Diesel, Allergens and Gene Interaction and Child Atopy

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DESCRIPTION (provided by applicant): Allergic disorders affect over 40 million children, resulting in two million missed school days and costing society more than 10 billion/year. Atopy, defined as immediate hypersensitivity to specific allergens, is the strongest risk factor for child-onset asthma. The reported increasing incidence of atopic respiratory disorders is exaggerated in urban children living in westernized countries. There is intriguing scientific evidence demonstrating that diesel exhaust particles (DEP), a constituent of truck exhaust, promote expression of Th2 cytokines and production of IgE antibodies. The concern is that these exposures enhance clinical expression of IgE mediated respiratory disorders. Hence, children residing near interstate highways are at potentially high risk for exposures to truck emissions and resultant atopic respiratory disorders. In the Cincinnati metropolitan region, three interstate corridors intersect creating one of the busiest U.S. north/south and east/west commercial truck routes converging on a population of 1.9 million. The proposed investigation will follow two groups of children from birth through early childhood. The first group are children living within 400 m of interstate highways. This group will be matched by birth date, race and income to a second group living beyond 1 km. There are two study purposes. The first is to measure DEP exposure levels and to determine if children with higher levels of exposure are at an increased risk for atopy and atopic respiratory disorders. The second is to determine if these effects are magnified in a genetically at risk subpopulation. The proposed study is a prospective cohort and nested case control design. The cohort of newborns will be evaluated prospectively for positive skin prick tests (SPT), allergic rhinitis and asthma. Residential exposures to DEP and aeroallergens also will be characterized longitudinally.The children who develop positive SPT will be matched by race and gender to controls having negative but the same number of SPT. The case control study will evaluate potential susceptiblity as measured by cytokine polymorphisms and to determine if exposure to DEP promotes the phenotypic expression of atopy and atopic respiratory disorders. This study design is optimum for determining if young children exposed to DEP have enhanced sensitization to aeroallergens and for dissecting gene-environment interactions. Results of this study may ultimately result in finding a preventable cause of atopic disorders in children.