Immune Mechanisms of Middle Ear Disease

中耳疾病的免疫机制

• 批准号: 6615942
• 负责人: DAVID P SKONER
• 金额: $ 11.25万
• 依托单位: ALLEGHENY-SINGER RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-08-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6615942
• 关键词: clinical research; cytokine; disease /disorder etiology; disease /disorder proneness /risk; epidemiology; gene environment interaction; genetic susceptibility; genotype; human subject; immunogenetics; interleukin 6; otitis media; preschool child (1-5); prognosis; respiratory infections; stress

DESCRIPTION (provided by applicant): Otitis media (OM) is one of the most common diseases in children. Despite large societal expenditures, few treatments are efficacious and, consequently, a focus of intensive research is in the area of disease prevention. Viral upper respiratory infection (vURI) is a well-defined precondition for the development of OM and prevention of vURI by vaccination or immunoglobulin therapies was shown to reduce the population prevalence of OM. However, those treatments are risky and expensive rendering them ineffective for non-targeted application to the general population of infants and children. Because OM occurs in approximately 25% of vURIs and in only a subset of children, the ad hoc identification of those persons at "high risk" (by history, genotype, or phenotype) for OM during vURIs would significantly reduce the extent of over-treatment (i.e. treatment of patients with little risk of OM caused by vURI). Children can be classified by OM history into different risk categories and twin studies showed that susceptibility to OM has a high heritable component. We hypothesize that one component of OM heritability is the type of host response to a vURI. In earlier studies, we showed that: cytokines are synthesized and released during URIs; these cytokines correlate with illness expression, and cytokine production is modulated by genetic and environmental factors. In pilot studies, we reported a relationship between the interferon-? promoter genotype and OM incidence in infants with natural RSV infection and between an IL-6 promoter genotype and signs of illness in infants and adults with RSV infection. We propose a prospective study of young children, aged 18 months to 3 years followed through the typical RSV "season" for RSV infection and OM. All enrolled patients will be genotyped for a panel of cytokine response genes, and the influence of cytokine genotype on infection, illness scores/infection and OM/infection will be determined. The primary hypothesis is that cytokine genotype is predictive of illness expression and of OM incidence during a documented RSV infection in young children.

描述（申请人提供）：中耳炎是儿童最常见的疾病之一。尽管社会支出巨大，但有效的治疗方法很少，因此，疾病预防领域是深入研究的重点。病毒性上呼吸道感染（vURI）是OM发展的一个明确的先决条件，通过疫苗接种或免疫球蛋白治疗预防vURI被证明可以降低OM的人群患病率。然而，这些治疗方法有风险且费用昂贵，使得它们对一般婴儿和儿童的非靶向应用无效。由于大约25%的vURI患者会发生OM，而且仅在一小部分儿童中发生，因此在vURI期间对OM“高风险”人群（根据病史、基因型或表型）进行特别鉴定将大大减少过度治疗的程度（即对由vURI引起的OM风险很小的患者进行治疗）。儿童可根据骨髓瘤病史分为不同的风险类别，双胞胎研究表明，对骨髓瘤的易感性具有很高的遗传成分。我们假设OM遗传度的一个组成部分是宿主对vURI的响应类型。在早期的研究中，我们发现：细胞因子在uri过程中被合成和释放；这些细胞因子与疾病表达相关，细胞因子的产生受遗传和环境因素的调节。在初步研究中，我们报道了干扰素-？启动子基因型与自然RSV感染婴儿的OM发病率以及IL-6启动子基因型与RSV感染婴儿和成人疾病体征之间的关系。我们建议对18个月至3岁的幼儿进行前瞻性研究，随访典型的RSV感染和OM的RSV“季节”。所有入组的患者将对一组细胞因子反应基因进行基因分型，并确定细胞因子基因型对感染、疾病评分/感染和OM/感染的影响。主要的假设是，细胞因子基因型可以预测幼儿呼吸道合胞病毒感染期间的疾病表达和OM发病率。