2001 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: Southern California Particle Center and Supersite
Center Director: Froines, John R.
Title: Respiratory Disease and Prevention Center
Investigators: Gong, Henry , Gilliland, Frank D.
Current Investigators: Gong, Henry , Gilliland, Frank D. , Jones, Craig , McConnell, Rob Scot
Institution: Rancho Los Amigos Medical Center , University of California - Los Angeles
EPA Project Officer: Louie, Nica
Project Period: January 1, 1998 through January 1, 2002
Project Period Covered by this Report: January 1, 2000 through January 1, 2001
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 , Health Effects , Health

Objective:

This research project builds on an ongoing prospective cohort study of children in 12 California communities to assess the hypotheses that:  (1) dietary intake of fruits, vegetables, and antioxidants; and (2) polymorphisms in genes involved in lung defenses (GSTM1, GSTT1, GSTP1, MPO, TNF-α) 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 (particulate matter; PM10 and PM2.5).

The primary specific objectives of this research project are to:  (1) determine whether functional lung growth is decreased and respiratory illnesses are increased by low dietary intake of fruits and vegetables, low dietary intake of antioxidant vitamins (C, E), homozygosity for the common (A) allele in the promoter region of MPO (polymorphic allele has a G to A at position -463 of the MPO gene), and presence of one TNF2 allele; and (2) determine whether susceptibility to slow functional lung growth, respiratory symptoms, and respiratory illness from exposure to O3, NO2, PM10, and PM2.5 is increased by low dietary intake of fruits and vegetables, low dietary intake of antioxidant vitamins (C, E), high intake of dietary fat with a high polyunsaturated fat to total fat ratio, homozygosity for the null allele at the GSTM1 and GSTT1 loci or the presence of one A105G allele at the GSTP1 locus, homozygosity for the common (A) allele in promoter region of MPO (polymorphic allele has a G to A at position -463 of the MPO gene), and presence of one TNF2 allele.

Progress Summary:

Buccal Cell Collection

We have collected by mail and stored 419 buccal samples for the DNA resource.  One challenge for the study was recruitment of subjects in the longitudinal study who have moved outside of the school catchment areas or may choose not to participate in this study.  We have not been able to trace 152 of 1,066 participants selected.  Of those contacted, about 85 percent have agreed to participate in the study.  We expected at least 50 percent of those we contact to volunteer for the genotyping study.  We have continued to exceed this response rate.

We have collected updated health questionnaires from 766 former Cardiovascular Health Study (CHS) participants by mail and telephone interview.  The questionnaires have been edited and an entry system developed.  We are beginning to examine the data and will link it with the CHS database to allow longitudinal analyses.

Diet Assessment

In Year 3, we have collected a total of 2,072 food frequency questionnaires (FFQs) from active participants during lung function testing.  We collected diet questionnaires for active cohort members (groups C and D) during the first 6 months of 2000.  Questionnaires have been edited and sent to Harvard University for scanning.  We are in the process of assembling analytic data sets for longitudinal analyses and are examining the nutrient data from 2000 for outliers using age-specific criteria based on multiples of basal metabolic rate.  We also have collected a total of 390 diet questionnaires by mail from participants who no longer reside in the study areas.

We have conducted cross-sectional analyses for the first FFQs and lung function.  A manuscript on magnesium intake and lung function showing deficits with low intake, especially for children with asthma, has been accepted for publication.  A second paper on the relationship between vitamins A, C, and E, and lung function is in preparation, which follows an abstract presentation at the American Thoracic Society meeting. We found that low intake of antioxidant vitamins is associated with lower lung function. We also found little evidence supporting a relationship between any component of fat intake and lung function.  Several other manuscripts on asthma risk factors and determinants of lung function are under review or in preparation.

Genotyping

A Taqman was purchased to increase the throughput of our assays.  We have revised our assay methods to meet the requirements of the Taqman technology.  We have assessed and finalized DNA extraction procedures for the buccal cell specimens and developed primers for Taqman-based assays for GSTMI, GSTT1, GSTP1, TNF-α, and MPO.  We are in the process of completing and verifying more than 3,000 genotypes for GSTM1, GSTP1, and GSTT1.  We have conducted 1,000 TNF-α genotypes.  We have conducted preliminary analyses but are awaiting final genotyping data for further analyses.

Significance

The ongoing prospective cohort study of children residing in a highly polluted environment presents a unique opportunity to identify modifiable factors that influence lung health in a culturally diverse population.  Because the traits of interest are complex and clearly involve a number of physiologic processes, we anticipate that the magnitude of main effects and gene-environment interactions for the candidate genes and diet may be modest for an individual; however, each may make an important contribution to the population attributable risk.  Our studies of genes with high population attributable risk, but with modest individual effects, will have detailed exposure assessment, careful end-point measurement and classification, and include a large enough sample size to obtain precise and accurate estimates of modest effects.  The possibility of gene-gene interactions also will be considered, especially for metabolic genes with overlapping substrate specificity.  This study already has an extensive database and infrastructure that will facilitate the successful completion of the specific aims. Findings of the study have the potential to influence public health policy and improve the health of children.

Future Activities:

We will collect a fourth diet questionnaire for all active cohort members (group D) again in the first 6 months of 2002.  The ongoing longitudinal study will collect pulmonary function data, medical history, residential history and characteristics, and time activity patterns from group D through Year 10 of followup.  We plan to collect buccal cells from a remaining subset of group D at the schools in the fall of 2001 and spring of 2002.  We will continue to collect buccal cells from at least 125 participants during 2002 from groups A, B, and C who graduated from the CHS.  We plan to complete genotyping in Years 4 and 5 of the funding period.  We will continue to analyze the cross-sectional data using diet information and genotype data.  Preliminary longitudinal analyses will be conducted in Year 4 of the grant period, and final longitudinal analyses will be conducted in the final 6 months of the grant period.


Journal Articles on this Report : 5 Displayed | Download in RIS Format

Other subproject views: All 10 publications 10 publications in selected types All 10 journal articles
Other center views: All 92 publications 63 publications in selected types All 61 journal articles
Type Citation Sub Project Document Sources
Journal Article Berhane K, McConnell R, Gilliland F, Islam T, Gauderman WJ, Avol E, London SJ, Rappaport E, Margolis HG, Peters JM. Sex-specific effects of asthma on pulmonary function in children. American Journal of Respiratory and Critical Care Medicine 2000;162(5):1723-1730. R826708 (2000)
R826708 (2001)
R826708 (2002)
R826708 (Final)
R826708C001 (2001)
R826708C003 (2001)
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  • Journal Article Gauderman WJ, McConnell R, Gilliland F, London S, Thomas D, Avol E, Vora H, Berhane K, Rappaport EB, Lurmann F, Margolis HG, Peters J. Association between air pollution and lung function growth in southern California children. American Journal of Respiratory and Critical Care Medicine 2000;162(4 Pt 1):1383-1390. R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R826708C001 (2000)
    R826708C001 (2001)
    R826708C003 (2001)
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  • Journal Article Gilliland FD, Li YF, Peters JM. Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. American Journal of Respiratory and Critical Care Medicine 2001;163(2):429-436. R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R826708C003 (2001)
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  • Journal Article Gilliland FD, Berhane K, Rappaport EB, Thomas DC, Avol E, Gauderman WJ, London SJ, Margolis HG, McConnell R, Islam KT, Peters JM. The effects of ambient air pollution on school absenteeism due to respiratory illnesses. Epidemiology 2001;12(1):43-54. R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R826708C003 (2001)
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  • Journal Article Li Y-F, Gilliland FD, Berhane K, McConnell R, Gauderman WJ, Rappaport EB, Peters JM. Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma. American Journal of Respiratory and Critical Care Medicine 2000;162(6):2097-2104. R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R826708C001 (2001)
    R826708C003 (2001)
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  • Supplemental Keywords:

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

    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
  • 1998
  • 1999
  • 2000 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R826708    Southern California Particle Center and Supersite

    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