Alpha1-antitrypsin single dose adjuvant therapy for acute otitis media

Otolaryngol Head Neck Surg. 2006 Jul;135(1):111-5. doi: 10.1016/j.otohns.2005.11.050.

Abstract

Objectives: 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.

Methods and measures: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Auditory Threshold
  • Chinchilla
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Otitis Media / drug therapy*
  • Otitis Media / microbiology
  • Otitis Media / physiopathology
  • Pneumococcal Infections / drug therapy
  • Pneumococcal Infections / microbiology
  • Streptococcus pneumoniae / pathogenicity
  • Treatment Outcome
  • Trypsin Inhibitors / administration & dosage
  • Trypsin Inhibitors / therapeutic use*
  • alpha 1-Antitrypsin / administration & dosage
  • alpha 1-Antitrypsin / therapeutic use*

Substances

  • Trypsin Inhibitors
  • alpha 1-Antitrypsin