Diesel, Allergens and Gene Interaction and Child Atopy

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DESCRIPTION (provided by applicant): There is strong evidence that diesel exhaust particles (DEP) can augment sensitization to aeroallergens and enhance expression of Th2 cytokines and allergy symptoms. Hence, DEP exposure early in life may increase allergic diseases in young children, and this risk may be modified by genotype. The purpose of this renewal is to elucidate the independent and/or combined contributions of DEP, aeroallergens, genetics, and other factors associated with allergic disease for children ages 1-4. This proposal is a request to finish testing the children at age 4 who have been followed prospectively from birth. We also propose to optimize the analysis of previously collected air samples for estimates of DEP. This study has thus far evaluated 758 infants from atopic families. Through age 3, we have 88% cohort retention, and of these, 87% are in complete study compliance. Infants received annual medical exams and had yearly skin prick tests (SPT) for 15 aeroallergens through age 3. We have collected DNA samples from children and parents and collected hair samples from infants to assess nicotine and cotinine. We established a network of 18 air sampling stations for PM2.5 and obtained five years of exposure estimates for DEP. To-date, through 28 publications, we have demonstrated a significant association with the independent or combined exposures to DEP, aeroallergen and tobacco smoke (ETS) and infant sensitization, allergic rhinitis and/or wheeze. These findings have been used by the U.S. Senate in support of the Diesel Emission Reduction Act of 2005. Further, we have findings impacting clinical evaluations as no other study has tested 15 aeroallergens in infancy. We found that at age 1 and 2, 18% and 36% of infants, respectively, are SPT+ to aeroallergens. Also, our results show significant gene:environment interactions. For example, infants with the IV/W genotype for GSTP1 and the highest DEP exposure (>0.5 A/g/m3) were significantly more likely to wheeze (18% vs 38%, p<0.01). Also, we showed that for African-Americans with high ETS exposure and the CT/TT genotype for IL4 C-589T, there was a ten fold increased risk of wheezing. In summary, this study has the potential for making a significant public health impact as allergic diseases are the most common chronic diseases of childhood. This research is poised to make additional innovative contributions to aid in the reduction of childhood allergic morbidity and mortality related to common environmental exposures.