Immune Mechanisms of Middle Ear Disease

超出提供的空间。中耳炎(OM)是儿童最常见的疾病之一。尽管社会支出巨大，但很少有有效的治疗方法，因此，密集研究的重点是疾病预防领域。病毒性上呼吸道感染(VURI)是OM发生的一个明确的前提条件，通过接种疫苗或免疫球蛋白治疗预防VURI可以降低OM的人群患病率。然而，这些治疗方法风险高、费用高，对于非针对性地应用于一般婴儿和儿童人群来说无效。由于OM发生在大约25%的VURI中，并且只发生在一小部分儿童中，因此特别识别那些在VURI期间发生OM的高危人群(根据病史、基因或表型)将显著减少过度治疗的程度(即治疗风险很小的VURI引起OM的患者)。根据OM病史可以将儿童分为不同的风险类别，双胞胎研究表明，OM的易感性具有很高的遗传成分。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URI期间合成和释放；这些细胞因子与疾病的表达相关，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，我们报告了自然感染RSV的婴儿中干扰素-y启动子基因与OM发生率之间的关系，以及婴儿和成人中感染RSV的IL-6启动子基因与疾病体征之间的关系。我们提出了一项前瞻性研究，对象是18个月至3岁的幼儿，在经历典型的RSV感染和OM的“季节”之后。所有登记的患者都将接受一组细胞因子反应基因的基因分型，并将确定细胞因子基因对感染、疾病评分/感染和OM/感染的影响。主要的假设是，细胞因子基因型别可以预测疾病的表现和幼儿呼吸道合胞病毒感染期间OM的发生率。表演网站========================================Section End===========================================

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===========================================