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

项目摘要 我们建议继续遵循种族和社会经济多样化的亨利福特健康（HFH） 儿童过敏和新生儿环境（CANOE）队列。调查组对这起谋杀案 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 - 这些问题给儿童带来了巨大的社会、经济和发展负担， ECHO程序。特应性多发性硬化的发病率和基本描述流行病学趋势 虽然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 实践中也缺乏早期生物标志物来识别患有特应性多表型的儿童，包括 患有AD、食物过敏和伴有或不伴有过敏性鼻炎的哮喘（在本文中称为严重特应性鼻炎 multimorphine [SAMM]）。环境因素可能会影响特应性的风险，DNA甲基化（DNAm）是 受环境因素的影响，并可通过以下途径促进免疫途径向过敏表型发展： 基因调控对胎盘DNAm进行了有限的研究，胎盘DNAm是一种生物学相关组织， 评估产前暴露可能影响特应性的风险，并作为SAMM风险的早期生物标志物。我们 假设SAMM的发病率根据人口统计学因素而变化。我们还假设， 有SAMM风险的婴儿具有可能受环境因素影响的差异胎盘DNAm。的 该提案的具体目标是：（1）确定ECHO范围内的发病率和患病率， 严重特应性多发性骨髓瘤（SAMM）在6岁时明显，其人口统计学因素包括年龄，性别， （2）确定胎盘DNAm的改变是否能区分患有 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，公平和包容原则，以连接和参与研究参与者， 加强和完成ECHO研究活动和方案，为期7年;并利用参与者 顾问，以扩大参与者的声音，并克服参与和保留的挑战。的 根据这一建议所产生的数据，再加上欧洲人道主义组织范围内的数据，将能够准确地估计发病率 共病特应性疾病表型的发生率，是了解胎盘如何 可能会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标本， 从出生到童年中期的队列将是ECHO研究的基本资产 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 CANOE队列的持续随访将允许以解决方案为导向的调查 健康和疾病的原因和贡献者。

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.