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

基本信息

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
项目类别：
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

项目摘要

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性疾病，遗传和环境因素共同导致疾病。上皮屏障是环境暴露与宿主之间的界面。基因- 环境相互作用研究表明，生命早期的暴露可以改变哮喘的遗传风险，并且表观遗传变化，例如 DNA 甲基化 (DNAm) 可能会介导这些影响。此外，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提供从环境暴露到哮喘发病的机制联系。我们假设暴露与社区（空气污染、附近绿地）和个人相关的上皮屏障（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 来确定产前和早期如何生活中个人和邻里水平的暴露有助于婴儿期鼻上皮的变化，从而促进喘息的发生（目标 1），确定这些暴露（包括皮肤微生物组）如何影响皮肤上皮变化以促进特应性皮炎和喘息（目标 2），并阐明如何个体和社区特征影响母亲鼻部表观遗传变化怀孕，以及这些变化与儿童过敏性疾病的关系（目标 4）。最后我们将跟随现有的 ECHO 参与者并招募 350 名孕妇和 50 名已生育的妇女（用于总共 400 名新生儿）纳入 ECHO 队列协议 3.0（目标 3）。重要的是，在整个提案中，我们力求通过确定环境影响的机制，理清可能造成健康差异的因素暴露（通常与种族相关或混为一谈）会导致哮喘。我们将鉴定精确的分子诊断和预防的目标。该信息可用于 (1) 建立非侵入性生物标志物（通过鼻腔或皮肤拭子）识别有哮喘风险的婴儿，(2) 根据以下情况制定治疗策略：改变微生物定植或上皮基因表达的模式以促进健康，以及（3）确定造成健康差异的可采取行动的暴露，以进行干预。