Role of Virus and Genetic Susceptibility in Otitis Media

描述（申请人提供）：中耳炎（Otitis media， OM）是婴幼儿常见病。虽然美国每年在治疗这种疾病上花费30亿到50亿美元，但很少有治疗方法被认为是有效的。有充分证据支持OM的直接原因是先前或并发的病毒性上呼吸道感染（vURI），并且已经建议通过预防vURI或早期治疗这些感染来预防大多数OM发作。近年来，有效的疫苗和抗病毒药物已经上市，用于预防或治疗引起OM的某些病毒感染，其他疫苗和抗病毒药物正在开发中。然而，是否明智地采用这些可能的干预措施，取决于目前尚不清楚的一些因素。这些包括，对于每一种可引起vURI的病毒：OM的自然史、vURI和OM表现相关的时间模式、OM和vURI的合并发病率以及vURI和OM症状发作的百分比等。此外，为了避免对风险很小的OM患者进行过度治疗，确定易患OM的患者特征是很重要的。在拟议的研究中，我们将获得这些信息。具体来说，我们将在典型的感冒流感月份对儿童的家庭环境进行研究，每天记录症状，评估中耳状况，每周进行耳鼻检查，每月进行细菌和病毒检测；如果他们出现感冒样疾病或OM的体征和症状，我们将在诊所对这些儿童进行重新评估，以确定OM、vURI和病原学病毒的确诊。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的发展过程中的疾病表达。在vuri期间，我们还将确定鼻子中产生的细胞因子类型，并将其与OM发病率联系起来。通过对儿童OM和vURI的密切随访，我们将估计出定义预防由vURI引起的OM的不同策略的预期功效和效率所需的参数。细胞因子基因型和表达模式在作为vURI并发症的OM易感性中的作用可能会描述可能的“高危”人群进行针对性干预。这些结果将用于通过调节vURI发病机制来预防OM的未来研究设计。

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.