2007 Progress Report: Air Pollution, Exhaled Breath Markers, and Asthma in Susceptible Children

EPA Grant Number: R831861C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R831861
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: USC Center for Children’s Environmental Health
Center Director: Gilliland, Frank D.
Title: Air Pollution, Exhaled Breath Markers, and Asthma in Susceptible Children
Investigators: Gilliland, Frank D.
Institution: University of Southern California
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Period Covered by this Report: November 1, 2006 through October 31, 2007
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Health Effects , Children's Health , Health

Objective:

In this project, we proposed to assess the following hypotheses:
Hypothesis 1 (H1): High ambient air pollution exposure is associated with chronic airway inflammation in children as indicated by elevated eNO, a marker of airway inflammation and oxidative/nitrosative stress.
Hypothesis 2 (H2): Children's susceptibility to airway inflammation and oxidative/nitrosative stress from ambient air pollution varies by NOS1, NOS2 and NOS3, GSTM1, GSTP1, NQO1, and HO-1 genotypes.
Hypothesis 3 (H3): Children with chronic airway inflammation as indicated by elevated eNO are at increased risk for new onset asthma.

We will assess our hypotheses by accomplishing the following specific aims:
Specific Aim 1 (SA1): Collect eNO from 3000 children in the ongoing AIR study cohort.
Specific Aim 2 (SA2): Genotype the cohort of 3000 children for functional polymorphism/haplotypes in the NOS1, NOS2 and NOS3, GSTM1, GSTP1, NQO1, and HO-1.
Specific Aim 3 (SA3): To use a multilevel design to determine the relationship between levels of eNO with short- and long-term air pollution exposures and to assess the effects of genetic variation in NOS1, 2, and 3 on these relationships using data collected in SA1, SA2 and air pollution exposure estimates from the ongoing cohort study.
Specific Aim 4 (SA4): To determine the risk for new onset asthma in children with high levels of eNO using data collected in SA1 and in the ongoing prospective cohort study of incident asthma.

Progress Summary:

In this period, we have developed new online protocols for field collection, tested methods, and trained field staff. We have completed fieldwork for enrolling subjects in the study and collecting eNO. We are beginning analysis of the data. Buccal cells for DNA were collected, processed and stored in the Molecular Biology Core. We developed NOS assays and have conducted genotyping. We also continue to follow the cohort for asthma status and exposure variables.

We have found that online eNO measured in the field is strongly correlates with offline eNO measurements (R2=.94). The technical adjustment variable contributed a small amount of additional information to explaining the differences in online and offline eNO. In analyses using air pollution metrics, we found that PM2.5 was strongly associated with eNO. NO and CO were also associated at hours to s day lag period.

Exhaled NO (eNO) has the potential for use in understanding asthma etiology, for identifying high-risk children and for use as a marker of response in intervention studies. This program of innovative research builds on the results from studies in the initial five years of the Children’s Environmental Health Center, the population resource of a large ongoing prospective cohort study of the determinants of childhood asthma incidence and an extensive cutting edge air pollution exposure assessment program to efficiently fill key research and public health needs.

Future Activities:

We plan to continue to analyzing the eNO data, complete analysis of genotyping data, and continue developing and using exposure metrics using distributed lag models. We plan to submit a manuscript on the descriptive analyses of eNO and genetic associations in this large population-based sample and the methods validation study.


Journal Articles on this Report : 9 Displayed | Download in RIS Format

Other subproject views: All 141 publications 91 publications in selected types All 90 journal articles
Other center views: All 195 publications 127 publications in selected types All 126 journal articles
Type Citation Sub Project Document Sources
Journal Article Gauderman WJ, Vora H, McConnell R, Berhane K, Gilliland F, Thomas D, Lurmann F, Avol E, Kunzli N, Jerrett M, Peters J. Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study. Lancet 2007;369(9561):571-577. R831861 (2005)
R831861 (Final)
R831861C001 (2007)
R831861C001 (Final)
R831861C002 (Final)
R831861C003 (2007)
R831861C003 (Final)
R827352 (Final)
R827352C007 (Final)
  • Abstract from PubMed
  • Full-text: Lancet-Full Text PDF
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  • Abstract: Lancet-Abstract & Full Text HTML
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  • Journal Article Gauderman WJ, Murcray C, Gilliland F, Conti DV. Testing association between disease and multiple SNPs in a candidate gene. Genetic Epidemiology 2007;31(5):383-395. R831861 (Final)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
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  • Abstract: Wiley - Abstract
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  • Journal Article Gilliland FD, Li YF, Gong Jr. H, Diaz-Sanchez D. Glutathione s-transferases M1 and P1 prevent aggravation of allergic responses by secondhand smoke. American Journal of Respiratory and Critical Care Medicine 2006;174(12):1335-1341. R831861 (2006)
    R831861 (Final)
    R831861C001 (Final)
    R831861C002 (2006)
    R831861C002 (2007)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
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  • Full-text: AJRCCM-Full Text HTML
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  • Abstract: AJRCCM-Abstract
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  • Other: AJRCCM-Full Text PDF
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  • Journal Article Gilliland FD, Islam T, Berhane K, Gauderman WJ, McConnell R, Avol E, Peters JM. Regular smoking and asthma incidence in adolescents. American Journal of Respiratory and Critical Care Medicine 2006;174(10):1094-1100. R831861 (Final)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
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  • Abstract from PubMed
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  • Full-text: ATS Journals - Full Text HTML
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  • Abstract: ATS Journals - Abstract
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  • Other: ATS Journals - Full Text PDF
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  • Journal Article Islam T, Gauderman WJ, Berhane K, McConnell R, Avol E, Peters JM, Gilliland FD. Relationship between air pollution, lung function and asthma in adolescents. Thorax 2007;62(11):957-963. R831861 (Final)
    R831861C001 (2007)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
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  • Full-text: Thorax - Full Text HTML
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  • Abstract: Thorax - Abstract
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  • Other: Thorax - Full Text PDF
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  • Journal Article Kunzli N, Avol E, Wu J, Gauderman WJ, Rappaport E, Millstein J, Bennion J, McConnell R, Gilliland FD, Berhane K, Lurmann F, Winer A, Peters JM. Health effects of the 2003 Southern California wildfires on children. American Journal of Respiratory and Critical Care Medicine 2006;174(11):1221-1228. R831861C003 (2007)
  • Full-text from PubMed
  • Abstract from PubMed
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  • Full-text: ATS Journal - Full Text HTML
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  • Abstract: ATS Journal - Abstract
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  • Other: ATS Journal - Full Text PDF
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  • Journal Article McConnell R, Berhane K, Molitor J, Gilliland F, Kunzli N, Thorne PS, Thomas D, Gauderman WJ, Avol E, Lurmann F, Rappaport E, Jerrett M, Peters JM. Dog ownership enhances symptomatic responses to air pollution in children with asthma. Environmental Health Perspectives 2006;114(12):1910-1915. R831861 (2005)
    R831861 (Final)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
    R826708 (Final)
    R827352 (Final)
    R827352C007 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article McConnell R, Berhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, Gauderman J, Avol E, Thomas D, Peters J. Traffic, susceptibility, and childhood asthma. Environmental Health Perspectives 2006;114(5):766-772. R831861 (2004)
    R831861 (2005)
    R831861 (2006)
    R831861 (Final)
    R831861C001 (2006)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2006)
    R831861C003 (2007)
    R831861C003 (Final)
    R826708 (Final)
    R827352 (Final)
    R827352C007 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Journal Article Salam MT, Gauderman WJ, McConnell R, Lin PC, Gilliland FD. Transforming growth factor-β1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma. American Journal of Respiratory and Critical Care Medicine 2007;176(12):1192-1199. R831861 (Final)
    R831861C001 (2007)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2007)
    R831861C003 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ATS Journals - Full Text HTML
    Exit
  • Abstract: ATS Journals - Abstract
    Exit
  • Other: ATS Journals - Full Text PDF
    Exit
  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Children's Health, Risk Assessment, asthma, community-based intervention, airway disease, respiratory problems, Human Health Risk Assessment, susceptibility, childhood respiratory disease, children's environmental health, outreach and education

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2006 Progress Report
  • 2008
  • 2009
  • Final Report

  • Main Center Abstract and Reports:

    R831861    USC Center for Children’s Environmental Health

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R831861C001 Urban Air Pollution and Persistent Early Life Asthma
    R831861C002 Pollution-Enhanced Allergic Inflammation and Phase II Enzymes
    R831861C003 Air Pollution, Exhaled Breath Markers, and Asthma in Susceptible Children