Diesel, Allergens and Gene Interaction and Child Atopy

柴油、过敏原和基因相互作用以及儿童特应性

基本信息

批准号：
7329269
负责人：
Grace LeMasters
金额：
$ 16.64万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-30 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7329269
关键词：
Adjuvant Admission activity Admixture Adult Affect Age Age of Onset Air Conditioning Alleles Allergens Allergic Allergic rhinitis Alternaria Antibodies Antigens Aspergillus Asthma Biological Markers Birth Birth Certificates Boston Calendar Canis familiaris Case-Control Studies Categories Causations Censuses Child Childhood Asthma Clinical Cohort Studies Country Cytokine Receptors DNA Data Date of birth Developing Countries Development Dictyoptera Diesel Exhaust Disease Dust Environmental Exposure Environmental Risk Factor Environmental air flow Exposure to Extrinsic asthma Face Family Felis catus Female Fungal Spores Gender Gene Frequency Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Genotype Heating High Prevalence Hospitals Hour Hypersensitivity skin testing IgE In Vitro Incidence Income Individual Infant Interleukin 4 Receptor Interleukin-13 Interleukin-4 Investigation Kentucky Life Link Literature Location Lung diseases Measures Mediating Methods Molds Monitor Nested Case-Control Study New York Newborn Infant Numbers Ohio Parents Particulate Particulate Matter Pattern Phenotype Pilot Projects Pollen Population Population Heterogeneity Populations at Risk Predisposition Prevalence Production Purpose Pyroglyphidae Race Rate Records Relative (related person)Relative Risks Reporting Research Design Resources Respiration Disorders Risk Risk Factors Rivers Route Rural Schools Serum Skin Smog Societies Source Spore Counts Stratification Surface System Testing Time Transportation Xenobiotics Zip Code airborne allergen atopy base case control cohort cost cytokine day design early childhood exhaust gene environment interaction gene interaction genetic association genetic linkage genetic variant grass pollen human study in vivo insight male meter metropolitan particle particle exposure pollutant postnatal programs prospective residence respiratory response size social trafficking transmission process urban area

项目摘要

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.

描述（由申请人提供）：过敏性疾病影响超过 4000 万人儿童，导致 200 万人缺课，给社会造成更多损失超过100亿/年。特应性，定义为对特定的立即超敏反应过敏原是儿童哮喘的最强危险因素。报道称城市中特应性呼吸系统疾病发病率的增加被夸大了生活在西方国家的儿童。有一个有趣的科学道理有证据表明，柴油机尾气颗粒（DEP）是卡车尾气，促进Th2细胞因子的表达和IgE的产生抗体。令人担忧的是，这些暴露会增强临床表达 IgE 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面临卡车排放的潜在高风险由此导致的特应性呼吸系统疾病。在辛辛那提都会区，三个州际走廊相交打造美国南北和东/西最繁忙的商用卡车之一多条路线汇聚了 190 万人口。拟议的调查将跟踪两组儿童从出生到幼儿期的整个过程。这第一组是居住在州际公路 400 m 以内的儿童。本组将根据出生日期、种族和收入与生活在更远地区的第二组进行匹配 1公里。学习目的有两个。第一个是测量 DEP 暴露水平并确定暴露水平较高的儿童是否处于增加的状态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人群中会被放大。这拟议的研究是一项前瞻性队列和巢式病例对照设计。这将对新生儿队列进行前瞻性皮肤点刺阳性评估测试（SPT）、过敏性鼻炎和哮喘。住宅暴露于 DEP 和空气过敏原也将被纵向表征。制定积极的 SPT 将根据种族和性别进行匹配，以控制有阴性但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潜在的易感性并确定如果接触 DEP 会促进特应性和特应性的表型表达呼吸系统疾病。该研究设计最适合确定是否年轻接触 DEP 的儿童对空气过敏原的敏感性增强，并且剖析基因与环境的相互作用。这项研究的结果可能最终结果发现儿童特应性疾病的可预防原因。