Early Environmental Hygiene and Pediatric Atopy

Henry Ford Health System, Detroit MI

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The overall objective of this research application is to relate early life environmental factors associated with microbacterial exposure to cytokine profile phenotypes and biological markers associated with risk for pediatric allergy and asthma. These markers are serum total IgE and serum allergen-specific IgE. We will measure exposure variables theorized to reflect the "Hygiene Hypothesis" which suggests that a less "sterile" environment during the first months of life acts through the gut to result in an immune profile dominated by type 1 immunity (Th1 phenotype) that is protective against clinical atopic conditions. The general hypothesis to be tested is that markers of a child's exposure to bacteria in our culture, such as sustained contact with animals, older siblings, and daycare, will be associated with the early development of a Th1 phenotype, lower serum total IgE and an absence of serum specific IgE to common allergens. Factors that alter the gut's flora, such as the early and frequent use of antibiotics, will be associated with the maintenance of a Th2 phenotype. We believe these associations may be modified by early onset clinical viral infections and breastfeeding patterns, and confounded by variables such as race, gender, and household allergen level, and parental history including positive allergen-specific IgE to pets. Capitalizing on our extensive experience with an earlier birth cohort, we will establish a larger, multi-ethnic and socio-economically diverse new birth cohort. During the first year of life, we will collect extensive exposure (including household dust endotoxin and allergen levels), clinical, and biomarker data, specifically measurement of intracellular cytokine production (interleukin 4 and interferon y) by T-helper lymphocytes as indicators of either a Th1 or Th2 profile. Follow up of these children will culminate at two years of age with a blood draw for measurement of allergen-specific IgE as a marker of allergic sensitization. While this project focuses on early outcomes, our long-term goal will be to evaluate these factors and their relationship to clinical allergy and persistent asthma in these children as they grow older. Further, working with Dr. F. Martinez, we will use the established repository of biospecimens to develop molecular epidemiologic studies of genetic-environmental risk factors.