Grantee Research Project Results

2002 Progress Report: Respiratory Disease and Prevention Center

EPA Grant Number: R826708C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R826708
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Respiratory Disease and Prevention Center
Investigators: Gong, Henry , Gilliland, Frank D.
Current Investigators: Gong, Henry , Gilliland, Frank D. , McConnell, Rob Scot , Jones, Craig
Institution: Rancho Los Amigos Medical Center , University of California - Los Angeles
EPA Project Officer: Hahn, Intaek
Project Period: January 1, 1998 through January 1, 2002
Project Period Covered by this Report: January 1, 2001 through January 1, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Children's Health , Human Health

Objective:

This study builds on an ongoing prospective cohort study of children in 12 California communities to assess the hypotheses that 1) dietary intake of fruits, vegetables, antioxidants; and 2) polymorphisms in genes involved in lung defenses affect children's susceptibility for slow lung function growth and increased occurrence of respiratory illnesses from chronic exposure to ozone (O3) nitrogen dioxide (NO2), and respirable particles (PM10 and PM2.5). In the study, we plan to genotype approximately 3000 children at five loci.

The primary specific aims are:
1) To determine whether functional lung growth is decreased and respiratory illnesses are increased by: a) low dietary intake of fruits and vegetables and antioxidant vitamins; b) GSTM1, GSTT1, GSTP1, c) MPO and TNF2 allele; 2) To determine whether susceptibility to 1) slow functional lung growth, 2) respiratory symptoms, and 3) respiratory illness from exposure to O3, NO2, PM10 and PM2.5 is increased by: a) low dietary intake of fruits, vegetables, and antioxidant vitamins; b) high intake of polyunsaturated fat; c) GSTM1, GSTT1, GSTP1, d) MPO and TNF2 allele.

Progress Summary:

Studies and Results

The cohort of children and adolescents who have participated in the Children's Health Study (CHS) form the base population for the longitudinal study of childhood determinants of susceptibility. We are collecting updated medical histories, dietary information, buccal cells for genotyping and verifying medical history of asthma. Tracing subjects has proved to be a major challenge requiring substantial effort. Based on the findings that in utero exposure to maternal smoking is associated with decreased lung function especially in children with asthma and is also associated with increased risk of early onset asthma, Investigators have continued validating medical histories of asthma by contacting parents for telephone interviews and have completed a counter-matched prevalence case-control study nested in the cohort. As of 5/24/2002, they have interviewed 194 parents or guardians for the incident asthma cases and a set of controls. They are continuing to collect buccal cells by mail. They have found that extraction of the DNA from cells using a commercial kit (Purgene) provides stable DNA specimens for cleaner genotyping results. They have genotyped 3200 specimens at GSTM1, T1, and P1 and TNFa using Taqman assays and have conducted several analyses. They have been delayed in genotyping MPO because of difficulties in designing the probe for the wild type allele. They found that polymorphisms of GSTM1 and GSTP1 are associated with early onset asthma (before age five years) and severity of wheezing. They have observed an additive interaction between GSTP1 and GSTM1 for wheezing. They found that polymorphisms of GSTM1 and GSTP1 are associated with early onset asthma (before age five years) and severity of wheezing in those exposed to in utero smoking. A manuscript has been accepted for publication. They have observed a 3-way interaction between in utero exposure, GSTP1 and GSTM1 in the occurrence of wheezing.

Investigators have conducted preliminary analyses of the risk for newly diagnosed asthma among CHS participants with available genotyping data. They found a significant protective effect for the GSTP1 Val allele. A manuscript is in preparation. They have observed a two-fold increased risk of asthma among participants who begin to smoke cigarettes as well as who became obese. Manuscripts are in preparation.

They have observed a statistically significant effect of GSTM1 and PI on lung function growth, especially measures of small airway flows. They have examined the effects of GSTM1, PI and Tl on respiratory illness-related school absenteeism. In preliminary analyses of our 1996 school absenteeism cohort, we found that GSTP1, but not GSTM1 or TI, was associated with rates of respiratory related absences. A manuscript reporting these findings is in press.

They are currently examining the effect of the TNF -308 polymorphism on lung function growth, asthma and wheezing occurrence, and absences. They are continuing to examine the effects o diet on lung function and asthma outcomes. A manuscript is in preparation to report the findings relating Vitamin C and A to lung function level in children. They are planning to examine gene - air pollution and diet air pollution interactions in detail in the next year.

Future Activities:

Investigators plan to analyze the nested case-control study of early life events and asthma and the medical records validation study. We will begin genotyping subjects for MPO and continue TNFA and the GSTS. They will continue to collect buccal cells, health update and diet questionnaires for cohort members. The ongoing longitudinal study will collect exposure data. They plan additional analyses of the dietary data in the next year and continued examination of the effects of tobacco smoke and ambient air pollution on children's respiratory health.

Journal Articles:

No journal articles submitted with this report: View all 10 publications for this subproject

Supplemental Keywords:

Allergens, Asthma, Biochemistry, Children's Health, Human Health Risk Assessment, air pollutants, airway disease, airway inflammation, epidemiology, human exposure, environmental tobacco smoke., RFA, Scientific Discipline, Health, Geographic Area, Health Risk Assessment, State, Risk Assessments, Disease & Cumulative Effects, Biochemistry, Children's Health, health effects, air pollutants, air toxics, infants, vulnerability, lung disease, age-related differences, airway disease, gene-environment interaction, lead, pulmonary disease, respiratory problems, second hand smoke, air pollution, children, Human Health Risk Assessment, human exposure, lung dysfunction, children's vulnerablity, genetic risk factors, disease resistance, childhood respiratory disease, exposure pathways, harmful environmental agents, indoor air, environmental health hazard, dietary exposure, environmental tobacco smoke, tobacco smoke, California (CA), dietary factors, cancer risk, disease, exposure assessment, human health risk

Relevant Websites:

The link to University of Southern California is:
https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/outlinks.centers

Progress and Final Reports:

Original Abstract

1998

1999

2000 Progress Report

Final Report

Main Center Abstract and Reports:

R826708    Great Lakes Air Center for Integrative Environmental Research

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826708C001 Asthma in Children: A Community-based Intervention Project
R826708C002 Children's Exposure to Environmental Tobacco Smoke: Changes in Allergic Response
R826708C003 Respiratory Disease and Prevention Center