Otitis media with effusion: disease or defense? A review of the literature.

Many studies of otitis media with effusion (OME) have been published, most of them dealing with risk factors. The literature correlates this condition with various patient characteristics and socio-economic factors, but none of these have been identified as the sole causative factor. A review of the literature suggests that otitis media with effusion is a response to pathogenic bacteria and thus a normal protective reaction of the body. Therefore, the decision on whether or not treatment is indicated should take the natural course of that response into account. In light of the literature reviewed here, we conclude that there is usually no need to treat middle ear effusion in young children.

Lipopolysaccharide concentration and bone resorption in cholesteatoma.

HYPOTHESIS: There is a relationship between the local lipopolysaccharide (LPS) concentration in cholesteatoma and local bone resorption in chronic otitis media (COM) with cholesteatoma. BACKGROUND: During the past decade, it has become known that the recruitment of osteoclasts is the main causative factor that induces bone destruction in COM with cholesteatoma. Cellular inflammation factors like cytokines may trigger the osteoclast. Sequel to this, LPS is able to up-regulate cytokines. This makes it of interest to study whether the local LPS concentration is related to bone resorption in cholesteatoma. MATERIALS AND METHODS: Twenty-four cholesteatoma samples and control tissue from COM patients without cholesteatoma were collected. During surgery, the degree of bone resorption was established and classified. Retrospectively, the authors checked whether patients had chronic purulent otorrhea. LPS concentration of the tissue samples was measured by the limulus amebocyte lysate test. The one-way analysis of variance test was used to determine the relation between LPS concentration, otorrhea, and local bone resorption. RESULTS: A significantly higher concentration of LPS was measured in samples from patients with cholesteatoma with bone resorption and otorrhea compared with cholesteatoma without bone resorption and control tissue. There were no significant differences between the LPS levels of the different groups of patients with bone resorption. CONCLUSION: It is suggested that LPS is one of the first factors in the cascade of bone resorption in COM with cholesteatoma.

The importance of human cochlear anatomy for the results of modiolus-hugging multichannel cochlear implants.

HYPOTHESIS: The fact that the anatomy of the basal turn of the human cochlea, especially, is essentially different from that of other species is likely to influence the outcome of cochlear implantation. BACKGROUND: Multichannel cochlear implants give better speech understanding than single-channel devices. They are intended to make use of the tonotopic organization of the cochlea by selectively stimulating subpopulations of the auditory nerve. At higher stimulus levels and with monopolar stimulation, excitation of nerve fibers from other turns may interfere with this concept, especially with modiolus-hugging electrodes. METHODS: A three-dimensional spiraling computer model of the human cochlea, based on histologic data, was used to test the spatial selectivity and the dynamic range before cross-turn stimulation takes place for the Clarion HiFocus implant with and without a positioner. The results were compared with a similar model of the guinea pig cochlea. RESULTS: In humans (in contrast to the guinea pig), a well-designed modiolus-hugging electrode yielded reduced current thresholds and high spatial selectivity without reduction of the useful dynamic range. The apical turn of the human cochlea, however, is largely comparable in this respect with the guinea pig cochlea, where cross-turn stimulation reduces the dynamic range substantially. CONCLUSION: The clinical success of cochlear implantation in humans and the favorable results with modiolus-hugging devices depend on the anatomy of the human cochlea.

Efficacy of bactericidal/permeability-increasing protein in experimental otitis media with effusion in rats: a new therapy for mucosal infections.

Otitis media with effusion (OME) is characterized by the presence of fluid in the middle ear without signs or symptoms of acute infection and by persistent changes in the middle ear mucosa. These are mainly induced by gram-negative bacterial infection and dysfunction of the eustachian tube (ET). Gram-negative bacteria (GNB) contain lipopolysaccharide (LPS) in their outer membrane that is responsible for inflammatory reactions in the middle ear. In this study we investigated the therapeutic effect of a recombinant LPS-binding protein, bactericidal/permeability-increasing protein (rBPI21), on the repair of mucosal damage in rats with experimentally induced OME. OME was induced by obstruction of the eustachian tube in combination with LPS injection. Twelve weeks after OME induction, secretory cells in the tympanic orifice of the middle ear were increased from an average of 14 +/- 2 to 31 +/- 5, ciliated cells were decreased from 24 +/- 4 to 6 +/- 4, and the number of macrophages in the subepithelial layer increased from 13 +/- 4 to 27 +/- 3. A single dose of rBPI21 was administered directly into the middle ear cavity 2 weeks after the induction of OME. Histologic examination of the middle ear mucosa at 4 and 12 weeks after OME induction showed that mucosal changes were restored by rBPI21 treatment. These results demonstrate that the middle ear mucosa recovers from inflammatory changes associated with OME after treatment with rBPI21. This suggests that rBPI21 may be useful in the treatment of OME and of mucosal infections of the respiratory tract.

Inhibition of endotoxin effects on cultured human middle ear epithelium by bactericidal permeability-increasing protein.

HYPOTHESIS/BACKGROUND: Endotoxin can induce morphologic changes to middle ear epithelium, which can disturb the mucociliary clearance system (MCS) and lead to otitis media with effusion (OME). The bactericidal/permeability-increasing (BPI) protein is a major component of neutrophil granules and binds with high affinity to endotoxin. In this study, the capacity to inhibit the effects of endotoxin by rBPI21, a recombinant amino-terminal analog derived from BPI, was investigated on cultured human middle ear epithelium using light microscopy and scanning- and transmission electron microscopy. METHODS: Human middle ear epithelium was air-exposed cultured on a collagenous underlayer with different additions of endotoxin and rBPI21 to the culture medium. The tissue specimens were inspected after 4 weeks for the number of ciliated and secretory cells, thickness of the mucosal layer, and cell size. RESULTS: The morphologic changes induced by endotoxin were increased thickness of the mucosal layer and increased number of secretory cells. These changes were significantly diminished or even absent when endotoxin was added with rBPI21 to the culture medium. CONCLUSION: rBPI21 can inhibit morphologic changes in the middle ear epithelium due to endotoxin. Hence, the authors believe that rBPI21 can be a new therapeutic agent in the treatment of OME.

Long-term audiometric follow-up of click-evoked auditory brainstem response in hearing-impaired infants.

Conventional pure-tone thresholds were collected as determined at ages between 4 and 8 years from a group of 163 infants, tested by auditory brainstem response (ABR) in the age range between 1 and 3 years old for objective hearing assessment. The subjects suffered from a variety of degrees and types of sensorineural hearing impairment. The prognostic value of the ABR peak V thresholds in response to 0.1 ms clicks with respect to the behavioural thresholds at octave frequencies from 125 to 8,000 Hz obtained later is evaluated. Correlation between ABR and behavioural thresholds is largest in the 1,000- to 8,000-Hz frequency range. Predicted pure-tone audiograms (mean and SD) were determined for each 10-dB class of ABR thresholds. SDs are in the order of 15 to 18 dB in the 500- to 4,000-Hz range and slightly higher at adjacent frequencies (i.e., somewhat larger than in comparable adult studies). Mean pure-tone thresholds in the 1,000- to 8,000-Hz frequency range are up to 20 dB worse than ABR thresholds, which is opposite to findings in normally-hearing subjects. Thus, with an increasing degree of sensorineural hearing impairment, pure-tone thresholds increase at a significantly higher rate than ABR thresholds. The observation is explained in terms of reduced temporal integration in cochlear hearing loss. ABR thresholds worse than 80 dB nHL are demonstrated to have very limited predictive value with respect to the amount of residual hearing, not only in the low- but also in the high-frequency range. The presence of otitis media during ABR testing is shown to make estimation errors increase to more than 25 dB (SD).

Bactericidal/permeability-increasing protein prevents mucosal damage in an experimental rat model of chronic otitis media with effusion.

In this study, the efficacy of bactericidal/permeability-increasing protein (BPI) was assessed in a rat model of chronic otitis media with effusion. BPI injection prevented disturbance of the mucociliary clearance system of the middle ear. Hence, it is postulated that BPI can be a new therapy for chronic otitis media with effusion.

Endotoxin and tumor necrosis factor-alpha in middle ear effusions in relation to upper airway infection.

OBJECTIVES/HYPOTHESIS: This study was performed to elucidate the role of endotoxin and tumor necrosis factor-alpha (TNF-alpha) in the middle ear effusions (MEEs) of children with otitis media with effusion (OME) in relation to the chronicity of the disease and the presence of upper respiratory tract infection (URTI). STUDY DESIGN: In a retrospective study 140 MEEs were collected from 101 children between 2 and 12 years of age, and evaluated for the cytokine TNF-alpha and the lipopolysaccharide endotoxin. The amounts were quantified and correlated with the type of MEE, OME duration, and the presence of URTI. METHODS: Endotoxin levels were measured using a limulus amebocyte lysate assay and TNF-alpha levels were measured with an enzyme-linked immunosorbent assay (ELISA). Means of the different variables were compared using the one-way ANOVA least significance difference test with P<.05. RESULTS: In MEEs classified as mucopurulent (22.8%) both endotoxin and TNF-alpha levels (11.9+/-3 ng/mg total protein and 61.1+/-21 pg/mg total protein, respectively) were significantly higher compared with serous- (23.6%) or mucoid- (53.6%) type effusions. Fifty-five percent of the children who were classified as having chronic OME also had significantly higher amounts of endotoxin and TNF-alpha. The majority of the children (61%) had no URTI, although children with URTI (36%) did also have significantly higher levels of endotoxin and TNF-alpha in their middle ears. CONCLUSIONS: These results indicate that there is a strong correlation between the endotoxin and the TNF-alpha concentration in the middle ear and the type of MEE, the presence of URTI, and the chronicity of the disease.

Effect of endotoxin on cultured human middle ear epithelium.

The effect of endotoxin was investigated on air-exposed cultured human middle ear epithelium. Concentrations of 0, 1 and 100 ng/ml endotoxin were used. Complete differentiation of the cells was not reached at 12 days. After 21 days, endotoxin had induced an increased proliferation of the epithelial layer. Furthermore, an increase in the number of secretory cells and in the amount and length of microvilli was observed at this time. There were no significant morphological differences between the high and the low endotoxin concentrations, which supports our hypothesis that endotoxin induces an all-or-nothing reaction. These findings are in agreement with our previous results on serially submerged cultured rat middle ear epithelium. From these results we conclude that endotoxin is an important factor in the disturbance of the morphology of the middle ear epithelium, which may lead to chronic otitis media with effusion. In addition, our tissue culture method proved to be a good model for further studies on human middle ear mucosa.

The prognostic value of electrocochleography in severely hearing-impaired infants.

This paper presents a longitudinal evaluation of electrocochleographic assessment in severely hearing-impaired infants. Electrophysiological data were obtained by transtympanic electrocochleography to tone-burst stimuli at octave frequencies of 500 to 8000 Hz at the age of 0-6 years in a group of 126 subjects. The results are compared with auditory thresholds determined at school age in the same children by means of pure-tone audiometry. Cochlear microphonics could be recorded in virtually all ears, although the majority of subjects had hearing losses of 90 dB and more. Compound action potentials (CAPs) showed waveforms varying from normal to a wide range of abnormalities. Audiometric thresholds correlated generally well with the compound action potential (CAP) thresholds obtained in infancy. The error in the predicted audiometric thresholds is between 15 and 20 dB, as compared with 11 dB reported for more moderate hearing losses. It is shown that, in spite of the high stimulus levels used, substantial frequency-specific threshold information is retained. Occasional large discrepancies in thresholds were often associated with markedly abnormal response waveforms. Among the many cases in which no ABR could be elicited, 68 per cent produced detectable electrocochleographic responses in the 1000-4000 Hz range. It is concluded that electrocochleography is a valuable method for the assessment of residual hearing in infants suspected of having a severe hearing impairment.

Structural changes in the rat middle ear mucosa due to endotoxin and eustachian tube obstruction.

The middle ears of 48 rats were used to examine the effects of endotoxin injection, eustachian tube obstruction or a combination of eustachian tube obstruction and endotoxin injection. Animals were killed after 1, 2, 4, or 12 weeks and the middle ears processed for light and scanning electron microscopy. Compared to the normal middle ear mucosa, the epithelial layer was more pseudostratified, cuboidal or cylindrical after endotoxin injection or obstruction of the eustachian tube. In the early phase, numerous ciliated cells occurred in areas originally almost devoid of these cells. At 3 months, degeneration of ciliated cells was observed. The combination of eustachian tube obstruction and endotoxin injection also induced a more pseudostratified, cuboidal or cylindrical epithelium with an increased number of goblet cells. However, an early decrease occurred in the number of ciliated cells in the tympanic orifice of the eustachian tube. Furthermore, inflammatory cells, mainly PMNs, macrophages and lymphocytes, invaded the subepithelial layer after eustachian tube obstruction and endotoxin injection. These structural changes resulted in an impairment of the mucociliary transport system for clearance of the middle ear cavity. For this reason we believe that both endotoxin and eustachian tube obstruction or dysfunction play an important role in inducing persistent mucosal changes in the middle ear cavity, thereby prolonging otitis media with effusion.

[Physical diagnostic procedures: whispered speech and tuning fork test]. / Fysische diagnostiek--fluisterspraak en stemvorkproeven.

Hearing impairment occurs in 10% of the Dutch population and may lead to major communication problems and even social isolation. A good method to detect hearing loss in a general practice is the screening audiometer. The treating physician may further use the whispered speech test and tuning fork tests which together give a good impression of the severity and the nature of the hearing loss if any. The whispered speech test is best performed in the standardized form according to the guideline 'Slechthorendheid' [hardness of hearing] of the Dutch College of General Practitioners (NHG), in which certain combinations of letters are recommended. The tuning fork tests according to Rinne and Weber indicate a difference in perception and conduction deafness, and are decisive for any hearing asymmetry. Use of the whispered speech test and of the tuning fork tests is recommended for adults and children from the age of 7.

Results of cavity reconstruction with hydroxyapatite implants after 15 years.

OBJECTIVE: The results of the first cohort of 60 cavity reconstructions with hydroxyapatite with a minimum follow-up period of 15 years were studied. STUDY DESIGN: The study design was a retrospective study. PATIENTS: A total of 60 patients had a follow-up period of >15 years. In four patients, not all data were available. Therefore, 56 patients were included in the study. They had a combination of cavity problems and hearing loss. INTERVENTION: The ear canal was reconstructed with a canal wall prosthesis of porous hydroxyapatite. The ossicular chain was reconstructed with an incus or incus-stapes prosthesis of dense hydroxyapatite. RESULTS: After 15 years, 42 patients (75%) had an intact reconstructed ear canal. The main problem for failure was the recurrent purulent middle ear infection and not cholesteatoma. The histology of the retrieved canal wall showed a good remodeling in living bone tissue. After 15 years, 34 patients had a normal ear canal and an ossicular chain. Of these patients, 7.05% had an air-bone gap closure within 20 dB. CONCLUSIONS: Long-term results of cavity reconstruction with hydroxyapatite are possible. The main problem is recurrent mucosal disease of the new middle ear-mastoid cleft.

Risk factors for otitis media with effusion in children 0 to 2 years of age.

PURPOSE: To determine the possible risk factors associated with the occurrence of otitis media with effusion. PATIENTS AND METHODS: Two hundred eighty-nine children born between July 1987 and October 1988 were studied up to the age of 24 months. The enrollment of the children took place during their regular check-up visits at three different health-care centers. RESULTS: Having older sibling was the most important risk factor, for both the time elapsed until the first occurrence and for the probability of otitis media with effusion at each visit. Other significant risk factors for the probability at each visit were: having had acute otitis media before the visit or before the previous visit, age, a positive family history of otitis media, and upper respiratory tract infections (URTI). CONCLUSION: Having older siblings is the most important risk factor for otitis media with effusion in this age group.

Structural variations of the supratubal recess: the anterior epitympanic space.

HYPOTHESIS: We sought to classify the shape and structure of the anterior epitympanic space (AES) and produce measurements of its dimensions together with its relationships with the facial nerve and geniculate ganglion. BACKGROUND: The AES is limited by the middle cranial fossa superiorly, zygoma root anteriorly, cog posteriorly, chorda tympani laterally, facial nerve medially, and tensor tympanic semicanal inferiorly. METHODS: The AES was examined in 30 human temporal bones using two different methods. Twenty bones were cut vertically and a modified radical mastoidectomy was performed in the other 10 bones. RESULTS: The AES showed two types in the vertically cut bones according to its shape and structure. Type I, found in 17 (85%) of the bones, showed two cavities that were separated by a bony landmark and the tensor tympanic fold. The name "supratubal ridge" is suggested for this bony landmark. In type II, which was seen in three (15%) of the bones, there was only one cavity. In the mastoidectomy group, again two types of AES were found: eight (80%) were type I and two (20%) were found to be type II. If we combine these findings with the vertically cut bones, we find that 25 (83.3%) possess an AES type I, whereas five (16.7%) are type II. CONCLUSIONS: These variations in the structure of the AES and its close relationships with a number of vital structures such as the facial nerve, cochlea, and middle fossa dura must be taken into account during the surgical management of middle ear disease.

[Antibiotics in otitis media with effusion]. / Antibiotica bij otitis media met effusie.

Otitis media with effusion usually resolves spontaneously. If not, long-term hearing impairment has to be prevented. The available literature indicates that antibiotic treatment has at most a short-term effect. Therefore it is not indicated for the treatment of otitis media with effusion.

Response thresholds in electrocochleography and their relation to the pure tone audiogram.

OBJECTIVE: The relations between response thresholds obtained by 1) transtympanic (TT) and 2) extratympanic (ET) electrocochleography, and by 3) pure tone audiometry, were investigated in a population of patients with cochlear hearing loss of various types and degrees, with the prediction of audiometric from electrocochleographic thresholds as the primary focus. DESIGN: Analyses were made of the relation between TT response thresholds for tone bursts with octave frequencies from 500 to 8000 Hz and audiometric thresholds in 148 ears. Similar analyses of ET thresholds were given for a subset of 30 ears in which TT and ET physiological responses were simultaneously recorded. RESULTS: TT electrocochleographic thresholds are highly correlated with audiometric thresholds. Linear regression analysis shows that audiometric thresholds can be predicted from physiological thresholds with an error in the estimate of 11 dB. ET electrocochleography permits similar predictions but with a larger uncertainty of 16 dB. Both methods demonstrate a clear frequency specificity. As a remarkable secondary observation, it appears that electrocochleographic thresholds increase slightly less with increasing cochlear dysfunction than do pure tone thresholds. The hypothesis is elaborated that this is due to the different stimulus durations on which the two threshold measurements are based in interaction with the difference in temporal integration between normal and pathological ears. CONCLUSION: Electrocochleography is a powerful method for the objective and frequency-specific determination of cochlear response thresholds. TT recording is the preferred method, but ET recording is suitable with a larger uncertainty in the estimate. Electrocochleographic thresholds directly measure the cochlear sensitivity as such, whereas pure tone thresholds measure the combination of loss of cochlear sensitivity and of reduced temporal integration.

Input/output curves to tone bursts and clicks in extratympanic and transtympanic electrocochleography.

OBJECTIVE: The aim of this study is to explore the applicability of two specific methods in extratympanic (ET) electrocochleography that have rarely been used there, but are more commonly applied in transtympanic (TT) approaches. These two methods are the use of tone burst stimulation in addition to clicks, and the analysis of amplitude input/output curves as a measure of cochlear recruitment due to a pathological spread of excitation. DESIGN: Simultaneous extratympanic and transtympanic recordings were made in 30 patients with various types and degrees of cochlear hearing loss. ET recordings were also made in a group of normal subjects. Stimuli were tone bursts at octave frequencies from 500 to 8000 Hz and clicks, at intensity levels of about 90 dB down to response threshold in 10 dB steps. First, a general comparison is made of ET versus TT response properties, then the initial slopes of I/O curves in both sets of data are evaluated. RESULTS: ET responses are reduced in amplitude with respect to TT responses by a factor of 0.43 on average. Within each subject this factor is independent of stimulus type or level, but it has a substantial intersubject variation. ET and TT latencies are identical. From the normal data a criterion for abnormality of the slope of the I/O curve is derived in a similar way as available for TT data. Using this criterion ET I/O curves appear to be significantly steeper than normal in recruiting ears, albeit with a lesser sensitivity than for the associated TT data. CONCLUSIONS: Extratympanically recorded responses to tone burst stimuli provide basically the same information as transtympanic recordings. However, for a reliable interpretation of responses to low-intensity stimuli a larger amount of signal averaging is required. The analysis of I/O curves is a useful extension of current ET methods as a contribution to assessing a pathological spread of excitation in the cochlea.

Total artificial middle ear: preliminary report.

Reconstruction of a totally empty middle ear is difficult. This study reports results of 15 patients implanted with a total artificial middle ear developed on the principles of a total homologous middle ear and consisting of a canal wall prosthesis, a tympanic membrane/malleus prosthesis, and an incus/stapes prosthesis. Satisfactory results were noted in 12 of 15 patients at 1-year follow-up, with air-bone gap closure within 30 dB; within 20 dB in seven of these twelve. However, at 3-year follow-up examination the total artificial middle ear was removed in seven cases due to obliteration and infection of the middle ear. These failures related to the extensive middle ear disease initially noted in these seven patients. These long-term results indicate the necessity of careful patient selection for reconstruction.