LONGITUDINAL STUDY OF ACUTE OTITIS MEDIA (AOM) DEVELOPMENT IN CHILDREN WITH

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，不一定是研究者所在机构。中耳炎（OM）是最常见的儿科疾病，被认为是多因素的，具有复杂的遗传，环境和感染病因。急性中耳炎（AOM）通常是儿童病毒性上呼吸道感染（URI）的细菌并发症。有证据表明，不同类型的病毒诱导AOM的能力不同。本研究旨在探讨病毒诱导AOM发生过程中“宿主”与“微生物”之间的关系。我们将探讨特定呼吸道病毒的致病性，以及促炎细胞因子（TNF α，IL-1b，IL-6）及其基因调控在病毒诱导AOM机制中的作用。我们将在体内和体外研究病毒诱导的AOM中细胞因子的差异表达。我们将前瞻性随访210名婴儿和儿童，有和没有急性期细胞因子基因（TNF α-308，IL-1b+3953和IL- 6-174等位基因）多态性一年。每次病毒URI发作后3周，我们将监测AOM的发生。我们将比较有和无AOM并发症的儿童呼吸道分泌物中的病毒类型和细胞因子浓度。将评价AOM发生的风险与细胞因子基因型的相关性。该研究将有助于阐明特定呼吸道病毒、促炎细胞因子及其基因调控在病毒诱导的AOM发病机制中的作用。

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. Otitis media (OM), the most common pediatric disease, is recognized to be multifactorial, with complex genetic, environmental and infectious etiologies. Acute otitis media (AOM) usually occurs as a bacterial complication of viral upper respiratory tract infection (URI) in children. Evidence suggests that different types of viruses vary in their ability to induce AOM. The proposed study will investigate the relationship between "host" and "microbe" in the development of virus-induced AOM. We will explore the pathogenicity of specific respiratory viruses, and the role of proinflammatory cytokines (TNFa, IL-1b, IL-6) and their gene regulation in the mechanisms of virus-induced AOM. We will study differential cytokine expression in virus-induced AOM in vivo and in vitro. We will prospectively follow 210 infants and children, with and without polymorphisms of acute phase cytokine genes (TNFa-308, IL-1b+3953, and IL- 6-174 alleles) for one year. For 3 weeks after each viral URI episode, we will monitor for the occurrence of AOM. We will compare virus type and cytokine concentrations in respiratory secretions from children who do and who do not develop AOM as a complication. Risk for AOM development will be evaluated for association with cytokine genotypes. The study will help clarify the role of specific respiratory viruses, proinflammatory cytokines, and their gene regulation in the pathogenetic mechanisms of virus-induced AOM.