Childhood Allergy and the NeOnatal Environment (CANOE) ECHO Pediatric Follow-Up and New Enrollment

儿童过敏和新生儿环境 (CANOE) ECHO 儿科随访和新入组

• 批准号: 10744839
• 负责人: Anne Marie Singh
• 金额: $ 128.63万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10744839
• 关键词: Affect; Age; Air Pollution; Allergic; Allergic Disease; Asthma; Atopic Dermatitis; Bacteria; Biological Markers; Biology; Birth; Calendar; Censuses; Characteristics; Child; Childhood; Childhood Asthma; Clinical; Communities; Complex; Conceptions; DNA Methylation; Data; Development; Diagnosis; Disease; Disparity; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epigenetic Process; Epithelial Cells; Epithelium; Ethnic Origin; Exposure to; Functional disorder; Funding; Gene Expression; Gene Expression Profile; Genetic; Genetic Risk; Genetic Transcription; Geography; Goals; Green space; Health Promotion; Household; Human; Hypersensitivity; Incidence; Individual; Individual Adjustment; Infant; Inflammation; Intervention; Life; Link; Low income; Mediating; Modification; Molecular; Molecular Target; Nasal Epithelium; Neighborhoods; Neonatal; Newborn Infant; Nose; Participant; Pathogenesis; Pathogenicity; Pathway interactions; Pattern; Population Density; Positioning Attribute; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention strategy; Protocols documentation; Publishing; Race; Recurrence; Risk; Skin; Skin colonization; Structure; Swab; Technology; Testing; Wheezing; Woman; airway epithelium; allergic response; asthma exacerbation; asthma prevention; bacterial community; cohort; data harmonization; disparity reduction; early life exposure; follow-up; gene environment interaction; health disparity; immune activation; infancy; insight; microbial colonization; microbiome; multidisciplinary; multiple omics; prenatal; programs; recruit; respiratory; response; sex; skin microbiome; social health determinants; transcriptomics; treatment strategy

PROJECT ABSTRACT Asthma is a complex, heterogenous condition with both genetic and environmental factors contributing to disease. The epithelial barrier is the interface between environmental exposures and the host. Gene- environment interaction studies demonstrate that early life exposures modify genetic risks in asthma, and epigenetic changes, such as DNA methylation (DNAm) may mediate these effects. Additionally, epithelial transcriptional changes link to childhood asthma. We propose to use both of these powerful technologies to provide a mechanistic link from environmental exposure to asthma inception. We hypothesize that exposures at the epithelial barrier related to the community (air pollution, nearby green space) and the individual (microbiome) alter epithelial DNAm and transcriptional responses to promote the development of asthma. To evaluate this hypothesis, we will leverage the ECHO Cohort protocol 3.0 to determine how prenatal and early life individual and neighborhood level exposures contribute to nasal epithelial changes in infancy to promote the development of wheezing (aim 1), determine how the these exposures, including the skin microbiome, influence skin epithelial changes to promote atopic dermatitis and wheezing (aim 2), and elucidate how individual and neighborhood characteristics influence maternal nasal epigenetic changes throughout pregnancy, and how these changes relate to allergic diseases in the child (aim 4). Finally, we will follow existing ECHO participants and recruit 350 pregnant women and 50 women preconception that give birth (for a of total 400 births) into ECHO Cohort protocol 3.0 (aim 3). Importantly, throughout this proposal, we seek to disentangle factors that may underlie health disparities by identifying the mechanisms by which environmental exposures (that are often associated and conflated with race) cause asthma. We will identify precise molecular targets for diagnosis and prevention. This information can be used to (1) establish non-invasive biomarkers (from nasal or skin swabs) to identify infants at risk for asthma, (2) develop treatment strategies based on altering patterns of microbial colonization or epithelial gene expression to promote health, and (3) identify actionable exposures that underly health disparities for intervention.

项目摘要 哮喘是一种复杂的异质疾病 疾病。上皮屏障是环境暴露与主机之间的接口。基因- 环境互动研究表明，早期生活会暴露于哮喘中的遗传风险，并 表观遗传变化，例如DNA甲基化（DNAM）可能会介导这些作用。另外，上皮 转录变化与儿童哮喘有关。我们建议使用这两种强大的技术来 提供从环境暴露到哮喘开始的机械联系。我们假设暴露 在与社区有关的上皮障碍（空气污染，附近的绿色空间）和个人 （微生物组）改变上皮dnam和转录反应以促进哮喘的发展。到 评估这一假设，我们将利用Echo队列协议3.0来确定产前和早期 生活中的个人和邻里水平暴露会导致婴儿期鼻上皮变化以促进 喘息的发展（AIM 1），确定包括皮肤微生物组在内的这些暴露方式如何 影响皮肤上皮变化，以促进特应性皮炎和喘息（AIM 2），并阐明如何 个人和邻居特征会影响母亲鼻遗传学变化 怀孕以及这些变化如何与儿童的过敏性疾病有关（AIM 4）。最后，我们将跟随 现有的Echo参与者和招募350名孕妇和50名妇女先入出生的妇女（对于 总共400个出生）进入回声队列方案3.0（AIM 3）。重要的是，在整个提案中，我们寻求 通过确定环境的机制，可能是健康差异的基础的分解因素 暴露（通常与种族相关联）会导致哮喘。我们将确定精确的分子 诊断和预防的目标。此信息可用于（1）建立非侵入性生物标志物 （从鼻或皮肤拭子）确定哮喘风险的婴儿，（2）基于 改变微生物定植或上皮基因表达以促进健康的模式，（3）确定 可操作的暴露措施是基本的健康差异以进行干预。