Otitis media: treatment with intranasal aerosolized surfactant.
OBJECTIVE
The objective was to determine the effect of intranasal surfactant alone and with other medications administered by metered dose inhaler aerosol on the function of the eustachian tube and on the resolution of experimentally induced otitis media with effusion (OME) and acute otitis media (AOM).


METHODS
Randomized, experimental, controlled animal studies.


METHODS
Previously unreported (experiment 4) as well as published (experiments 1-3) data were detailed so that the reader could understand the continuum of information leading to the conclusions. In experiment 1, after a live-animal technique of measuring eustachian tube passive opening pressure was developed and validated, eustachian tube passive opening pressure was determined in 61 adult gerbils and 34 mice at baseline and 5 and 10 minutes after delivery of aerosolized intranasal metered dose inhaler surfactant. In experiments 2 and 3 (Klebsiella pneumoniae), lipopolysaccharide-induced OME was developed in gerbils. Thirty-five animals were randomly assigned to control, placebo, surfactant, surfactant with betamethasone, and surfactant with phenylephrine groups. Seventy animals were randomly assigned to control, placebo once daily (QD) and twice daily (BID), surfactant QD and BID, surfactant with betamethasone QD and BID, and surfactant with phenylephrine QD and BID groups. Intranasal aerosolized MDI medications were administered from postinfection day 2 until the effusion resolved. Otomicroscopy and tympanometry were performed on alternate days for 30 days. In experiment 4, AOM was developed in 39 chinchillas via transbullar injection of nontypeable Haemophilus influenzae on day 1. Thirteen animals each received placebo BID or surfactant BID, beginning on day 1. Thirteen animals received surfactant BID beginning on day 3. All administrations were continued for 10 days. Examinations were performed on seven occasions until day 27. Appropriate statistical measurements were employed, including one- and two-way ANOVA, strength-of-association measure (omega) calculation, chi, and Newman-Keuls post hoc multiple comparison tests. Significance was set as P value of less than.05.


RESULTS
In experiment 1, a significant reduction in passive opening pressure was seen in both 5- and 10-minute postsurfactant measurements. Propellant alone was not effective. In experiments 2 and 3, OME resolved after an average period of 16 to 16.5 days in control, placebo QD and BID, and surfactant with phenylephrine QD groups. A significant decrease in OME days was seen in the surfactant QD (10.57 d) and BID (8.57 d), and surfactant with betamethasone QD (8.57 d) and BID (6.3 d) groups. A significant increase was seen in the phenylephrine BID group (18.67 d). In experiment 4, tympanometry was normal or near-normal in 62% and 48% of treated ears and in only 24% of placebo ears on day 12. Sixty-seven percent of placebo ears were culture positive at day 27, compared with 10% and 16% in surfactant groups 1 and 2. Seventy-five percent of untreated animals developed severe labyrinthitis, compared with 15% in groups 1 and 2. On day 27, 58% of placebo group middle ears had fluid, whereas 61% and 62% of ears in groups 1 and 2, respectively, were dry. These findings were significant.


CONCLUSIONS
Intranasal application of aerosolized metered dose inhaler surfactant alone or with steroid reduced eustachian tube passive opening pressure in normal animals and duration of effusion in animals with experimental OME. Intranasal surfactant reduced the severity and duration of middle ear infection in AOM in this animal model.
Chandrasekhar
Sujana S
SS
Department of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA. Sujana.Chandrasekhar@mssm.edu
Mautone
Alan J
AJ
D000208:Acute Disease; D000281:Administration, Intranasal; D000336:Aerosols; D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005849:Gerbillinae; D008297:Male; D051379:Mice; D009330:Nebulizers and Vaporizers; D010033:Otitis Media / Q000188:drug therapy*; D010034:Otitis Media with Effusion / Q000188:drug therapy; D011312:Pressure; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000336:Aerosols; D013501:Surface-Active Agents