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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
Title: Air Pollution, Exhaled Breath Markers, and Asthma in Susceptible Children
Investigators: Gilliland, Frank
Institution: University of Southern California
EPA Project Officer: Fields, Nigel
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)
Research Category: Children's Health , Health Effects

Description:

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 24 publications 23 publications in selected types All 23 journal articles
Other center views: All 138 publications 125 publications in selected types All 125 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. The Lancet 2007;369(9561):571-577. R831861 (2005)
R831861C001 (2007)
R831861C003 (2007)
R827352 (Final)
R827352C007 (Final)
  • Abstract from PubMed
  • Full-text: Science Direct Full Text
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  • Other: Science Direct PDF
    Exit EPA Disclaimer
  • 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. R831861C003 (2007)
    not available
    Journal Article Gilliland FD, Li YF, Gong H Jr, 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. R831861C003 (2007)
    not available
    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. R831861C003 (2007)
    not available
    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. R831861C001 (2007)
    R831861C003 (2007)
    not available
    Journal Article Künzli 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 wildfire on children. American Journal of Respiratory and Critical Care Medicine 2006;174(11):1221-1228. R831861C003 (2007)
    not available
    Journal Article McConnell R, Berhane K, Molitor J, Gilliland F, Künzli N, Thorne P, Thomas D, Gauderman J, 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)
    R831861C003 (2007)
    R827352 (Final)
    R827352C007 (Final)
  • Abstract from PubMed
  • Full-text: Environmental Health Perspectives Full Text
    Exit EPA Disclaimer
  • Other: Environmental Health Perspectives PDF
    Exit EPA Disclaimer
  • 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)
    R831861C001 (2006)
    R831861C003 (2006)
    R831861C003 (2007)
    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- 1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma. American Journal of Respiratory and Critical Care Medicine 2007;176(12):1192-1199. R831861C001 (2007)
    R831861C003 (2007)
    not available
    Supplemental Keywords:

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

    Progress and Final Reports:
    2004 Progress Report
    2005 Progress Report
    2006 Progress Report
    Original Abstract


    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

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    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.


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