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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