Diesel, Allergens and Gene Interaction and Child Atopy

描述(申请人提供)：过敏性疾病影响4000多万人 造成200万天缺课，并使社会付出更多代价 超过100亿/年。特应性，定义为对特定疾病的即刻超敏 过敏原是儿童哮喘的最大危险因素。据报道， 城市特应性呼吸疾病发病率的增加被夸大了 生活在西化国家的儿童。有耐人寻味的科学研究 有证据表明，柴油废气颗粒物(DEP)是 汽车尾气，促进Th2细胞因子的表达和IgE的产生 抗体。令人担忧的是，这些暴露增强了临床上的 免疫球蛋白介导的呼吸系统疾病。因此，居住在州际公路附近的儿童 高速公路暴露于卡车尾气的潜在风险很高， 由此产生的特应性呼吸系统疾病。 在辛辛那提大都市区，三条州际走廊相交 创造了美国最繁忙的北/南和东/西商用卡车之一 聚集在190万人口上的路线。拟议中的调查 将跟踪两组儿童从出生到儿童早期。这个 第一组是居住在州际高速公路400米范围内的儿童。这群人 将在出生日期、种族和收入方面与生活在更远的第二个群体匹配 1公里。有两个研究目的。第一种是测量DEP暴露水平 并确定暴露水平较高的儿童是否会增加 患特应性和特应性呼吸系统疾病的风险。第二个是确定是否 这些影响在遗传风险亚群中被放大。这个 建议的研究为前瞻性队列嵌套病例对照设计。这个 将对新生儿队列中的阳性皮肤刺激性进行前瞻性评估 试验(SPT)、过敏性鼻炎和哮喘。住宅暴露于环境保护署和 空气过敏原也将被纵向表征。 发展成阳性的SPT将按种族和性别与对照相匹配， 阴性，但SPT数量相同。病例对照研究将评估 用细胞因子多态来衡量潜在的易感性，并确定 如果暴露于DEP可促进特应性和特应性的表型表达 呼吸系统疾病。这项研究设计是确定年轻的 接触DEP的儿童对空气过敏原和 剖析基因与环境的相互作用。这项研究的结果最终可能 结果找到了儿童特应性疾病的可预防原因。

DESCRIPTION (provided by applicant): Allergic disorders affect over 40 million children, resulting in two million missed school days and costing society more than 10 billion/year. Atopy, defined as immediate hypersensitivity to specific allergens, is the strongest risk factor for child-onset asthma. The reported increasing incidence of atopic respiratory disorders is exaggerated in urban children living in westernized countries. There is intriguing scientific evidence demonstrating that diesel exhaust particles (DEP), a constituent of truck exhaust, promote expression of Th2 cytokines and production of IgE antibodies. The concern is that these exposures enhance clinical expression of IgE mediated respiratory disorders. Hence, children residing near interstate highways are at potentially high risk for exposures to truck emissions and resultant atopic respiratory disorders. In the Cincinnati metropolitan region, three interstate corridors intersect creating one of the busiest U.S. north/south and east/west commercial truck routes converging on a population of 1.9 million. The proposed investigation will follow two groups of children from birth through early childhood. The first group are children living within 400 m of interstate highways. This group will be matched by birth date, race and income to a second group living beyond 1 km. There are two study purposes. The first is to measure DEP exposure levels and to determine if children with higher levels of exposure are at an increased risk for atopy and atopic respiratory disorders. The second is to determine if these effects are magnified in a genetically at risk subpopulation. The proposed study is a prospective cohort and nested case control design. The cohort of newborns will be evaluated prospectively for positive skin prick tests (SPT), allergic rhinitis and asthma. Residential exposures to DEP and aeroallergens also will be characterized longitudinally.The children who develop positive SPT will be matched by race and gender to controls having negative but the same number of SPT. The case control study will evaluate potential susceptiblity as measured by cytokine polymorphisms and to determine if exposure to DEP promotes the phenotypic expression of atopy and atopic respiratory disorders. This study design is optimum for determining if young children exposed to DEP have enhanced sensitization to aeroallergens and for dissecting gene-environment interactions. Results of this study may ultimately result in finding a preventable cause of atopic disorders in children.