ENVIRONMENTAL DETERMINANTS OF CHILDHOOD ASTHMA

The objective of this proposal is to investigate the relationships between multiple variables: cord blood IgE concentration, family history, intensity of early allergen exposure, passive cigarette smoke exposure, allergic sensitivity, bronchial hyperresponsiveness, and asthma, in children 6 to 7 years of age. The cohort of children to be studied were initially selected prenatally from families enrolled in a large HMO. Previous research has been directed toward the 141 children, from the cohort of 797 children, who were born with cord blood IgE concentrations of greater than or equal to 0.56 IU/mL. These children were thought to be at higher risk for allergic disease and were followed monthly until 2 years, then every other month until 4 years of age. Those felt to be at lower risk of allergy (IgE < 0.56 IU/ml) have been followed yearly. For this proposal, we plan to use the entire cohort of 797 children. At 5 and 6 years of age the families of the children will be contacted for telephone interviews and brief telephone contacts will be made at 4.5 and 5.5 years. As soon as possible after 6 years of age all children will be invited to undergo a clinical evaluation to determine if the child has current asthma. The evaluation will include: a review of the family allergic history, a standardized medical history, physical examination, allergen skin testing, in vitro testing for total and allergen specific IgE, urine analysis for cotinine, pulmonary function testing (FVC, FEV1, PEFR, and FEF25-75%), and methacholine challenge. The information from the clinical evaluation will be combined with previously obtained data including: measurements of allergen (mites, Der f l, Der p l; cat, Fel d l; ragweed Amb a l; and grass, Lol p l) concentrations in bedroom air and dust samples, cord blood IgE concentrations, family histories, health histories, housing records, and urinary cotinine measurements to answer the following questions. 1) What is the prevalence of diagnosed and undiagnosed asthma and of bronchial hyperresponsiveness in this cohort of children? 2) What is the relationship between asthma and bronchial responsiveness in this cohort of children? 3) Do cord blood IgE concentration, intensity of allergen exposure in infancy, family allergic history, month of birth, or degree of passive cigarette smoke exposure significantly contribute to the risk of current asthma in 6 year old children? 4) Do cord blood IgE concentration, intensity of allergen exposure in infancy, family allergic history, month of birth, or degree of passive cigarette smoke exposure significantly contribute to the risk of bronchial hyperresponsiveness or the risk of allergic sensitivity in children? 5) How much do urinary cotinine concentrations vary in children over a 4 year period and how well do reports of cigarette smoke exposure correlate with continine measurements? 6) To what degree do in home allergen concentrations vary over 4 years and what factors influence the degree of allergen variation? 7) To what degree do allergen measurements from longitudinally collected air and dust samples correlate? The strengths of this proposal are the importance of asthma as a cause of morbidity in children, the prospective and comprehensive nature of the study design, and the high probability that significant new information will be obtained about variables influencing the development of asthma in children.