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

项目总结 我们建议继续关注种族和社会经济多元化的亨利·福特健康公司(Henry Ford Health，HFH) 儿童过敏与新生儿环境(独木舟)队列。调查组有特殊的兴趣 预防特应性疾病，包括特应性皮炎、食物过敏、哮喘和过敏性鼻炎 --对儿童造成重大的社会、经济和发展负担，是 Echo程序。特应性多发病的发病率和基本描述性流行病学趋势 在美国对儿童的影响是未知的，尽管多种特应性疾病的共存有助于 严重损害健康和发育，包括神经认知缺陷和发育不良。临床 实践也缺乏早期生物标记物来识别患有特应性多病表型的儿童，包括 患有阿尔茨海默病、食物过敏和哮喘并或不伴有过敏性鼻炎(本文称为严重特应症)的人 多发病[SAMM])。环境因素可能影响特应性疾病的风险，而DNA甲基化(DNaM)是 受环境因素影响，并可通过以下途径促进免疫途径向过敏表型转变 基因调控。对胎盘dNaM的研究有限，胎盘dNaM是一种与 评估产前暴露可能影响特应性反应的风险，并作为SAMM风险的早期生物标记物。我们 假设SAMM的发病率因人口因素而异。我们还假设 有SAMM风险的婴儿胎盘dNaM不同，可能受环境因素的影响。这个 这项建议的具体目标是：(1)确定随时间推移的全回声发生率和患病率 严重的特应性多病(SAMM)在6岁时明显，人口统计因素包括年龄，性别， 种族/民族和地理位置；(2)决定胎盘dNaM改变是否会区分儿童与 如果他们受到产前环境暴露的影响；以及(3)利用社区卫生 工作人员和多样性、公平和包容性原则，以联系和参与研究参与者 在另外7年内加强和完成ECHO研究活动和方案；并利用参与者 顾问扩大参与者的声音，并通过参与和留住来克服挑战。这个 这一提议产生的数据，与回声范围的数据相结合，将能够准确地估计入射 特应性疾病表型的共病发生率是了解胎盘如何 可能影响过敏性疾病的风险。最重要的是，这将产生的数据和生物量 从出生到童年中期的队列将是ECHO研究的基本资产 平台，因为全国各地的许多调查人员利用这些数据来解决儿童健康和疾病问题 在未来的几年里。对HFH独木舟队列的持续跟踪将使以解决方案为导向的调查成为可能 健康和疾病的起因和贡献者。

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.