Epidemiology of multimorbid pediatric atopic and airway diseases and the impact of prenatal maternal environmental exposures and placental epigenetics

多病儿科特应性和气道疾病的流行病学以及产前母亲环境暴露和胎盘表观遗传学的影响

• 批准号: 10745097
• 负责人: Amy Eapen
• 金额: $ 90.24万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 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/10745097
• 关键词: 6 year old; Address; Age; Air Pollution; Airway Disease; Allergic; Allergic Disease; Allergic rhinitis; Anxiety; Asthma; Atopic Dermatitis; Biological Markers; Birth; Categories; Child; Child Health; Childhood; Collaborations; Community Health Aides; Country; DNA Methylation; Data; Demographic Factors; Descriptive Epidemiology; Development; Diet; Disease; Disease Outcome; Early identification; Endocrine; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiological trend; Epidemiology; Epigenetic Process; Ethnic Origin; European ancestry; Family; Fetal Development; Financial Hardship; Food Aversion; Food Hypersensitivity; Gene Expression; Gene Expression Regulation; Geography; Growth; Health; Hypersensitivity; Immune; Immune system; Incidence; Infant; Intake; Intervention; Investigation; Link; Manuscripts; Maternal-Fetal Exchange; Mediating; Mental Depression; Metabolic; Methylation; Minority Groups; Neonatal; Neurocognitive Deficit; Nutrient; Organ; Outcome; Participant; Pathway interactions; Pattern; Persons; Phenotype; Physical activity; Placenta; Population; Populations at Risk; Prevalence; Prevention; Protocols documentation; Quality of life; Race; Research; Research Personnel; Risk; Risk Factors; Role; School-Age Population; Site; Sleep disturbances; Target Populations; Time; Tissues; United States National Institutes of Health; Voice; Whole Blood; atopy; burden of illness; clinical practice; cohort; comorbidity; design; disease phenotype; disorder risk; early detection biomarkers; early life exposure; equity, diversity, and inclusion; fetal; follow-up; improved; innovation; interest; intrauterine environment; maternal stress; methylation pattern; methylome; middle childhood; multiple chronic conditions; obesity in children; offspring; potential biomarker; predictive marker; pregnant; prenatal; prenatal environmental exposure; prenatal exposure; prenatal influence; prevent; programs; sex; social; socioeconomics; working group

Project summary We propose to continue to follow the racially and socioeconomically diverse Henry Ford Health (HFH) Childhood Allergy and the Neonatal Environment (CANOE) cohort. The investigative team has specific interest in the prevention of atopic diseases – including atopic dermatitis (AD), food allergy, asthma and allergic rhinitis – which pose a significant social, financial, and developmental burden for children and are a priority for the ECHO program. The incidence rates and fundamental descriptive epidemiology trends of atopic multimorbidity for children in the US are unknown, although the co-existence of multiple atopic disorders contributes to a significant detriment in health and development, including neurocognitive deficits and poor growth. Clinical practice also lacks an early biomarker to identify the children with atopic multimorbidity phenotypes, including those with AD, food allergy, and asthma with or without allergic rhinitis (referred to herein as severe atopic multimorbidity [SAMM]). Environmental factors may impact risk of atopy, and DNA methylation (DNAm) is influenced by environmental factors and can promote immune pathways towards an allergic phenotype through gene regulation. Limited investigations have been done on placental DNAm, a biologically relevant tissue for assessing prenatal exposures that may influence risk of atopy and act as an early biomarker of SAMM risk. We hypothesize that the incidence rates of SAMM vary based on demographic factors. We also hypothesize that infants at risk of SAMM have differential placental DNAm that may be influenced by environmental factors. The Specific Aims for this proposal are to: (1) Determine ECHO-wide incidence rates and prevalence over time of severe atopic multimorbidity (SAMM) evident by the age of 6 years by demographic factors including age, sex, race/ethnicity, and geography; (2) Determine whether placental DNAm alterations differentiate children with SAMM and if they are influenced by prenatal environmental exposures; and (3) Utilize community health workers and diversity, equity, and inclusion principles to connect and engage with study participants to enhance and complete ECHO study activities and protocols for an additional 7 years; and utilize participant advisors to amplify the voices of participants and overcome challenges with engagement and retention. The data generated by this proposal, combined with ECHO-wide data, will allow for accurate estimates of incidence rates of co-morbid atopic disease phenotypes and is an important step toward understanding how the placenta may influence allergic disease risk. Most importantly, the data and biospecimens that will be generated by this cohort as it ages from birth through middle childhood will be a fundamental asset for the ECHO research platform as numerous investigators all over the country utilize these data to address child health and disease for years to come. Continued follow-up of the HFH CANOE cohort will allow for solution-oriented investigations into causes and contributors to health and disease.

项目摘要 我们建议继续遵循种族和社会经济多样的亨利·福特健康（HFH） 儿童过敏和新生儿环境（独木舟）队列。调查团队特别感兴趣 在预防特应性疾病中 - 包括特应性皮炎（AD），食物过敏，哮喘和过敏性鼻炎 - 这对儿童构成了重大的社会，财务和发展烧伤，并且是 回声程序。特征多发病的发病率和基本描述性流行病学趋势 对于美国的儿童来说，尚不清楚，尽管多种特应性疾病的并存有助于 健康和发展的严重损害，包括神经认知缺陷和增长不佳。临床 实践还缺乏早期的生物标志物来识别患有特应多发病表型的儿童，包括 患有AD，食物过敏和哮喘患有或没有过敏性鼻炎的患者 多种病态[SAMM]）。环境因素可能会影响特应性的风险，而DNA甲基化（DNAM）为 受环境因素的影响，可以通过 基因调节。对Placenal Dnam进行了有限的研究，PlaceNal DNAM是一种生物学相关的组织 评估可能影响特应性风险并起到SAMM风险的早期生物标志物的产前暴露。我们 假设SAMM的事件率根据人口因素而有所不同。我们还假设 患有SAMM风险的婴儿可能会受到环境因素的影响，可能会受到不同的影响。这 该提案的具体目的是：（1）确定随着时间的流逝，确定范围范围的发病率和患病率 严重的特应特应多种病（SAMM）的证据到6岁，包括年龄，性别，性别，性别因素 种族/种族和地理； （2）确定placenal dnam是否改变了儿童 SAMM，如果它们受到产前环境暴露的影响； （3）利用社区健康 工人和多样性，公平和包容性原则，与研究参与者联系并与 增强并完成回声研究活动和协议，以又有7年的速度；并利用参与者 扩大参与者的声音并克服参与和保留的挑战的顾问。 该提案生成的数据，结合了回声范围的数据，将允许对事件进行准确的估计 摩尔腹性特应性疾病表型的速率，是了解多余的重要一步 可能会影响过敏性疾病风险。最重要的是，将生成的数据和生物测量 从出生到中年的同龄人队列将是回声研究的基本资产 平台作为全国各地的众多调查人员都利用这些数据来解决儿童健康和疾病 未来几年。 HFH独木舟队列的持续随访将允许以解决方案为导向的研究 成为健康和疾病的原因和贡献者。