DIET, IMMUNE MODULATION, AND ASTHMA IN EARLY LIFE

Brigham And Women'S Hospital, Boston MA

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Abstract

DESCRIPTION Asthma is the most common chronic disease of childhood in the developed world, affecting about 10 million U.S. children under the age of sixteen. Asthma prevalence in Western industrialized countries is increasing at an alarming rate, and this increase is coincident with an increase in type I hypersensitivity (allergy). Eighty percent of childhood asthmatics exhibit hypersensitivity to indoor aeroallergens. Maternal diet represents an important exposure that has significant potential to modify immune function and, hence, the development of allergy. To study the evolution of the asthmatic immune response, focusing on the cellular response to allergens and foods, this application proposes a collaborative study involving pulmonary and dietary epidemiologists (Drs. Weiss, Colditz, and Gold), experts in lipid biochemistry (Dr. Sacks) and immunologists specializing in the role of T- and B-cells in the asthmatic response (Drs. Finn and Perkins). The application proposes to utilize a prospective longitudinal cohort study of children of asthmatic mothers to examine the role of maternal dietary fat intake (N-3 polyunsaturated fat) in the development of (1) nonspecific and specific cellular immune responses by age 2-3; (2) asthma/wheeze, atopic dermatitis, food allergy, and allergic rhinitis by age 3. In a subset of 50 five year old children with asthmatic mothers, 25 with high and 25 with low N-3 fatty acid intake during pregnancy, studies will assess lymphocyte proliferation and cytokine production (IL-4, IL-5, and interferon-gamma [IFN-gamma]) to nonspecific (PHA) and representative specific antigenic stimulation: beta-lactoglobin (food), cockroach (Bla g2) and dust mite (Der fI) (indoor allergen). Additional potentially influential host and environmental factors to be examined include: parental asthma history, maternal age, perinatal history, acute lower respiratory illness history, day care, environmental tobacco smoke, birthweight, head circumference, sex, and race. The application proposes to test the following hypotheses: 1. At birth, maternal dietary N-3 fatty acid levels assessed in the second and third trimester of pregnancy with a semiquantitative food frequency questionnaire will be correlated with N-3 fatty acid levels in cord blood. 2. At birth, infants with high cord blood levels of N-3 fatty acids will have reduced lymphocyte proliferative responses to cockroach, dust mite (indoor allergen), and beta-lactoglobin and reduced levels of inflammatory cytokines (IL-4, IL-5) and increased levels of interferon-gamma. 3. High cord blood levels of N-3 fatty acids and reduced lymphoproliferative responses to cockroach, dust mite and beta-lactoglobin will independently predict decreased development of allergic disease (asthma/wheeze, atopic dermatitis, food allergy, and allergic rhinitis) at age 3.