ECHO Renewal for the INSPIRE Study Cohort

摘要 该提案的总体目标是：1）保持INSPIRE出生时的儿童保留率 强调多样性的队列，以及高保真的ECHO队列方案的实施，以及2） 解决儿童哮喘诊断和管理方面的主要局限性-解决需要确定 哮喘表型和内型，以制定有针对性的治疗和预防策略。 术语哮喘是具有不同临床变量的几种疾病状态的总括诊断。 呈现（表型）和机制途径（内型）。理解这些因素的因果作用 环境暴露在哮喘发展和疾病管理中的作用是识别不同的哮喘 表型本提案的科学目标是：1）目标1：确定发病率和患病率 两种高度相关的哮喘表型，特应性和非特应性哮喘，按年龄，性别，队列十年， 地理位置，使用广泛可用和统一的变量以及通过欧盟人道处收集的变量 队列方案。我们还将确定已建立的环境风险和保护的贡献 与这些特定的临床相关哮喘表型相关的因素。最后，我们将比较 通过哮喘表型估计儿童哮喘发病率; 2）目的2：进一步表征哮喘 表型和内型转化为临床有用的实体内ECHO财团和扩大的发现 通过利用现有的或将要收集的样本来增加哮喘的常规生物标志物， 可用于临床实践，鼻样本进行转录组学分析，以确定哮喘 3）目标3：促进和监督已建立的INSPIRE队列的纵向随访，以及 收集生物样本，以最大限度地保留现有参与者，强调多样性，并实施 高保真的ECHO队列协议。INSPIRE出生队列研究是一项基于人群的出生队列研究 最初招募了超过1950名足月健康婴儿。INSPIRE在包括婴儿监测方面是独一无二的 通过每两周一次的主动和被动监测，使用PCR进行病毒检测， 呼吸道合胞病毒（RSV）血清学在1岁。孩子们将在8-10岁时， ECHO资助期结束，进入青春期，并将在接下来的15-17岁期间进行随访 融资期。 该研究是一种创新的、新颖的、多方面的和实用的方法， 从将“哮喘”视为单一的伞型疾病，以及识别和理解哮喘表型， 内型，以及风险和保护因素对特定哮喘表型的影响。我们的方法 建议也是实际的，在走向解决方案，利用目前可用的技术和实验室 测试，以帮助儿童哮喘亚型的诊断标准的发展。

ABSTRACT The overarching goals of this proposal are 1) to maintain retention of children in the INSPIRE birth cohort with emphasis on diversity, and implementation of the ECHO Cohort Protocol with high fidelity, and 2) tackle the major limitation in diagnosis and management of childhood asthma - addressing the need to identify asthma phenotypes and endotypes to develop targeted treatment and prevention strategies. The term asthma is an umbrella diagnosis for several disease states with distinct variable clinical presentations (phenotypes) and mechanistic pathways (endotypes). Central to understanding the causal role of environmental exposures in asthma development and to disease management is identifying distinct asthma phenotypes. The scientific aims of this proposal are: 1) Aim 1: to determine the incidence and prevalence of two highly relevant asthma phenotypes, atopic and non-atopic asthma, by age, sex, cohort decade and geographic location, using widely available and harmonized variables and those collected through the ECHO Cohort Protocol. We will also determine the contribution of established environmental risk and protective factors with these specific clinically relevant asthma phenotypes. Lastly, we will calculate comparative estimates of childhood asthma morbidity by asthma phenotypes; 2) Aim 2: to further characterize asthma phenotypes and endotypes into clinically useful entities within the ECHO consortium and expand the findings to clinical practice by utilizing available or to be collected samples to add biomarkers of asthma routinely available in clinical practice, and nasal samples to perform transcriptomic analyses to define asthma endotypes; 3) Aim 3: to facilitate and oversee longitudinal follow-up of the established INSPIRE cohort, and biosample collection to maximize retention of existing participants with emphasis on diversity, and implement the ECHO Cohort Protocol with high fidelity. The INSPIRE birth cohort is a population-based birth cohort study that originally enrolled over 1950 term healthy infants. INSPIRE is unique in including surveillance for infant respiratory viral infection through biweekly active and passive surveillance using PCR for viral detection and respiratory syncytial virus (RSV) serology at age one. The children will be ages 8-10 years when the current ECHO funding period ends, entering adolescence, and will be followed to age 15-17 years during this next funding period. The proposed research is an innovative, novel, multi-faceted and practical approach to move away from viewing “asthma” as a single umbrella disease, and identifying and understanding asthma phenotypes, endotypes, and the influence of risk and protective factors on specific asthma phenotypes. The approach we propose is also practical in moving toward solutions that utilize currently available technologies and laboratory testing to aide in development of diagnostic criteria for childhood asthma sub-types.