No abstract

Past studies showed that experimental rhinovirus colds in adults resulted in eustachian tube dysfunction and abnormal middle ear pressures. In the present study, the symptoms and pathophysiologic findings accompanying experimental influenza viral infection were documented. A total of 33 healthy adult volunteers were intranasally challenged with an influenza A/Kawasaki/86 (H1N1) virus and cloistered over a 9-day postchallenge period to monitor for evidence of infection, signs and symptoms of illness, and the extent and frequency of pathophysiologic responses of the nose, eustachian tube, and middle ear. Results showed a protective effect of high (> or = 16) prechallenge specific hemagglutination-inhibition antibody titer on the rate of infection and the magnitude and extent of provoked symptoms and pathophysiologic findings. Infected subjects with low (< 16) prechallenge serum antibody titers (n = 21) developed significant respiratory illness. These subjects also had objectively measurable increases in nasal secretion production, and decreased nasal patency and mucociliary clearance rates. More than 80% of the infected subjects developed eustachian tube dysfunction, and approximately 80% had middle ear underpressures of less than -100 mm H2O on study days 4 and 5. Five of 21 infected subjects with low prechallenge antibody titers had otoscopic evidence of otitis media with effusion. These results support a causal role for viral upper respiratory tract infection in the pathogenesis of otitis media, possibly mediated by the early development of eustachian tube dysfunction and abnormal middle ear pressure.

In this study, magnetic resonance imaging (MRI) was used to define in vivo the effect of experimental functional obstruction of the eustachian tube (ET) on vascular permeability and the development of middle ear (ME) effusion. After collection of baseline data for ME pressure and MRI, the right tensor veli palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to induce ET obstruction. The left tensor veli palatini muscle was injected with saline in 4 monkeys. Right and left ME pressures and compliances were measured twice daily over a follow-up period of 36 days, and MRI scanning sessions including administration of a contrast agent, gadopentetate dimeglumine, were repeated on days 3, 6, 11, 15, 21, 29, and 36 in 6 animals and on days 15, 21, 29, and 36 in 4 animals. Two right ears did not develop underpressures, 5 developed persistent underpressures, and 3 developed underpressures that resolved. No changes in MRI parameters were noted for the ears that did not develop underpressures, but a progressive brightening of the ME on T2-weighted images, indicative of the development of inflammation and effusion, was noted for the others. Also, an increasing rate of transfer of the contrast agent between the vascular and ME compartments, indicative of increasing vascular permeability, was observed to track the temporal changes in ME pressure. These results support a causal relationship between ET dysfunction, ME underpressures, increased vascular permeability, and otitis media with effusion

To better understand the significance of viral upper respiratory tract infections in the pathogenesis of acute otitis media (OM), 27 adults underwent intranasal inoculation with influenza A virus. Monitoring consisted of antibody titer determination, tympanometry, and otoscopy. Microbiologic analysis consisted of cultures and polymerase chain reaction (PCR)-based detection for influenza A virus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All subjects became infected with the challenge virus. By day 4, 16 (59%) developed middle ear pressures of -100 mm H2O or below and 4 (25%) of them developed OM. One subject (4%) developed purulent OM requiring myringotomy for pain relief. Middle ear effusion cultures were negative. PCR analysis of that subject's middle ear effusion and nasal washes were positive for influenza A virus and S. pneumoniae. These findings support a causal role for viral upper respiratory tract infections in the pathogenesis of OM, possibly mediated by middle ear underpressures and viral and bacterial middle ear infection.