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，柴油废气微粒(DEP)可以增强对空气过敏原的敏感性，并增强Th2细胞因子的表达和过敏症状。因此，生命早期接触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改变而改变。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、空气变应原、遗传学和其他因素的独立和/或联合作用。这项提案是要求完成对4岁儿童的测试，这些儿童从出生起就被前瞻性地跟踪。我们还建议优化以前收集的空气样本的分析，以估计DEP。到目前为止，这项研究已经评估了758名来自特应症家庭的婴儿。到3岁，我们有88%的队列保留率，其中87%完全符合研究要求。婴儿每年接受体检，并在3岁前每年进行15种空气过敏原的皮肤点刺试验(SPT)。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的五年暴露估计。到目前为止，通过28份出版物，我们已经证明了独立或联合暴露于DEP、空气过敏原和烟草烟雾(ETS)与婴儿致敏、过敏性鼻炎和/或喘息之间存在显著关联。这些调查结果已被美国参议院用来支持2005年的柴油减排法案。此外，我们有影响临床评估的发现，因为没有其他研究在婴儿时期测试过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呈SPT+。此外，我们的结果还显示了显著的基因-环境交互作用。例如，GSTP1的IV/W基因型和最高的DEP暴露(&gt；0.5A/g/m~3)的婴儿更容易喘息(18%比38%，p&lt；0.01)。此外，我们还发现，对于接触高ETS且携带IL4C-589T CT/TT基因的非裔美国人来说，发生喘息的风险增加了10倍。总而言之，这项研究有可能对公共卫生产生重大影响，因为过敏性疾病是儿童最常见的慢性疾病。这项研究准备做出更多的创新贡献，以帮助减少与常见环境暴露有关的儿童过敏发病率和死亡率。

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.