Alpha1-antitrypsin single dose adjuvant therapy for acute otitis media.

Abstract

Proteases have been shown to play a role in the pathogenesis of otitis media. Inhibition of these proteases can improve treatment outcomes in certain conditions. The goal of this study was to determine if intratympanic administration of a single dose of the protease inhibitor, recombinant alpha 1-antitrypsin (rAAT), can facilitate resolution of acute otitis media (AOM) in the chinchilla. Pneumococcus was injected into both middle ears of 12 chinchillas. After 3 to 4 days, middle ears were cultured, systemic antibiotics were initiated, and rAAT or its vehicle was administered into the middle ears of all animals. Serial tympanic membrane (TM) scoring, tympanometry, and auditory-evoked brain stem response testing were performed. Animals were sacrificed at varying timepoints and temporal bones studied for objective measures of OM. Although not reaching statistical significance, there was a trend to more rapid resolution of AOM in rAAT-treated ears. Tympanometry, auditory thresholds, and quantitative histologic parameters did not differ between rAAT and vehicle treated ears. A single dose of intratympanic rAAT likely does not facilitate the resolution of antibiotic-treated pneumococcal AOM in the chinchilla model. Serial administration of this protease inhibitor may be necessary to see a significant treatment effect.