Diesel, Allergens and Gene Interaction and Child Atopy

描述（由申请人提供）：有强有力的证据表明，柴油机排气颗粒（DEP）可增强对空气过敏原的致敏作用，并增强Th 2细胞因子的表达和过敏症状。因此，在生命早期暴露于DEP可能会增加幼儿的过敏性疾病，并且这种风险可能会因基因型而改变。此次更新的目的是阐明与1-4岁儿童过敏性疾病相关的DEP、空气过敏原、遗传学和其他因素的独立和/或综合贡献。该提案要求在4岁时完成对从出生起就进行前瞻性跟踪的儿童的测试。我们还建议优化分析以前收集的空气样本估计DEP。迄今为止，这项研究评估了758名来自特应性家庭的婴儿。在3岁之前，我们有88%的队列保留率，其中87%完全符合研究要求。婴儿每年接受一次体检，并每年进行一次皮肤点刺试验（SPT），以检测15种空气过敏原，直至3岁。我们收集了儿童和父母的DNA样本，并收集了婴儿的头发样本，以评估尼古丁和可替宁。我们建立了一个由18个PM2.5空气采样站组成的网络，并获得了DEP五年的暴露估计值。迄今为止，通过28篇出版物，我们已经证明了与DEP，空气过敏原和烟草烟雾（ETS）的独立或组合暴露与婴儿致敏，过敏性鼻炎和/或喘息的显着关联。这些发现已被美国参议院用于支持2005年柴油机减排法案。此外，我们有影响临床评价的发现，因为没有其他研究在婴儿期测试了15种空气过敏原。我们发现，在1岁和2岁时，分别有18%和36%的婴儿对空气过敏原的SPT+。此外，我们的研究结果显示了显着的基因：环境相互作用。例如，具有GSTP 1 IV/W基因型和最高DEP暴露（>0.5 A/g/m3）的婴儿更容易发生喘息（18% vs 38%，p<0.01）。此外，我们还发现，对于ETS暴露水平较高且IL 4 C-589 T基因型为CT/TT的非裔美国人，其喘息风险增加了10倍。总之，这项研究有可能产生重大的公共卫生影响，因为过敏性疾病是儿童最常见的慢性疾病。这项研究准备作出额外的创新贡献，以帮助减少儿童过敏的发病率和死亡率与常见的环境暴露。

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.