Factors in Childhood Lung Susceptibility to Pollution

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00233285
First received: October 3, 2005
Last updated: April 13, 2009
Last verified: April 2009
  Purpose

To investigate gene-environment interactions that may influence susceptibility to respiratory illness in children living in highly polluted areas in California.


Condition
Lung Diseases
Asthma

Study Type: Observational

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: September 1999
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Ambient air pollutants and tobacco smoke produce adverse respiratory health effects in children. Differences in susceptibility for these outcomes are likely to involve genetic variation in multiple pathophysiological pathways that modulate responses and subsequent biologic effects following exposure. The study initially investigated the hypothesis that genetic variants in oxidant stress pathways modulate the occurrence of adverse outcomes using a candidate gene approach in the Children's Health Study (CHS), a longitudinal study of children's respiratory health in 12 Southern California communities. The investigators found that variants in GSTM1 (null), GSTP1 (A105G), TNF (- 308), and ICAM-1 (241) were associated with reduced lung function growth, increased asthma occurrence, and increased respiratory illnesses. These variants also showed gene-environment and gene-gene interactions with tobacco smoke and ambient air pollutants. Their findings add to the growing body of evidence that pathways involving glutathione (GSH) play important roles in respiratory health.

DESIGN NARRATIVE:

In the initial grant period, the investigators studied the effects of ambient air pollution and tobacco smoke on children's respiratory health and the role of diet, physical activity and genetic variation on susceptibility to ambient air pollutants and completed each of the specific aims. They noted associations between genotypes studied and reduced lung function growth, increased sensitivity to in utero exposure to maternal smoking, increased the risk of asthma, and risk of respiratory-related school absences, varied by GSTM1 and GSTP1 genotype. They noted that diets low in antioxidant vitamins were associated with deficits in lung function and that low magnesium intake was associated with lung function deficits. Finally, the investigators identified haplotype structure and tag single nucleotide polymorphisms (SNPs) for selected candidate loci and employed a limited version of haplotype analysis for investigation of association of three ICAM-1 variants on childhood asthma.

The investigators will extend their candidate gene association study using existing data from the Children's Health Study (CHS), to examine the role of sequence variation in 38 genes in five glutathione (GSH) pathways including GSH production, transport, and redox cycling, electrophil and oxidation products detoxification, and nitric oxide cell signaling. The exposures of interest are ozone (O3), nitric oxide (NO2), ambient PM2.5, and tobacco smoke. The respiratory health outcomes are lung function growth, asthma, and respiratory absences. Associations of respiratory health outcomes with sequence variants in candidate genes and air pollution will be assessed using haplotypes and functional SNPs. They will test for overall association of a locus with outcomes using functional SNPs and a haplotype-based approach, and gene-gene and gene-environment interaction within and between pathways will also be examined using approaches to minimize multiple comparisons issues. Confounding by admixture will be addressed using SNP-based genome-wide control methods. Finally, hierarchical Bayesian models of these complex pathways incorporate a priori knowledge about biological relationships to efficiently examine interactions within and between pathways.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00233285

Sponsors and Collaborators
Investigators
Investigator: Frank Gilliland University of Southern California
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00233285     History of Changes
Other Study ID Numbers: 1306
Study First Received: October 3, 2005
Last Updated: April 13, 2009
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Asthma
Lung Diseases
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014