The goals of this research are to define the etiologies and pathogeneses of otitis media with effusion. Our past studies have documented several pathogenic pathways whereby nasal inflammation provoked by allergy or viral infection are manifest as eustachian tube obstruction, a recognized cause of otitis media with effusion. The purpose of this ongoing research is to define the role and interaction of allergy and viral infection in promoting nasal congestion, tubal obstruction and middle ear pathophysiology. These relationships will be explored with an emphasis on amplification, modulation and prolongation of primary responses. Specifically, we will utilize human models for challenges with inflammatory mediators, allergens and viruses, and animal models of IgE hypersensitivity to: 1) define the role of inflammatory mediators in causing tubal obstruction and middle ear disease; 2) document the potential of allergen and viral priming and late allergic reactions to enhance and sustain the nasal and middle ear pathophysiologies; and 3) determine if allergic rhinitis subjects are hyperresponsive to upper respiratory virus infection. Age related response differences between children and adults will be further defined. Children who are indentified in prospective studies as "otitis prone" will be evaluated for immune defects to explain their recurrent ear infections. Middle ear effusions (MEE) from children with acute and chronic OME will be assayed for histamine, prostaglandins, tryptase and eosinophil derived major basic protein and neurotoxin. Enhanced basophil histamine release and production of histamine releasing factors will be explored as possible predisposing factors in these children. This collaborative research effort by clinical immunologists, otolaryngologists, microbiologists, physiologists and biochemists will better define the role of allergy and viral infection in the pathogenesis of OME and should result in improved diagnosis and management of this most common pediatric disease.