Cytokine Dysregulation, Virus Infections, And Asthma

对病毒感染的免疫反应异常和某些呼吸道的毒力模式 病毒已被认为在疾病的发生、发展和严重程度上起着重要作用。 儿童哮喘的发病机制不明。使用出生队列来研究这些关系， 我们对免疫反应图谱进行了一些新的和重要的观察 和早期的病毒感染，以及最近随着队列的持续成熟，我们 把这些发现放在基因-环境相互作用，发育方面， 和性别差异。到目前为止，最新的发现是中度到重度鼻病毒 婴儿期(RV)诱发的喘息性疾病是早期生命中最重要的事件 预测儿童哮喘的后续发展。此外，这些结果似乎是 与干扰素产生不足有关，以应对这些感染。因此， 这个项目的总体假设是，易感性、临床严重性和临床表现 儿童和青春期早期的轮状病毒感染与干扰素缺乏有关 对病毒感染的反应。因此，我们建议继续评估细胞因子的反应 三个组织隔间(血液、鼻腔抽吸物和诱导痰)的特征 先前存储的和预期获得的，因为它们与发育和生理 喘息性疾病与特定病毒病原体的后果，各种特应性疾病的发展 表型与婴儿期、儿童期和早期哮喘的表现和缓解 青春期。该项目包括整个海岸队列，除了它自己的具体目标之外 和目标，提供所有的表型特征和生物标本以及DMA 此应用程序中的其余项目。定义病毒感染影响人类健康的机制 儿童哮喘的临床表现显然与针对以下疾病的治疗方法的发展有关 既有药物形式的急性治疗，也有疫苗形式的初级预防。

Abnormalities in immune response to viral infections and the virulence patterns of certain respiratory viruses have been felt to contribute significantly to the inception, progression, and severity of childhood asthma through unknown mechanisms. Using a birth cohort to study these relationships, we have made a number of novel and important observations pertaining to immune response profiles and virus infections during early life, and more recently with continued maturation of the cohort, we have placed these findings in the context of gene-environment interactions, developmental aspects, and gender differences. The most novel finding thus far has been that moderate to severe rhinovirus (RV)-induced wheezing illnesses during infancy are the most significant event in early life that predicts the subsequent development of childhood asthma. Moreover, these outcomes appear to be related to deficiencies in the production of interferons in response to these infections. Thus, the overall hypothesis of this project is that susceptibility to, and the clinical severity and manifestations of RV infections throughout childhood and early adolescence, is related to a deficiency in interferon responses to viral infection. We therefore propose to continue evaluation of cytokine response profiles from three tissue compartments (blood, nasal aspirates, and induced sputum) that have been previously stored and prospectively obtained as they relate to the development and physiological consequences of wheezing illnesses with specific viral pathogens, the development of various atopic phenotypes, and the expression and remission of asthma through infancy, childhood and early adolescence. This project comprises the entire COAST cohort that, in addition to its own specific aims and objectives, provides all of the phenotypic characterization and biologic specimens and DMA for the remaining projects in this application. Defining mechanisms by which viral infections impact on the clinical expression of childhood asthma is clearly relevant to the development of therapies aimed at both acute treatment in the form of medications and primary prevention in the form of vaccines.