Diesel, Allergens and Gene Interaction and Child Atopy

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DESCRIPTION (provided by investigator): Exposure to fine and ultra fine particles such as diesel exhaust particles (DEP) during early life may be associated with the later development of respiratory disorders. DEP may act as an irritant, an adjuvant for delivery of allergens to the airway and may potentiate an IgE mediated immune response. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort currently funded to 1) complete clinical examinations of children through age four and 2) enrich the estimates of exposure to DEP. This supplement adds a third specific aim to the parent study to determine if high exposure to DEP is associated with a diagnosis of asthma at age 7. Diagnosis of asthma in children requires objective measures, including pulmonary function testing, markers of airway inflammation (eNO), and methacholine challenge testing. To date, 758 infants from atopic families were evaluated annually from age 1, with an 88 per cent retention rate through age 3; age 4 physical exams are currently underway. Children have received annual skin prick tests for 15 aeroallergens, DNA buccal samples and yearly hair samples for assessing nicotine and cotinine levels. CCAAPS has extensive PM2.5 data that includes a network of 27 air sampling stations over 5 years. Source apportionment DEP signature methodologies and a land use regression model were used to estimate a child's early life and cumulative exposure to DEP. Two indoor home dust samples evaluated levels of allergens associated with dog, cat, cockroach, dust mite, as well as endotoxin, and beta-glucan. Quantitative estimates of DEP exposure was significantly associated with wheezing during infancy and early childhood. A gene:environment interaction was found between alleles of GSTP1 and high DEP exposure resulting in persistent wheeze at age two. Other recent findings indicate that exposure to DEP during a critical window of lung development, i.e., the first 12 months of life, is associated with a two fold increase in chronic wheezing at age 3 (aOR = 2.01 95 per cent CI 1.02 - 4.31). There also was a significant interaction with home exposure to endotoxin (aOR=4.14 95 per cent CI 1.5-11.7). This supplement will provide our first opportunity to obtain objective measures (eNO, nasal eosinophils, SPT, lung function, and MCCT) for the diagnosis of allergic diseases at age 7. With these data, we will have objective measures of asthma and will be able to make a more definitive assessment of an exposure-response relationship related to diesel and asthma. PUBLIC HEALTH RELEVANCE The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort whose purpose is to determine if children exposed to DEP early in life are at increased risk for the development of allergic disease and asthma during childhood and if this risk is modified by genetic factors. The study is currently funded to complete clinical examinations of children through age four and determine the exposure to DEP of children enrolled in the study. This supplement adds a third specific aim to the parent study to determine if high exposure to DEP is associated with a diagnosis of asthma at age 7 using objective measures including pulmonary function testing, markers of airway inflammation (eNO), and methacholine challenge testing.