Role of Virus and Genetic Susceptibility in Otitis Media

描述（由申请人提供）：中耳炎（OM）是婴儿和儿童的常见疾病。虽然美国每年花费30亿至50亿美元用于治疗这种疾病，但很少有治疗方法被认为是有效的。充分支持的OM的直接原因是先前或并发的病毒性上呼吸道感染（vURI），并且已经表明，大多数OM发作可以通过预防vURI或通过先前对这些感染进行早期治疗来预防。近年来，有效的疫苗和抗病毒药物已上市，可预防或治疗引起OM的一些病毒感染，其他疫苗和抗病毒药物正在开发中。然而，明智地引入这些可能的干预措施，OM取决于一些目前未知的因素。这些包括，对于每种可能导致vURI的病毒：OM的自然史，与vURI和OM表现相关的时间模式，OM和vURI的同时发生率以及有症状的vURI和OM发作的百分比等。此外，为了避免过度治疗OM风险很小的患者，定义易患OM的患者特征很重要。在拟议的研究中，我们将获得这些信息。具体来说，我们将研究幼儿在他们的家庭环境中在整个典型的感冒流感月份，每天记录症状和评估中耳状态，每周耳鼻检查和每月细菌和病毒检测;如果他们发展的迹象和症状的感冒样疾病或OM，我们将重新评估这些儿童在诊所的OM，vURI和病原病毒的确诊。对于所有入选的儿童，我们将确定他们产生某些细胞因子的基因型，这些细胞因子被认为会影响vURI和/或OM发展期间的疾病表达。在vURI期间，我们还将确定鼻内产生的细胞因子类型，并将其与OM发病率联系起来。通过对OM和vURI儿童的密切随访，我们将估计确定不同策略预防vURI引起的OM的预期疗效和效率所需的参数。细胞因子基因型和表达模式在诱发OM发展为vURI并发症中的作用可能为靶向干预描绘出可能的“高危”人群。这些结果将被用于设计未来的研究，预防OM的缓和vURI发病机制。

DESCRIPTION (provided by applicant): Otitis media (OM) is a common disease in infants and children. While each year between 3 and 5 billion dollars are spent in the United States on the management of this disease, few treatments are recognized as effective. The well-supported immediate cause of OM is a preceding or concurrent viral upper respiratory tract infection (vURI) and it has been suggested that most episodes of OM could be prevented by preventing vURIs or by early treatment of those infections prior. In recent years, effective vaccines and antivirals have been marketed that prevent or treat infection with some of the viruses that cause OM, and others are in development. However, the judicious introduction of these possible interventions for OM depends on a number of factors not known at present. These include, for each virus that can cause vURIs: the natural history of OM, the temporal pattern relating vURIs and OM presentations, the co-incidence of OM and vURI and the percent of vURI and OM episodes that are symptomatic, among others. Also, to avoid over-treatment of patients at little risk for OM, a definition of patient characteristics that predispose to OM is important. In the proposed study, we will acquire this information. Specifically, we will study young children in their home environment throughout the typical cold-flu months by daily symptom recording and assessment of middle ear status, weekly ear and nose examinations and monthly bacterial and virus assays; and, if they develop signs and symptoms of either a cold-like illness or OM, we will re-evaluate these children in the clinic for confirmatory diagnosis of OM, vURI and etiological virus. For all enrolled children, we will determine their genotype for the production of certain cytokines that were suggested to influence disease expression during a vURI and/or the development of OM. During vURIs, we will also determine the types of cytokines that are produced in the nose, and relate these to OM incidence. From this close follow up of children for OM and vURI, we will estimate the parameters needed to define the expected efficacy and efficiency of different strategies to prevent OM caused by vURI. The role of cytokine genotype and expression pattern in predisposing to the development of OM as a complication of vURI may delineate possible "at risk" groups for targeted intervention. These results will be used in the design of future studies that prevent OM by moderating vURI pathogenesis.