Research Grants/Fellowships/SBIR

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)
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text |  Recipients Lists
Research Category: Health Effects , Children's Health , Health


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), nitric oxide synthase 2 (NOS2), and nitric oxide synthase 3 (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 NOS1, 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/Accomplishments:  The delay in funding precluded collecting eNO samples during the 2003-2004 school year.  We will begin collection from 3,000 children in September of the 2004-2005 school year.  We have begun to develop and implement the genotyping assays for NOS1, NOS2, and NOS3.  Buccal cell DNA will be collected in the 2004-2005 school year.


eNO has the potential for use in understanding asthma etiology, for identification of 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.

Publications and Presentations:

Publications have been submitted on this subproject: View all 141 publications for this subprojectView all 193 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 91 journal articles for this subprojectView all 127 journal articles for this center

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

Progress and Final Reports:

2004 Progress Report
2005 Progress Report
2006 Progress Report
2007 Progress Report
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