Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-Up

威斯康星州婴儿研究队列 (WISC) ECHO 儿科随访

• 批准号: 10744843
• 负责人: James E. Gern
• 金额: $ 67.89万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744843
• 关键词: Adolescence; Adopted; Affect; Age; Air; Airway Disease; Animals; Antibiotics; Area; Asthma; Atopic Dermatitis; Biodiversity; Birth; Black race; Candidate Disease Gene; Caribbean Hispanic; Cells; Child; Child Health; Childhood; Childhood Asthma; Clinical; Cohort Studies; DNA Methylation; DNA analysis; Dairying; Data; Data Pooling; Development; Disease; Disease remission; Disparity; Early identification; Economics; Emerging Technologies; Environment; Environmental Exposure; Environmental Risk Factor; Epithelial Cells; Ethnic Origin; Exposure to; Family; Farm; Gene Expression; Genes; Genetic; Genetic Polymorphism; Geography; Goals; Gonadal Steroid Hormones; Health; Healthcare; Hormonal; Hospitalization; Hypersensitivity; Immune; Incidence; Infant; Insulin Resistance; Life; Life Style; Link; Lung; Mental Depression; Meta-Analysis; Microbe; Molecular; Neighborhoods; Nose; Nursery Schools; Outcome; Outcome Study; Parents; Participant; Pathogenicity; Phase; Phenotype; Population; Population Density; Population Heterogeneity; Poverty; Protocols documentation; Publishing; Race; Recurrence; Regulation; Reporting; Resolution; Respiratory Disease; Rhinitis; Risk; Risk Reduction; Rural; Rural Community; Rural Population; Sampling; School-Age Population; Severities; Stress; Syndrome; System; Testing; Underserved Population; United States National Institutes of Health; Update; Viral; Wheezing; Wisconsin; airway epithelium; airway obstruction; care burden; cohort; comorbidity; demographics; disorder control; disorder risk; early adolescence; early life exposure; follow-up; health disparity populations; infancy; innovation; insight; microbial; microbiome; molecular phenotype; pediatric health outcomes; pet animal; postnatal; prenatal; prevent; programs; pulmonary function; respiratory; respiratory morbidity; response; rural area; rural families; rural underserved; sex

PROJECT SUMMARY Asthma affects approximately 10% of US children and is a leading cause of respiratory morbidity and hospitalization. Asthma disproportionally affects parent-identified Black and Caribbean Hispanic children, and the large and diverse population of the Environmental Influences on Child Health Outcomes (ECHO) study is ideal for identifying early-life causes for asthma disparities. The Wisconsin Infant Study Cohort (WISC) is a birth cohort of underserved rural families and children. This population would bring unique data to ECHO related to exposures (animals, microbiome), neighborhood factors (low population density, clean air), and health outcomes (reduced rates of respiratory diseases). Our scientific goals focus on how environmental factors and hormonal influences in adolescence regulate molecular responses of nasal airway cells (NAC). We will analyze DNA methylation (DNAm) and gene expression from NAC samples in mid-childhood and early adolescence and combine these data to identify “molecular phenotypes.” We hypothesize that these phenotypes relate to specific environmental exposures in early life and asthma-related outcomes at ages 6-10 and during a three year follow- up period. We therefore propose the following specific aims: Aim 1. To leverage ECHO Protocol 3.0 core data, we will analyze NAC gene expression and DNAm in children ages 6-10 years to identify airway cell molecular phenotypes and then test for associations with prenatal and early postnatal environmental exposures, personal factors (sex, parent-identified race/ethnicity, age, polymorphisms of candidate genes), and clinical outcomes (asthma, rhinitis, lung function). Aim 2. We will reassess asthma outcomes and nasal airway cells three years later (ages 9-13 years) to determine how asthma disease activity and changes in severity relate to: a) the molecular phenotypes at 6-10 years, b) potential asthma modifying factors such as sex hormones, insulin resistance, and allergy, and c) changes in DNAm and gene expression. Aim 3. We propose to update and adapt existing WISC protocols and adopt new ECHO systems to maximize retention of existing participants, contribute diversity related to rural and farming exposures and lifestyles, and implement the ECHO Cohort Protocol with high fidelity. These proposed studies will link modifiable environmental exposures to molecular regulation of airway cells and allergy and asthma clinical outcomes. The results will yield a treasure trove of information that could inform new strategies to prevent asthma and, in affected children, enable innovative approaches to promote disease control and remission.

项目摘要 哮喘影响大约10％的美国儿童，是呼吸道发病率和 住院。哮喘对父母身份的黑人和加勒比西班牙裔儿童以及 环境影响对儿童健康结果的大量人群（ECHO）研究是 确定哮喘分布的早期生命原因的理想选择。威斯康星州婴儿研究队列（WISC）是出生 服务不足的农村家庭和儿童队列。该人群将为与之相关的Echo带来独特的数据 暴露（动物，微生物组），邻里因素（人口密度低，清洁空气）和健康结果 （呼吸疾病降低）。我们的科学目标集中于环境因素和马匹如何 青少年的影响调节鼻气道细胞（NAC）的分子反应。我们将分析DNA 甲基化（DNAM）和NAC样品中的基因表达和青少年早期的甲基化和基因表达 结合这些数据以识别“分子表型”。我们假设这些表型与特定 早期生命和哮喘相关的结果的环境暴露在6-10岁以及三年之后 - 上升期。因此，我们提出以下具体目标： 目的1。为了利用回声协议3.0核心数据，我们将分析NAC基因表达和DNAM 6-10岁的儿童鉴定气道细胞分子表型，然后测试与产前的关联 以及早期产后环境暴露，个人因素（性别，父母身份的种族/种族，年龄，年龄， 候选基因的多态性）和临床结果（哮喘，鼻炎，肺功能）。 AIM 2。我们将在三年后（9-13岁）重新评估哮喘结局和鼻气道细胞 确定哮喘疾病活性和严重程度的变化与：a）6-10的分子表型 b）潜在的哮喘修饰因素，例如性激素，胰岛素抵抗和过敏以及C） DNAM和基因表达的变化。 目标3。我们建议更新和调整现有的WISC协议，并采用新的回声系统 最大化现有参与者的保留率，贡献与粗糙和农业暴露有关的多样性以及 生活方式，并以高忠诚实施回声队列协议。 这些提出的研究将将可修改的环境暴露与气道细胞的分子调节联系起来 过敏和哮喘临床结果。结果将产生可通知新信息的宝库 预防哮喘和在受影响儿童中的策略促进创新方法来促进疾病控制 和缓解。