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.

项目概要 我们建议继续遵循种族和社会多元化亨利·福特健康 (HFH) 儿童过敏和新生儿环境 (CANOE) 队列特别感兴趣。 预防特应性疾病——包括特应性皮炎 (AD)、食物过敏、哮喘和过敏性鼻炎 – 这给儿童带来了重大的社会、经济和发展负担，是儿童的优先事项 ECHO 计划。特应性多发病的发病率和基本描述性流行病学趋势。 对于美国儿童来说，目前尚不清楚，尽管多种特应性疾病的共存导致了 严重损害健康和发育，包括神经认知缺陷和临床生长不良。 实践中还缺乏早期生物标志物来识别具有特应性多发病表型的儿童，包括 患有 AD、食物过敏和哮喘（伴或不伴过敏性鼻炎）的患者（本文称为严重特应性过敏） 多重发病率 [SAMM]）。环境因素可能会影响特应性的风险，而 DNA 甲基化 (DNAm) 是影响因素。 受环境因素的影响，可以通过以下途径促进免疫途径产生过敏表型 对胎盘DNAm（一种生物学相关组织）的基因调控进行了有限的研究。 评估可能影响特应性风险并作为 SAMM 风险早期生物标志物的产前暴露。 我们还发现 SAMM 的发病率因人口因素而异。 有 SAMM 风险的婴儿具有不同的胎盘 DNAm，可能受到环境因素的影响。 该提案的具体目标是： (1) 确定 ECHO 范围内的发病率和随时间变化的患病率 根据年龄、性别、 种族/族裔和地理位置；(2) 确定胎盘 DNAm 改变是否能区分患有以下疾病的儿童： SAMM 以及是否受到产前环境暴露的影响；以及 (3) 利用社区健康 工人和多样性、公平和包容性原则，与研究参与者建立联系和互动， 加强并完成另外 7 年的 ECHO 研究活动和方案并利用参与者； 顾问放大参与者的声音并克服参与和保留方面的挑战。 该提案生成的数据与 ECHO 范围内的数据相结合，将能够准确估计发病率 共病特应性疾病表型的发生率，是了解胎盘如何 最重要的是，可能会影响由此产生的数据和生物样本。 从出生到童年中期的队列将成为 ECHO 研究的基本资产 全国各地的众多研究人员利用这些数据来解决儿童健康和疾病问题 未来几年对 HFH CANOE 队列的持续跟踪将有助于开展以解决方案为导向的调查。 探究健康和疾病的原因和影响因素。