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

项目摘要 哮喘影响大约10%的美国儿童，并且是呼吸道疾病的主要原因， 住院哮喘对父母确定的黑人和加勒比海西班牙裔儿童有不良影响， 环境对儿童健康结果的影响（ECHO）研究中的大量和多样化的人群， 非常适合于确定哮喘差异的早期原因。威斯康星州婴儿研究队列（WISC）是一个出生 贫困农村家庭和儿童。这一人口将为欧盟人道处提供独特的数据， 暴露（动物、微生物组）、邻里因素（低人口密度、清洁空气）和健康结果 （减少呼吸道疾病）。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气道细胞（NAC）的分子反应。我们会分析DNA 在儿童中期和青春期早期的NAC样本中， 联合收割机将这些数据结合起来以鉴定"分子表型"。我们假设这些表型与特定的 生命早期的环境暴露和6 - 10岁及3年随访期间的哮喘相关结局- 上时期。因此，我们提出以下具体目标： 目标1.为了利用ECHO协议3.0核心数据，我们将分析NAC基因表达和DNAm， 儿童年龄6 - 10岁，以确定气道细胞分子表型，然后测试与产前 和出生后早期环境暴露，个人因素（性别，父母确定的种族/民族，年龄， 候选基因的多态性）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）重新评估哮喘的结果和鼻气道细胞， 确定哮喘疾病活动性和严重程度的变化如何与：a）6 - 10的分子表型 年，B）潜在的哮喘调节因子，如性激素、胰岛素抵抗和过敏，和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， 最大限度地保留现有参与者，促进与农村和农业接触有关的多样性， 生活方式，并以高保真度实施ECHO队列协议。 这些拟议的研究将把可改变的环境暴露与气道细胞的分子调节联系起来， 过敏和哮喘的临床结果。结果将产生一个信息宝库，可以告知新的 制定预防哮喘的战略，并在受影响的儿童中采用创新方法来促进疾病控制 和缓解。

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.