2005 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, 2004 through October 31, 2005
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:

The objectives of this research project are 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 exhaled nitric oxide (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 nitric oxide synthase 1 (NOS1), NOS2, and NOS3, and 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 3,000 children in the ongoing AIR study cohort.

Specific Aim 2 (SA2):  Genotype the cohort of 3,000 children for functional polymorphism/haplotypes in the NOS1, NOS2, and NOS3, and GSTM1, GSTP1, NQO1, and HO-1.

To assess H1 and H2:

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 NOS 1, NOS2, and NOS3 on these relationships using data collected in SA1, SA2, and air pollution exposure estimates from the ongoing cohort study.


To assess H3: 

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 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 nitric oxide synthase assays and are beginning to extract DNA in preparation for genotyping.  We also continue to follow the cohort for asthma status and exposure variables.  Figure 1 shows the preliminary distribution of eNO in the cohort (incomplete sample size because of data issues).

Significance

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.  The program of innovative research proposed in this application builds on the results from studies in the initial 5 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 fill key research and public health needs efficiently.

Figure 1.  Preliminary Distribution of eNO in the Cohort (Incomplete Sample Size)

Figure 1.  Preliminary Distribution of eNO in the Cohort (Incomplete Sample Size)

Future Activities:

We plan to continue analyzing the eNO data, complete DNA extraction and begin genotyping the cohort for the proposed genes, and continue developing exposure metrics as the exposure measurements become available.  We plan to investigate the use of GIS methods to examine these data.  We also plan to submit a manuscript on the determinants of eNO in this large population-based sample as our first paper.


Journal Articles on this Report : 1 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, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, Kuenzli N, Lurmann F, Rappaport E, Margolis H, Bates D, Peters J. The effect of air pollution on lung development from 10 to 18 years of age. New England Journal of Medicine 2004;351(11):1057-1067. R831861 (2004)
R831861 (2005)
R831861 (Final)
R831861C001 (Final)
R831861C002 (Final)
R831861C003 (2005)
R831861C003 (Final)
  • Abstract from PubMed
  • Full-text: New England Journal of Medicine-Full Text HTML
    Exit
  • Abstract: New England Journal of Medicine-Abstract
    Exit
  • Other: New England Journal of Medicine-Full Text PDF
    Exit
  • Supplemental Keywords:

    asthma, children, susceptibility, community, children’s health, health effects, risk assessment, airway disease, allergen, asthma, childhood respiratory disease, children’s environmental health, community-based intervention, outreach and education, respiratory problems,, 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

    Relevant Websites:

    http://www.usc.edu/schools/medicine/research/centers_programs/cehc/ Exit
    http://www.usc.edu/schools/medicine/departments/preventive_medicine/divisions/occupational/occ_environmental/cehc/index.html Exit

    Progress and Final Reports:

    Original Abstract
  • 2004 Progress Report
  • 2006 Progress Report
  • 2007 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