The objectives of this research are to define those immune mechanisms including allergy which have been suggested but not established as important in the pathogenesis of otitis media with effusion (OME). OME is a multifactorial syndrome in which infection and eustachian tube obstruction (ETO) are the best documented pathogenetic mechanisms. A provocative intranasal antigen (pollen) challenge which induces ETO in adults with allergic rhinitis has been shown to be a reproducible, reversible immune response which is antigen dose dependent and related to IgE antibody. This research plan will study immune and non-immune factors which may sustain and prolong ETO and explore potential relationships for antigen induced ETO and upper respiratory infections. Since OME is a disease primarily of children, this research plan will begin to extend these observations from adults to children with allergic rhinitis and OME. Immune reactions, including allergy, release and generate mediators in tissues and secretions of inflammation. This research will study whether intranasal provocative challenge with these mediators including histamine, prostaglandins and leukotrienes as well as methacholine will induce ETO. New technology including a sonometric method of measuring ETO along with a computer assisted rhinomanometer with capabilities of performing both active and passive, anterior and posterior rhinometry will be utilized. In addition, the presence of these mediators will be studied in middle ear fluids, and nasal secretions of patients with OME and allergic rhinitis and correlated with presence of Ig isotypes, bacteria cultures and clinical course. Since certain questions concerning the development of ETO and OME require invasive techniques and are not suitable in man, a monkey animal model of antigen induced ETO has been developed. Histamine intranasal challenge has also induced ETO in the monkey, especially in younger animals and the role of histamine, methacholine, prostaglandins and leukotrienes in the pathogenesis of ETO and OME will be examined in this model. Age related differences will be explored at each aspect of the experimental design. By understanding the role of immune reactions, especially allergy, in the pathogenesis of ETO and OME, this research should provide the basis for future studies to establish better diagnosis and therapy of this most common pediatric illness.
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