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（由申请人提供）：中耳炎（OM）是婴儿和儿童的常见疾病。尽管每年在美国花费了3至50亿美元的这种疾病管理，但很少有治疗被认为有效。 OM的良好支持的直接原因是先前或并发的病毒上呼吸道感染（VURI），并且已经提出，可以通过预防Vuris或通过早期治疗这些感染来预防OM发作。近年来，已经销售有效的疫苗和抗病毒药，可预防或治疗引起OM的某些病毒，而其他病毒正在开发中。但是，明智地引入了对OM的干预措施取决于目前尚不知道的许多因素。这些包括可能引起Vuris的每种病毒：OM的自然历史，与Vuris和OM演示有关的时间模式，OM和Vuri的共同存在以及Vuri和Om发作的百分比等有症状的。同样，为了避免过度治疗OM风险的过度，对OM易感的患者特征的定义很重要。在拟议的研究中，我们将获取此信息。具体来说，我们将通过每天记录和评估中耳状态，每周的耳朵和鼻子检查以及每月的细菌和病毒测定法，在整个典型的冷FLU月中研究幼儿在家庭环境中。而且，如果他们出现疾病或OM的体征和症状，我们将在诊所重新评估这些儿童，以确认对OM，Vuri和病因病毒的诊断。对于所有入学的儿童，我们将确定其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发展过程中的疾病表达。在Vuris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。从对OM和Vuri的儿童的紧密随访中，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OM发展中作为Vuri并发症的发展可能会描绘出有针对性干预的“危险”组。这些结果将用于通过调节Vuri发病机理来预防OM的未来研究的设计。