Diesel, Allergens and Gene Interaction and Child Atopy

描述（由申请人提供）：过敏性疾病影响超过4000万人 儿童，造成200万个缺课日，社会成本增加 超过100亿/年。特应性，定义为对特定 过敏原是儿童哮喘发病的最大危险因素。所报告的 在城市地区，特应性呼吸系统疾病的发病率增加被夸大， 生活在西方国家的孩子们。有一个有趣的科学 有证据表明，柴油机排气颗粒（DEP），一种成分， 促进Th 2细胞因子的表达和IgE的产生 抗体的令人担忧的是，这些暴露增强了 IgE介导的呼吸系统疾病。因此，住在州际公路附近的孩子 高速公路暴露于卡车排放物的潜在高风险， 从而导致特应性呼吸障碍。 在辛辛那提大都市区，三条州际走廊相交 创造了美国南北和东西最繁忙的商用卡车之一， 路线汇聚了190万人口。拟议的调查 将跟随两组儿童从出生到幼儿期。的 第一组是居住在州际公路400米范围内的儿童。这群 根据出生日期、种族和收入， 1公里有两个研究目的。首先是测量DEP暴露水平 并确定暴露水平较高的儿童是否会增加 特应性和特应性呼吸系统疾病的风险。第二，确定是否 这些影响在遗传风险亚群中被放大。的 本研究采用前瞻性队列和巢式病例对照设计。的 将前瞻性评价新生儿队列的皮肤点刺阳性 过敏性鼻炎和哮喘。住宅暴露于DEP和 空气性过敏原也将被纵向表征。 发生阳性SPT的受试者将按种族和性别与对照组相匹配， 阴性，但SPT数量相同。病例对照研究将评估 通过细胞因子多态性测量的潜在易感性，并确定 如果暴露于DEP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人是否 暴露于DEP的儿童对空气过敏原的敏感性增强， 剖析基因与环境的相互作用这项研究的结果可能最终 从而找到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.