Impact/Purpose:

nbsp; 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.

Significance

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.

nbsp; 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.

Significance

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.

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 Summa