Despite the availability for effective antibiotics for treatment of acute otitis media (AOM), treatment failures, persistent effusions and recurrences are common. One factor associated with poor treatment outcome is concurrent viral infection, which we have shown to be associated with increased levels of inflammatory mediators in the middle ear (ME) fluids. We propose that inflammatory mediators, particularly histamine and leukotrienes, play a significant role in both the pathogenesis of and recovery from AOM, and therefore will test whether adjuvant therapy aimed at counteracting histamine actions (antihistamine), and/or inhibiting formation of leukotrienes and other inflammatory substances (corticosteroid), in addition to antibiotic, will improve acute and long- term outcome of AOM by reducing the degree of the initial inflammation. The efficacy of the adjuvant drugs will be tested in 2 separate, simultaneous studies which use a randomized, double-blind, placebo- controlled design over a 4-year period. In Study 1, 60 patients will be enrolled at the onset of AOM. Tympanocentesis will be performed prior to and 5 days into therapy to measure histamine and leukotriene levels and document bacterial and viral etiology. These patients will be followed for the duration of ME effusion. Groups will be compared for bacteriologic and virologic etiology, changes in ME histamine and leukotriene levels, and clinical outcomes. Study 2 is a large clinical trial of 2000 children, enrolled under 1 year of age with 2 documented prior episodes of OM but not present ME effusion. They will be followed by home visits with tympanometry and telephone contacts until their next acute episode, and the assigned to treatment groups. Results of treatment will be compared among groups for rate of treatment failure, duration of effusion, and recurrences of OM over 9 mo. Response to therapy will also be related to OM risk factors, severity of symptoms at diagnosis, and evidence of concurrent viral infection of the respiratory tract. These studies should clarify the potential benefits of antihistamine and/or corticosteroid therapy, both for treatment of acute and possible prevention of recurrent and/or chronic OM in infants, and shed light on associations between adjuvant treatment, viral infection, inflammatory mediators. If the drugs are proven efficacious, their use would make a significant impact on health care. If they are inefficacious, discontinuation of their use will reduce costs and inconvenience to parents.
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