Allergic asthma is the most common chronic disease of childhood in the United States. The role of exposure to allergens in asthma development is poorly understood. Our preliminary data suggest that while some aeroallergens may be risk factors, other allergens or their animal sources may be protective against asthma and allergy when encountered at the right dose, early in life. Immune mechanisms for early life allergen effects on later asthma development are uncertain. The established asthmatic response to allergens and other stimuli involves a complex interaction of T lymphocytes, B lymphocytes, and antigen-presenting cells, with the production of classic Th2 cytokines (e.g. interleukin (IL)-4, IL-13) and IgE, but also with production of non-Th2 cytokines such as IL-6 and TNF-alpha. We propose to extend our prospective longitudinal study of children of asthmatic/allergic parents to examine environmental influences on asthma and immune development, following our birth cohort into puberty, a period of significant transition when female asthma rates catch up with male rates. We hypothesize that by 12 years of age, certain early childhood home allergen exposures (cat) will decrease, while other exposures (cockroach) will increase risk of wheeze/asthma, eczema, and allergy. School-aged allergen exposures will increase airway symptoms in sensitized children. Secondly, allergen effects will be independent of other factors than may decrease (endotoxin, day care) or increase asthma or allergy risk (e.g., socioeconomic status, family history, smoking, body-mass index, stress, and for girls, early menarche). Thirdly, we hypothesize that asthma, eczema and hay fever will result from both IgE/Th2 and non-IgE/Th2 mediated mechanisms, as demonstrated in their associations with total IgE, allergen-specific IgE; IgG and IgG4 to cat measured at age 11. Finally, in a subset of 100 11 year old children with active asthma, eczema, or hay fever and 100 with no history of these syndromes, antigen (Der f 1, Fel d 1, Bla g 2) and LPS-stimulated lymphocyte production oflL-4, I1-13, IL-10, IL-6, TNF-alpha, and IFN-gamma, will also be measured. Understanding the evolution of the asthmatic immune response to allergens is an important key to developing better environmental or pharmacologic controls to either prevent or switch off the tendency to allergy and asthma in early life, before it results in chronic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI035786-15
Application #
7437367
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Plaut, Marshall
Project Start
1994-06-01
Project End
2009-07-31
Budget Start
2008-05-01
Budget End
2009-07-31
Support Year
15
Fiscal Year
2008
Total Cost
$693,069
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Hanson, Blake; Zhou, Yanjiao; Bautista, Eddy J et al. (2016) Characterization of the bacterial and fungal microbiome in indoor dust and outdoor air samples: a pilot study. Environ Sci Process Impacts 18:713-24
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Sordillo, Joanne E; Kelly, Roxanne; Bunyavanich, Supinda et al. (2015) Genome-wide expression profiles identify potential targets for gene-environment interactions in asthma severity. J Allergy Clin Immunol 136:885-92.e2
Tse, Sze Man; Coull, Brent A; Sordillo, Joanne E et al. (2015) Gender- and age-specific risk factors for wheeze from birth through adolescence. Pediatr Pulmonol 50:955-62
Bunyavanich, Supinda; Rifas-Shiman, Sheryl L; Platts-Mills, Thomas A et al. (2014) Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children. J Allergy Clin Immunol 133:1373-82
Bunyavanich, Supinda; Rifas-Shiman, Sheryl L; Platts-Mills, Thomas A E et al. (2014) Peanut allergy prevalence among school-age children in a US cohort not selected for any disease. J Allergy Clin Immunol 134:753-5
Behbod, B; Sordillo, J E; Hoffman, E B et al. (2013) Wheeze in infancy: protection associated with yeasts in house dust contrasts with increased risk associated with yeasts in indoor air and other fungal taxa. Allergy 68:1410-8
Cook, Andrea J; Gold, Diane R; Li, Yi (2013) Spatial Cluster Detection for Longitudinal Outcomes using Administrative Regions. Commun Stat Theory Methods 42:2105-2117
Tse, Sze Man; Gold, Diane R; Sordillo, Joanne E et al. (2013) Diagnostic accuracy of the bronchodilator response in children. J Allergy Clin Immunol 132:554-559.e5

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