PATHOGENESIS OF CHILDHOOD ASTHMA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。COAST（哮喘的儿童起源）是一项前瞻性出生队列研究，旨在探讨年龄、细胞因子分泌模式和病毒感染之间的相互作用与哮喘和过敏性疾病的后续发展。该研究招募了312名患有特应性疾病的高风险儿童（父母一方或双方患有过敏和/或哮喘）。研究儿童哮喘是复杂的，因为（a）喘息可以在没有哮喘相关症状的情况下发生，（B）获得相关生物样本进行分析是困难的，以及（c）免疫和肺系统需要在遗传和环境相互作用的背景下进行研究，这有助于这种复杂的疾病。 为了解决这些重要问题，研究人员使用了计划项目资助（PPG）形式（3个项目和3个核心）来实施一种综合方法，以进行免疫学、微生物学、流行病学、生理学、分子学和遗传学评价，这些评价涉及人体受试者的体外和体内模型。 该假说认为免疫失调是儿童哮喘发病的关键因素，而且这种发展可能进一步受到病毒性呼吸道感染和基因-环境相互作用的影响，这些相互作用开始于子宫内，并在整个婴儿期和幼儿期持续存在。环境，基因表达，病毒性疾病和免疫发育之间的相关性正在研究中，以了解各种儿童过敏性疾病和哮喘的表达，进展，加重和/或消退。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. COAST (Childhood Origins of ASThma) is a prospective birth cohort study designed to address the interactions among age, patterns of cytokine secretion, and virus infections with respect to the subsequent development of asthma and allergic diseases. The study enrolled 312 children at high risk of developing atopic diseases (one or both parents have allergies and/or asthma.) Studying childhood asthma is complex because (a) wheezing can occur without the correlated symptoms of asthma, (b) obtaining relevant biologic specimens for analyses is difficult, and (c) the immune and lung system need to be studied in the context of both genetic and environmental interactions which contribute to this complex disorder. To address these important issues, the investigators have used a Program Project Grant (PPG) format (3 projects and 3 cores) to implement an integrated approach to conducting immunological, microbiological, epidemiological, physiological, molecular, and genetic evaluations that involve in vitro and in vivo models in human subjects. The hypothesis is that immune dysregulation is a pivotal component in the start of childhood asthma, and that this development may be further influenced by viral respiratory tract infections and by gene-environment interactions that begin in utero and continue throughout infancy and early childhood. The correlations among environment, gene-expression, viral illness and immune development are being examined to understand the expression, progression, exacerbation and/or regression of various childhood allergic diseases and asthma.