PATHOGENESIS OF CHILDHOOD ASTHMA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。COSTAR(儿童哮喘起源)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。这项研究招募了312名患有特应性疾病的高危儿童(父母一方或双方都有过敏和/或哮喘)。研究儿童哮喘是复杂的，因为(A)在没有哮喘相关症状的情况下可能会发生喘息，(B)很难获得相关的生物标本进行分析，(C)需要在导致这种复杂疾病的遗传和环境相互作用的背景下研究免疫和肺部系统。为了解决这些重要问题，研究人员使用了项目资助(PPG)格式(3个项目和3个核心)来实施一种综合的方法来进行免疫学、微生物学、流行病学、生理学、分子和遗传学评估，包括在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，这种发展可能会受到病毒呼吸道感染和基因-环境相互作用的进一步影响，这些相互作用始于子宫，一直持续到婴儿和儿童早期。正在研究环境、基因表达、病毒疾病和免疫发育之间的相关性，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.