Etiology of Pediatric Atopy

小儿特应性的病因学

• 批准号: 6897306
• 负责人: EDWARD M ZORATTI
• 金额: $ 65.22万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897306
• 关键词: adolescence (12-20); allergens; asthma; biomarker; clinical research; disease /disorder etiology; domestic animals; early experience; environmental exposure; family genetics; gene environment interaction; genetic registry /resource /referral center; helper T lymphocyte; human subject; immune response; immunoglobulin E; immunoglobulin G; interferon gamma; interleukin 10; interleukin 4; leukocyte activation /transformation; questionnaires; respiratory disorder epidemiology; rhinitis; tissue resource /registry

DESCRIPTION (provided by applicant): Our objective is to study the relationship of early-life cat and dog exposure to potential persistent effects on T-cell cytokine profiles, biologic markers of atopy, and clinical atopy among a well-characterized birth cohort (n=835), the Detroit area Childhood Allergy Study (CAS), as they reach 18 years of age. Extensive early-life environmental exposure data have been collected on this cohort. Outcomes will include total IgE, allergen-specific IgE and IgG4 levels, intracellular IL-4, IL-10 and interferon (IFN)gamma in mitogen stimulated T-cells and current or history of allergic rhinitis and asthma. Hypotheses: Compared to subjects with low levels of exposure, those with high-level exposure to dogs and cats in the first year of life will exhibit: i) a persistently altered immune response at age 17, typified by a low IL-4/IFN-gamma ratio and elevated IL- 10 secretion in response to T-cell mitogenic stimulation; ii) reduced levels of allergenspecific IgE and increased allergen-specific IgG4 to common aeroallergens; and, iii) a persistently reduced risk for allergic rhinitis and asthma. The specific aims include analyzing the number of indoor pets during the first year of life, adjusting for well-established confounders and effect modifiers, for persistent effects on: i) T-cell intracellular cytokine levels of IL-4, IFN-gamma and IL-10; ii) serum levels of allergen-specific IgE (cat, dog, dust mite, ragweed, grass and alternaria) and allergen-specific IgG4 (cat, dog, grass and dust mite); iii) current and lifetime history of self-reported and doctor diagnosed allergic rhinitis and asthma. We will also iv) study the relationship between these outcomes and v) evaluate the role of biomarkers and history of atopy in each parent in the above analyses. Methods: The CAS cohort will be followed-up by questionnaire and a home visit at age 18 years. Stimulated T cell cytokine analysis, total IgE and serum allergen-specific IgE and IgG4 levels will be determined and cohort subjects and parents will answer a questionnaire regarding subject and parental history of symptoms and diagnosis of allergic rhinitis and asthma and post early life pet exposure. Blood specimens, DNA and mRNA from parents and subjects will be placed in a biorepository for future molecular epidemiology studies.

描述（由申请人提供）：我们的目的是研究在底特律地区儿童过敏研究（CAS）中，在一个充分表征的出生队列（n=835）中，当猫和狗达到18岁时，其早期接触对T细胞细胞因子谱、特应性生物标志物和临床特应性的潜在持续影响的关系。已经收集了关于这一队列的大量早期生活环境暴露数据。结局将包括总IgE、过敏原特异性IgE和IgG 4水平、细胞内IL-4、IL-10和有丝分裂原刺激的T细胞中的干扰素（IFN）γ以及当前或过敏性鼻炎和哮喘病史。假设条件：与低水平暴露的受试者相比，在出生后第一年内高水平暴露于狗和猫的受试者将表现出：i）在17岁时持续改变的免疫应答，典型表现为低IL-4/IFN-γ比率和响应于T细胞促有丝分裂刺激的升高的IL- 10分泌; ii）降低的变应原特异性IgE水平和增加的对常见空气变应原的变应原特异性IgG 4;和iii）持续降低变应性鼻炎和哮喘的风险。具体目的包括分析出生后第一年室内宠物的数量，调整已确立的混杂因素和效应调节剂，调整对以下的持续效应：i）IL-4、IFN-γ和IL-10的T细胞细胞内细胞因子水平; ii）过敏原特异性IgE的血清水平（猫、狗、尘螨、豚草、草和链格孢属）和过敏原特异性IgG 4（猫、狗、草和尘螨）; iii）自我报告和医生诊断的过敏性鼻炎和哮喘的当前和终生病史。我们还将iv）研究这些结果之间的关系，以及v）在上述分析中评价生物标志物和特应性病史在每个父母中的作用。方法：CAS队列将通过问卷调查和18岁时的家庭访视进行随访。将测定刺激的T细胞细胞因子分析、总IgE和血清过敏原特异性IgE和IgG 4水平，队列受试者和父母将回答关于受试者和父母症状史、过敏性鼻炎和哮喘诊断以及早期宠物暴露后的问卷。来自父母和受试者的血液标本、DNA和mRNA将被放置在生物储存库中，用于未来的分子流行病学研究。