Children's Respiratory and Environmental Workgroup (CREW)

项目总结/摘要 个体出生队列研究已经确定了儿童哮喘的危险因素，包括 早期生活中的环境暴露，如过敏原、污染物、感染模式和 病毒和细菌以及心理压力。尽管取得了这些进展， 哮喘的根本原因至少受到两个因素的阻碍。一是程序和科学方法 在各队列中没有标准化，因此难以比较和验证结果。二、哮喘 各群组的定义差别很大。事实上，哮喘是一种综合征;有不同的亚型， 具有不同临床特征（“哮喘表型”）和可能不同病因（“哮喘 endotypes”）。我们假设宿主因素（遗传学，表观遗传学）与环境相互作用， 在产前和幼儿期的暴露，导致儿童期的特定内型 哮喘我们进一步提出，在早期生命中鉴定内型和相关的分子生物标志物 可以为哮喘的预防提供一个新的范例。不幸的是，单一群体识别能力有限 哮喘内型由于样本量小和独特的人群特征。克服缺点 研究人员领导了美国12个哮喘出生队列，现在提出了 成立儿童呼吸研究与环境工作组（CREW）联盟。这 联盟建议通过以下方式识别哮喘内源性并克服个体队列的缺点：1） 提供了一个大的（近9000例分娩和6000-7000名儿童和年轻人的长期随访）， 不同的国家数据集，2）协调与哮喘临床指标和早期生活环境相关的数据 暴露，3）制定CREW队列前瞻性数据收集的标准化措施， 其他ECHO研究，以及4）将额外受试者定向招募到现有队列中。这 方法将使样本的收集是优化的系统方法，以了解如何 生命早期的环境和宿主因素促进特定哮喘内型的发展。 总的来说，这项全面研究的结果，以确定哮喘的根本原因与弹性， 健康将远远超出个人群体所能实现的，从而为 未来的努力旨在个性化预防慢性儿童哮喘。

PROJECT SUMMARY/ABSTRACT Individual birth cohort studies have identified risk factors for developing childhood asthma, including environmental exposures in early life such as allergens, pollutants, patterns of infection and colonization with viruses and bacteria, and psychosocial stress. Despite such advances, further progress in understanding the root causes of asthma have been hampered by at least two factors. First, procedures and scientific methods are not standardized across cohorts, making it difficult to compare and validate findings. Second, asthma definitions across cohorts vary considerably. In fact, asthma is a syndrome; there are different subtypes of asthma with distinct clinical features (“asthma phenotypes”) and likely different etiologies (“asthma endotypes”). We hypothesize that host factors (genetics, epigenetics) interact with environmental exposures during the prenatal period and early childhood to cause specific endotypes of childhood asthma. We further propose that identification of endotypes and associated molecular biomarkers in early life can provide a new paradigm for asthma prevention. Unfortunately, single cohorts have limited ability to identify asthma endotypes due to small sample size and unique population characteristics. To overcome shortcomings of individual cohorts, investigators leading 12 asthma birth cohorts across the U.S. now propose the establishment of the Children's Respiratory Research and Environment Workgroup (“CREW”) consortium. This consortium proposes to identify asthma endotypes and overcome shortcomings of individual cohorts by: 1) providing a large (nearly 9000 births and long-term follow-up of 6000-7000 children and young adults) and diverse national data set, 2) harmonizing data related to asthma clinical indicators and early life environmental exposures, 3) developing standardized measures for prospective data collection across CREW cohorts and other ECHO studies, and 4) conducting targeted enrollment of additional subjects into existing cohorts. This approach will enable collection of samples that are optimized for a systems approach to understanding how environmental and host factors in early life promote the development of specific asthma endotypes. Collectively, the results of this comprehensive research to identify the root causes of asthma vs. resilience and health will go far beyond what can be accomplished by individual cohorts, and thus provide a foundation for future efforts aimed at personalized prevention of chronic childhood asthma.