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：
7497526
负责人：
Grace LeMasters
金额：
$ 70.8万
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 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7497526
关键词：
4 year old Address Adverse effects African American Age Air Pollution Alleles Allergens Allergic Allergic rhinitis Animals Appendix Area Asthma Atopic Dermatitis Autopsy Biological Markers Birth Breathing CD14 gene Canis familiaris Child Child health care Childhood Chronic Disease Cities Clinical Collection Complex Mixtures Condition Cotinine DNA Data Deposition Development Dictyoptera Diesel Exhaust Disease Disease regression Eczema Endotoxins Environment Environmental Exposure Environmental Risk Factor Evaluation Exposure to Extrinsic asthma Family Felis catus Female Figs - dietary Funding Future GSTP1 gene Gender Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Transcription Genetic Variation Genotype Glucans Glutathione S-Transferase Grant Hair Health Home environment House Dust Mite Allergens Human Hypersensitivity IL4 gene Immunity Incidence Individual Infant Inflammation Inflammatory Interleukin-13 Interleukin-4 Japanese Population Journals Knowledge Lead Letters Life Lung Lung diseases Measures Medical Medicine Methodology Metric Mexico Modeling Molds Monitor Morbidity - disease rate Nicotine Nose Numbers Onset of illness Other Genetics Outcome Oxidative Stress Parents Particulate Pathogenesis Pattern Peripheral Phenotype Policies Pollen Polymorphism Analysis Population Predisposition Principal Investigator Progress Reports Public Health Publications Purpose Pyrenes Race Reactive Oxygen Species Recording of previous events Relative (related person)Research Research Design Research Personnel Rhinitis Risk Risk Factors Role Sampling Severities Siblings Skin Surface Symptoms T-Lymphocyte Testing Time Tobacco smoke Ultrafine Universities Variant Wheezing Woman Work air sampling airborne allergen airway epithelium atopy base clinical phenotype cohort college cytochrome P-450 CYP2A6 (human)cytokine early childhood early onset environmental allergen eosinophil food allergen forging gene environment interaction gene interaction genetic analysis genetic variant glutathione S-transferase pi improved inclusion criteria infancy innovation insight land use member mortality non-smoker particle particle exposure peer postnatal programs promoter pyrene pyroglyphid research clinical testing respiratory response time interval trafficking

项目摘要

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.

描述（由申请人提供）：有强有力的证据表明柴油机尾气颗粒（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型而改变。本次更新的目的是阐明 DEP、空气过敏原、遗传学以及与 1-4 岁儿童过敏性疾病相关的其他因素的独立和/或综合作用。该提案要求对从出生起就进行前瞻性随访的 4 岁儿童完成检测。我们还建议优化之前收集的空气样本的分析，以估计 DEP。迄今为止，这项研究已评估了 758 名来自特应性家庭的婴儿。到 3 岁为止，我们的队列保留率为 88%，其中 87% 完全符合研究要求。 3 岁以下的婴儿每年接受体检，并每年进行 15 种空气过敏原的皮肤点刺测试 (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 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 DEP、气源性过敏原和烟草烟雾 (ETS) 的独立或联合暴露与婴儿过敏、过敏性鼻炎和/或喘息之间存在显着关联。美国参议院已使用这些研究结果来支持 2005 年柴油减排法案。此外，我们的研究结果影响了临床评估，因为没有其他研究在婴儿期测试过 15 种空气过敏原。我们发现，1 岁和 2 岁时，分别有 18% 和 36% 的婴儿对空气过敏原为 SPT+。此外，我们的结果显示了显着的基因：环境相互作用。例如，GSTP1 IV/W 基因型和 DEP 暴露最高 (>0.5 A/g/m3) 的婴儿明显更容易出现喘息 (18% vs 38%，p<0.01)。此外，我们还发现，对于 ETS 暴露高且 IL4 C-589T 的 CT/TT 基因型的非裔美国人，喘息的风险增加十倍。总之，这项研究有可能对公共健康产生重大影响，因为过敏性疾病是儿童最常见的慢性疾病。这项研究有望做出额外的创新贡献，以帮助减少与常见环境暴露相关的儿童过敏发病率和死亡率。