Stat 43:704-720
Eckel, Sandrah P; Zhang, Zilu; Habre, Rima et al. (2016) Traffic-related air pollution and alveolar nitric oxide in southern California children. Eur Respir J 47:1348-56
Salam, Muhammad T; Lin, Pi-Chu; Eckel, Sandrah P et al. (2015) Inducible Nitric Oxide Synthase Promoter Haplotypes and Residential Traffic-Related Air Pollution Jointly Influence Exhaled Nitric Oxide Level in Children. PLoS One 10:e0145363
Salam, Muhammad T; Avoundjian, Tigran; Knight, Wendy M et al. (2015) Genetic Ancestry and Asthma and Rhinitis Occurrence in Hispanic Children: Findings from the Southern California Children's Health Study. PLoS One 10:e0135384
Eckel, Sandrah P; Linn, William S; Salam, Muhammad T et al. (2015) Spirometry effects on conventional and multiple flow exhaled nitric oxide in children. J Asthma 52:198-204
Zhang, Yue; Berhane, Kiros; Eckel, Sandrah P et al. (2015) Determinants of Children's Exhaled Nitric Oxide: New Insights from Quantile Regression. PLoS One 10:e0130505
Urman, Robert; McConnell, Rob; Islam, Talat et al. (2014) Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants. Thorax 69:540-7
Bunyavanich, Supinda; Schadt, Eric E; Himes, Blanca E et al. (2014) Integrated genome-wide association, coexpression network, and expression single nucleotide polymorphism analysis identifies novel pathway in allergic rhinitis. BMC Med Genomics 7:48

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