Immune Mechanisms of Middle Ear Disease

超出所提供的空间。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，深入研究的重点是疾病预防领域。病毒性上呼吸道感染（vURI）是发生OM的明确前提条件，通过疫苗接种或免疫球蛋白治疗预防vURI可降低OM的人群患病率。然而，这些治疗是有风险的和昂贵的，使得它们对于非靶向应用于婴儿和儿童的一般群体无效。由于OM发生在约25%的vURI中，并且仅发生在儿童的一个子集中，因此特别确定那些具有使用vURI的OM“高风险”（通过病史、基因型或表型）的人将显著降低过度治疗的程度（即治疗vURI引起OM风险很小的患者）。儿童可以根据OM病史分为不同的风险类别，双胞胎研究表明，OM的易感性具有较高的遗传性。我们假设OM遗传性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URIs期间合成和释放;这些细胞因子与疾病表达相关，并且细胞因子的产生受到遗传和环境因素的调节。在初步研究中，我们报道了干扰素-γ启动子基因型与自然RSV感染婴儿OM发病率之间的关系，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岁的幼儿进行一项前瞻性研究，随后进行RSV感染和OM的典型RSV“季节”。将对所有入组患者进行一组细胞因子应答基因的基因分型，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。主要假设是，细胞因子基因型是疾病的表达和OM的发病率在记录的RSV感染的幼儿预测。性能现场=

EXCEED THE SPACE PROVIDED. 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 iduring 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 ihypothesize 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-y 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. PERFORMANCE SITE ========================================Section End===========================================