Alpha1-antitrypsin single dose adjuvant therapy for acute otitis media.
OBJECTIVE
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
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.
Antonelli
Patrick J
PJ
Department of Otolaryngology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. antonpj@ent.ufl.edu
Schultz
Gregory S
GS
Sundin
David J
DJ
Pemberton
Philip A
PA
Barr
Philip J
PJ
D000208:Acute Disease; D000818:Animals; D001309:Auditory Threshold; D002682:Chinchilla; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D016896:Treatment Outcome; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000627:therapeutic use*
D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin