Children's Respiratory and Environmental Workgroup (CREW)

项目摘要/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、感染模式和定居 病毒和细菌，以及心理社会压力。尽管取得了这些进展，但在理解 哮喘的根本原因至少受到两个因素的阻碍。一、程序和科学方法 在队列中没有标准化，这使得比较和验证研究结果变得困难。第二，哮喘 不同人群的定义差别很大。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”)的哮喘 内型“)。我们假设宿主因素(遗传学、表观遗传学)与环境相互作用 胎儿期和儿童早期暴露导致儿童特定内型 哮喘。我们进一步提出，在生命早期识别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，单一群体的识别能力有限。 哮喘内型由于样本量小和独特的人群特征。克服缺点 在个人队列中，领导全美12个哮喘出生队列的研究人员现在提出 成立儿童呼吸系统研究和环境工作组(“CREW”)联盟。这 该联盟建议通过以下方式确定哮喘内型并克服个别队列的缺点：1) 提供大量(近9000名新生儿和6000-7000名儿童和年轻人的长期随访)和 多样化的国家数据集，2)统一与哮喘临床指标和早期生活环境相关的数据 暴露，3)为船员队列中的前瞻性数据收集制定标准化措施，以及 其他回声研究，以及4)有针对性地将更多的受试者纳入现有队列。这 方法将允许收集针对系统方法进行优化的样本，以了解 早期生活中的环境和宿主因素促进特定哮喘内型的发展。 总体而言，这项综合研究的结果是确定哮喘的根本原因与弹性和 健康将远远超出个人群体所能完成的范围，从而为 今后的努力旨在个性化预防儿童慢性哮喘。

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.