IMMUNE MECHANISMS OF MIDDLE EAR DISEASE

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DESCRIPTION: Otitis media is a very common disease of children frequently diagnosed during upper respiratory infection. Surveys suggest that chronic otitis media is more common in children with allergies. The applicant's studies of twins from birth have reportedly found positive allergy skin tests in 50% of twins with chronic otitis media with effusion contrasted with 20% of twins with no ear disease (p<0.02). Past studies in allergic patients by this investigator and his group showed that nasal inflammation provoked by intranasal allergen challenge or natural pollen exposure is associated with eustachian tube obstruction, a risk factor for otitis media. Other studies by this group demonstrated that experimental upper respiratory infection in adult subjects using rhinovirus and influenza virus caused eustachian tube obstruction, abnormal middle ear pressures and otitis media. These viral upper respiratory infections also caused changes in bacterial flora of the nasopharynx, altered neutrophil function and depressed certain aspects of immune function. In addition, increased IgE responses of these subjects were found during and after the viral upper respiratory infections suggesting that a unique response of allergic subjects to virus infections may contribute to their higher incidence of otitis media. This work described in the present proposal is intended to further define various aspects of the interactions between allergy and virus infection and evaluate mechanisms which contribute to otitis media. Plans are also described to study respiratory syncytial virus (RSV) experimental infection and evaluate mechanisms which contribute to otitis media. This collaborative research effort by immunologists, otolaryngologists, microbiologists, physiologists and molecular biologists will better define the role of viral infection and allergy in the pathogenesis of otitis media and should result in improved management of this disease. The specific aims of the investigators in the current proposal are: (1) To extend the virus challenge models to include infection with RSV by: (a) defining the response of the nose, ET, and ME of AR and non-AR subjects to experimental RSV infection; (b) evaluating the potential of RSV to cause OM in adult volunteers; (c) determining the effects of RSV infection on host immune function, inflammatory mediator elaboration and nasopharyngeal bacterial carriage; and (d) evaluating the potential of RSV to prime the responses of the nose, ET, ME, and lungs to secondary challenges with inflammatory stimuli. (2) To evaluate suggested mechanisms of OM pathogenesis during experimental viral URI by (a) determining if poor ET function predisposes to OM; (b) assaying the effusions recovered from subjects with experimental OM for the presence of viruses and bacteria; (c) documenting the changes in nasopharyngeal flora during these infections; and (d) further characterizing the effects of virus infection on host defenses. (3) To evaluate the hypothesis that the presence of nasal allergy is a significant risk factor for the development of OM secondary to viral URIs by (a) comparing the responses of AR and non-AR subjects to viral infection; (b) determining if the response of AR subjects is primed by preexisting and concurrent allergen exposure to a perennial allergen; and (c) determining if a viral URI exacerbates the symptoms and pathophysiologies provoked by nasal challenge with a perennial allergen.