Role of Virus and Genetic Susceptibility in Otitis Media

描述(申请人提供)：中耳炎(OM)是婴幼儿的常见病。虽然美国每年花费30到50亿美元来管理这种疾病，但很少有治疗方法被认为是有效的。有证据表明，OM的直接原因是先前或并发的病毒性上呼吸道感染(VURI)，有人建议，大多数OM的发作可以通过预防VURI或在感染之前及早治疗来预防。近年来，有效的疫苗和抗病毒药物已经上市，可以预防或治疗某些引起OM的病毒的感染，其他病毒正在开发中。然而，是否明智地引入这些可能的OM干预措施取决于一些目前尚不清楚的因素。对于每一种可能导致vURI的病毒，这些因素包括：OM的自然病史、与vURI和OM呈现相关的时间模式、OM和vURI的共同发生率以及vURI和OM有症状的发作的百分比等。此外，为了避免对风险较小的OM患者进行过度治疗，定义易患OM的患者特征也很重要。在拟议的研究中，我们将获得这些信息。具体地说，我们将在典型的感冒月份通过每日症状记录和中耳状况评估、每周耳朵和鼻子检查以及每月细菌和病毒检测来研究幼儿；如果他们出现感冒样疾病或OM的迹象和症状，我们将在诊所重新评估这些儿童，以确定他们是否患有OM、vURI和病原体病毒。对于所有登记的儿童，我们将确定他们产生某些细胞因子的基因，这些细胞因子被认为在vURI和/或OM的发展过程中影响疾病的表达。在VURI期间，我们还将确定鼻子中产生的细胞因子的类型，并将这些与OM的发生率联系起来。通过对儿童OM和VURI的密切随访，我们将估计所需的参数，以确定预防VURI引起的OM的不同策略的预期效果和效率。作为vURI的并发症，细胞因子基因型别和表达模式在易患OM的发展中的作用可能为靶向干预提供可能的“高危”人群。这些结果将用于未来通过调节vURI发病机制来预防OM的研究设计。

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.