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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050681-05
Application #
7084397
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Minnicozzi, Michael
Project Start
2002-07-15
Project End
2008-08-31
Budget Start
2006-05-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$600,174
Indirect Cost
Name
Henry Ford Health System
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Wegienka, Ganesa; Sitarik, Alexandra; Bassirpour, Gillian et al. (2018) The associations between eczema and food and inhalant allergen-specific IgE vary between black and white children. J Allergy Clin Immunol Pract 6:292-294.e2
Cassidy-Bushrow, A E; Burmeister, C; Havstad, S et al. (2018) Prenatal antimicrobial use and early-childhood body mass index. Int J Obes (Lond) 42:1-7
Sitarik, Alexandra R; Bobbitt, Kevin R; Havstad, Suzanne L et al. (2017) Breast Milk Transforming Growth Factor ? Is Associated With Neonatal Gut Microbial Composition. J Pediatr Gastroenterol Nutr 65:e60-e67
Havstad, Suzanne; Sitarik, Alexandra R; Johnson, Christine Cole et al. (2017) Allergic sensitization in American children of Middle Eastern ethnicity at age 2. Ann Allergy Asthma Immunol 119:464-466
Cassidy-Bushrow, Andrea E; Sitarik, Alexandra R; Havstad, Suzanne et al. (2017) Burden of higher lead exposure in African-Americans starts in utero and persists into childhood. Environ Int 108:221-227
Wegienka, G; Havstad, S; Kim, H et al. (2017) Subgroup differences in the associations between dog exposure during the first year of life and early life allergic outcomes. Clin Exp Allergy 47:97-105
Sitarik, Alexandra R; Bobbitt, Kevin R; Havstad, Suzanne L et al. (2017) Breast Milk TGF? is Associated with Neonatal Gut Microbial Composition. J Pediatr Gastroenterol Nutr :
Levin, Albert M; Sitarik, Alexandra R; Havstad, Suzanne L et al. (2016) Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity. Sci Rep 6:31775
Cassidy-Bushrow, A E; Sitarik, A; Levin, A M et al. (2016) Maternal group B Streptococcus and the infant gut microbiota. J Dev Orig Health Dis 7:45-53
Cassidy-Bushrow, Andrea E; Wegienka, Ganesa; Havstad, Suzanne et al. (2016) Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years. Ethn Dis 26:61-8

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