Immune Mechanisms of Middle Ear Disease

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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.