Role of Virus and Genetic Susceptibility in Otitis Media

病毒和遗传易感性在中耳炎中的作用

• 批准号: 6576304
• 负责人: Cuneyt Metin Alper
• 金额: $ 50.1万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6576304
• 关键词: clinical research; cytokine; disease /disorder etiology; disease /disorder prevention /control; family genetics; genetic susceptibility; human genetic material tag; human subject; inflammation; otitis media; pathologic process; preschool child (1-5); respiratory infections; virus diseases

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.

描述（申请人提供）： 中耳炎（OM）是婴儿和儿童的常见疾病。尽管美国每年花费 3 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。得到充分支持的 OM 直接原因是先前或并发的病毒性上呼吸道感染 (vURI)，并且有人建议，大多数 OM 发作可以通过预防 vURI 或早期治疗这些感染来预防。近年来，有效的疫苗和抗病毒药物已上市，可预防或治疗某些导致 OM 的病毒感染，其他病毒正在开发中。然而，明智地引入这些可能的 OM 干预措施取决于许多目前未知的因素。对于每种可能导致 vURI 的病毒，这些因素包括：OM 的自然史、vURI 和 OM 表现相关的时间模式、OM 和 vURI 的一致性以及有症状的 vURI 和 OM 发作的百分比等。此外，为了避免对 OM 风险较小的患者进行过度治疗，定义易患 OM 的患者特征也很重要。在拟议的研究中，我们将获取这些信息。具体来说，我们将通过每日症状记录和中耳状态评估、每周耳鼻检查以及每月细菌和病毒检测，在整个典型感冒流感月份的家庭环境中研究幼儿；并且，如果他们出现类似感冒或 OM 的体征和症状，我们将在诊所重新评估这些儿童，以确认 OM、vURI 和病原病毒的诊断。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，我们还将确定鼻子中产生的细胞因子的类型，并将其与 OM 发生率联系起来。通过对儿童 OM 和 vURI 的密切跟踪，我们将估计定义不同策略的预期功效和效率所需的参数，以防止 vURI 引起的 OM。细胞因子基因型和表达模式在导致 OM 作为 vURI 并发症的发展过程中的作用可能会描绘出可能的“高危”群体，以进行有针对性的干预。这些结果将用于设计未来的研究，通过调节 vURI 发病机制来预防 OM。