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.

项目总结 哮喘影响着大约10%的美国儿童，是呼吸道疾病和 住院治疗。哮喘不成比例地影响父母认同的黑人和加勒比拉美裔儿童，以及 环境对儿童健康结果的影响(ECHO)研究的大量和多样化的人群是 是识别哮喘差异的早期原因的理想选择。威斯康星州婴儿研究队列(WISC)是一个出生 一群服务不足的农村家庭和儿童。此群体将带来与ECHO相关的唯一数据 暴露(动物、微生物群)、邻里因素(低人口密度、清洁空气)和健康结果 (降低呼吸系统疾病的比率)。我们的科学目标集中在环境因素和荷尔蒙 青春期的影响调节鼻呼吸道细胞(NAC)的分子反应。我们将分析DNA 儿童期中期和青春期早期NAC样本的甲基化(DNaM)和基因表达 结合这些数据来识别“分子表型”。我们假设这些表型与特定的 早期生活中的环境暴露和6-10岁和三年随访期间的哮喘相关结果- 上行期。因此，我们提出以下具体目标： 目的1.为了利用ECHO协议3.0的核心数据，我们将分析NAC基因的表达和dNaM在 6-10岁儿童识别呼吸道细胞分子表型，然后测试与产前的相关性 以及出生后早期环境暴露、个人因素(性别、父母认同的种族/民族、年龄、 候选基因的多态)和临床结果(哮喘、鼻炎、肺功能)。 目标2：我们将在三年后(9-13岁)重新评估哮喘预后和鼻呼吸道细胞。 确定哮喘疾病的活动性和严重程度的变化如何与：a)6-10岁的分子表型 年，b)潜在的哮喘改善因素，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ECHO系统来 最大限度地保留现有参与者，促进与农村和农业风险敞口相关的多样性，并 生活方式，并高保真地执行回声队列协议。 这些拟议的研究将把可改变的环境暴露与呼吸道细胞和分子调节联系起来 过敏和哮喘的临床结果。结果将产生一个信息宝库，这些信息可能会为新的 预防哮喘的战略，并在受影响的儿童中，能够采取创新的方法促进疾病控制 和减刑。