Repeated Inflation Does Not Prevent Otitis Media With Effusion in a Monkey Model

Objective: Investigate the efficacy of repeated middle ear inflation with an inert gas (argon) for preventing the development of middle ear effusion in monkeys with functional eustachian tube obstruction. Study Design: Prospective controlled trial of daily middle ear inflation with five monkeys assigned to the inflation group and four to the control group. Methods: The right tensor veli palatini muscle of nine monkeys was paralyzed with botulinum toxin. Tympanometry was done before the procedure and then daily for 21 days. Presence and distribution of effusion were assessed before paralysis and on day 15 using magnetic resonance imaging (MRI). In five right ears inflation was done beginning at the first observation of negative middle ear pressure of ≤?200 mm H₂O and repeated on all days with pressures ≤?100 mm H₂O. Four right ears served as uninflated controls. Results: Right middle ear pressure decreased in all animals over the course of the study. Pressure returned to near-ambient levels immediately following the argon inflation but was decreased to control levels at the subsequent observation on the following day. MRI at day 15 documented effusion in all right ears with no quantifiable differences in amount or distribution between ears that were and were not inflated with argon. Conclusions: Repeated inflation with an inert gas does not prevent middle ear effusion in monkeys with functional eustachian tube obstruction.     

Behaviour of middle ear cleft mucosa during inflammation: Histo- morphometric study

Conclusion. This histo-morphometric study shows a significant reduction in the distance between the blood vessel's centre and the basal membrane of the middle ear cleft mucosa during inflammatory process. This could suggest that gaseous exchange is faster and more abundant in inflamed mucosa. The distance is significantly shorter in the postero-superior compartment of the middle ear cleft, possibly favouring a specific gas exchange function. Objectives. The aim was to try to understand the morphologic changes that occur when the middle ear cleft mucosa suffers from chronic inflammation. Materials and methods. Light microscopic computerized morphometry was used to measure the distance between the centre of the blood vessels and the basement membrane of the middle ear cleft mucosa. Results. In inflammation, the distance from blood vessel to mucosa is reduced in all five regions of the middle ear cleft. This distance is statistically the shortest in the postero-superior compartment of the middle ear cleft.     

氮气导入中耳腔治疗分泌性中耳炎疗效观察

目的 将氮气(N2)导入分泌性中耳炎患者的中耳腔，希望以此产生并维持长时间的中耳腔正压，达到治疗分泌性中耳炎的目的。方法 用咽鼓管导管吹张法将N2导入20耳分泌性中耳炎患者的中耳腔，用声导抗仪动态观察中耳腔压力的变化，并随访观察患者的症状、体征的变化，判断疗效；将结果与行空气吹张的另20耳分泌性中耳炎作对照组比较。结果 中耳腔在导入N2后能维持较长时间的正压和压力升高。但两组疗效的差别无统计学意义。结论 在治疗分泌性中耳炎时，N2导人中耳腔并未比一般的咽鼓管吹张(空气)显示出更好的疗效。     

Relationship between middle ear pressure,mucosal lesion,and mastoid pneumatization

Objectives: The inflammatory changes of pneumatic space mucosa are thought to affect the development of pneumatic space and the function of transmucosal gas exchange. So, it is assumed that the mucosal change is deeply involved in the onset and healing process of otitis media with effusion (OME). The objective of this study is to investigate whether the growth of the mastoid cells and the middle ear transmucosal gas exchange function in patients with OME are affected by the histopathologic changes in middle ear mucosa, and whether these two factors are changed by the treatment of OME. Materials and Methods: From 65 children with OME, middle ear mucosal specimens were collected during indwelling of a tympanic tube, and their histopathologic changes were compared with cell growth area measured on radiographic films and with the change in the middle ear total pressure (METP). Results: Suppression of the cell growth area was stronger and the METP stayed lower in cases with a higher degree of mucosal lesion. Significant expansion of pneumatic area was observed after 2 years of tube indwelling, and the peak METP showed a significant increase after 1.5 years. This increase in the METP was caused by diffusion/absorption of CO₂ and O₂ and indicated recovery of the transmucosal gas exchange function. Conclusions: The growth of the mastoid cells and the middle ear transmucosal gas exchange function are closely affected by the subepithelial histopathologic changes in middle ear mucosa, and these two factors recover by the treatment of OME.     

Influence of the Gas Exchange Function Through the Middle Ear Mucosa on the Development of Sniff-Induced Middle Ear Diseases

To investigate the influence of gas exchange function through the middle ear mucosa on the development of sniff-induced middle ear diseases, the authors examined the mastoid pneumatization among patients with sniffing habit using computed tomography, and also examined the change of negative middle ear pressure induced by sniffing using tympanogram. In 20 ears with cholesteatoma or adhesive otitis media, the areas of mastoid cavity measured at the level of the lateral semicircular canal were significantly smaller than those in 26 ears with otitis media with effusion (OME) or attic retraction and in eight normal ears with sniffing habit (P < .01 and P < .0001, respectively). In 26 ears with OME or attic retraction, the areas of mastoid cavity were significantly smaller than those in eight normal ears with sniffing habit (P < .0001). By contrast, in the four ears with sniff-induced middle ear disease, the recovery of negative middle ear pressure in 5 minutes without swallowing was less than 10 mm H₂O, whereas in all seven ears with normal eardrum, negative middle ear pressure recovered by more than 20 mm H₂O in 5 minutes. These findings suggested that impairment of gas exchange function through the middle ear mucosa, as well as eustachian tube dysfunction, might be closely related to the development of sniff-induced middle ear diseases.     

Behaviour of middle ear cleft mucosa during inflammation: histo- morphometric study

CONCLUSION: This histo-morphometric study shows a significant reduction in the distance between the blood vessel's centre and the basal membrane of the middle ear cleft mucosa during inflammatory process. This could suggest that gaseous exchange is faster and more abundant in inflamed mucosa. The distance is significantly shorter in the postero-superior compartment of the middle ear cleft, possibly favouring a specific gas exchange function. OBJECTIVES: The aim was to try to understand the morphologic changes that occur when the middle ear cleft mucosa suffers from chronic inflammation. MATERIALS AND METHODS: Light microscopic computerized morphometry was used to measure the distance between the centre of the blood vessels and the basement membrane of the middle ear cleft mucosa. RESULTS: In inflammation, the distance from blood vessel to mucosa is reduced in all five regions of the middle ear cleft. This distance is statistically the shortest in the postero-superior compartment of the middle ear cleft.     

Gas exchange function of the middle ear in patients with otitis media with effusion

Gas exchange function through the middle ear mucosa was assessed using nitrous oxide (N₂O) in patients with otitis media with effusion (OME), as well as in normal ears during elective surgery for unrelated disorders. In all normal ears except one (n = 43), an increase in pressure was observed after N₂O inhalation. In 42 of 84 ears with OME, a pressure increase was observed, but not in the remaining 42 ears (50%), indicating that the gas exchange function in these latter ears was impaired. In 21 of the 42 ears showing no middle ear pressure increase following N₂O inhalation, the middle ear pressure was again monitored after myringotomy and aspiration of the effusion A pressure increase was found in 16 ears, indicating that the impairment in gas exchange function in ears with OME may be reversible in most cases. Computed tomography of the mastoid was examined preoperatively in 66 ears, with the presence or absence of a middle ear pressure change well correlated in 57 ears with the presence or absence of mastoid aeration.     

Middle ear gas exchange via the mucosa: estimation by hyperventilation

CONCLUSION: It is thought that gas exchange via the mucosa occurred in relation to the partial pressure gradient, and it was impaired mainly by inflammatory changes in the mastoid mucosa. It was verified that gas exchange via the mucosa is less likely to be impaired than gas exchange via the eustachian tube. OBJECTIVES: To evaluate the capacity of middle ear gas exchange via the mucosa by examining the effect of hyperventilation on middle ear pressure. SUBJECTS AND METHODS: A total of 55 patients, 40 patients with a type A tympanogram and 15 with type C, were selected. Tympanometry was performed in one ear every 2 min while hyperventilation was forcibly continued for 44-6 min in the supine position. The middle ear pressure and the pressure of end-tidal carbon dioxide (PETCO2) was measured, and sonotubometry was performed. RESULTS: PETCO2 decreased gradually as hyperventilation continued in all cases. Although middle ear pressure decreased by hyperventilation in 49 of 55 patients, in 6 patients it hardly decreased despite the decrease in PETCO2. These six patients were treated for otitis media with effusion within 1 month before this examination.     

Carbon dioxide exchange via the mucosa in healthy middle ear.

BACKGROUND: Recent studies have shown that gas exchange via the middle ear mucosa, which is performed between the middle ear cleft and capillaries in the submucosal connective tissue, has an essential role in ventilation and pressure regulation in the middle ear cleft. We speculated that gas exchange via the mucosa is induced by the gas diffusion caused by the partial pressure gradient of gas between the middle ear cleft and submucosal capillaries. OBJECTIVE: To evaluate the capacity of the gas exchange via the mucosa in the healthy middle ear of humans by examining the effect of the respiratory mode on middle ear pressure. SUBJECTS AND METHODS: We selected 13 volunteers ranging in age from 25 to 44 years with healthy ear drums and type A tympanograms. Middle ear pressure was measured in 1 ear of each subject every 2 minutes using tympanometry while the respiratory mode was altered, with the subject in the supine position. RESULTS: The partial pressure of carbon dioxide in the venous blood (PvCO2) and middle ear pressure were decreased by hyperventilation and increased by hypoventilation. The partial pressure of oxygen in the venous blood showed little change. CONCLUSIONS: Carbon dioxide diffused into the blood from the middle ear cleft in accord with the partial pressure gradient when the PvCO2 was reduced by hyperventilation, resulting in a decrease of middle ear pressure, whereas CO2 diffused into the middle ear cleft when the PvCO2 was elevated by hypoventilation, resulting in an increase of middle ear pressure. These findings suggest that a bidirectional CO2 exchange via the middle ear mucosa functions in the normal human middle ear.     

Effects of inflammatory changes in the middle ear mucosa on middle ear total pressure

Conclusions. Inflammation of the middle ear mucosa leads to inhibition of transmucosal carbon dioxide (CO₂) diffusion. Furthermore, CO₂ diffusion is inhibited more severely in ears with a histologically higher grade of inflammation. Objectives. To investigate the effect of inflammatory changes in the middle ear mucosa on transmucosal gas exchange, and the relationship between the histologic inflammation grade of the middle ear mucosa and the middle ear total pressure (METP). Materials and methods. Twenty-six rabbits were used for this study. Changes in the METP and the oxygen partial pressure in the middle ear (PmO₂) were measured in the otitis media group and the untreated group, and were compared between the two groups. Inflammatory changes in the middle ear mucosa were classified into four grades histologically, and the relationship between the histologic inflammatory grade and the maximum METP was examined. Results. The maximum METP in the otitis media group was significantly decreased compared with the untreated group (p<0.05), but there was no difference between the two groups in the rate of decrease of the PmO₂. Furthermore, the maximum METP in grade III inflammation was significantly decreased compared with that in grade II inflammation (p<0.05).     

Clinical characteristics of so called eosinophilic otitis media.

OBJECTIVE: Although "eosinophilic otitis media" is not as uncommon a condition as was previously believed, its cause and pathogenesis are not yet fully understood. The purpose of this study was to describe the clinical characteristics in patients with "eosinophilic otitis media" to clarify its pathogenesis. METHODS: Seven adult patients with persistent and intractable otitis media with viscous middle ear effusion containing many eosinophils, who were also under treatment for bronchial asthma, were studied. The following examinations were conducted: nasopharyngeal endoscopy, pure-tone audiometry, eustachian tube function test, temporal bone CT scan, blood analysis, bacterial and fungal culture of middle ear effusion, histological study of the middle ear and nasal specimens, and measurement of eosinophilic cationic protein (ECP) in middle ear effusion. RESULTS: Some patients had persistent perforation with papillomatous granulation tissue arising from the mesotympanic mucosa, and all the patients had nasal polyposis. The pure-tone audiometry showed the mixed-type of hearing loss in all the patients, and the hearing level deteriorated progressively during the course in some patients. The eustachian tube function was not always poor but was patulous in some cases. The most severely diseased areas were in the eustachian tube and mesotympanum by temporal bone CT images. All the seven patients had the high levels of total serum IgE, but the RAST scores were negative in three patients and low grade in three patients. The accumulation of eosinophils was observed in middle ear effusion, middle ear mucosa and nasal polyps, and the eosinophils were highly activated with degranulation. High level of ECP was also recovered from middle ear effusion. CONCLUSIONS: Active eosinophilic inflammation occurs in the entire respiratory tract, including the middle ear in these patients. From our present investigation, we propose the criteria and clinical characteristics of "eosinophilic otitis media".     

Middle ear mucosa regeneration by grafting of artificial mucosa

Conclusion. Artificial middle ear mucosa (AMEM), a sheet of mucosal cells grown on collagen gel populated with fibroblasts, is useful as graft material that is able to promote mucosal regeneration after middle ear surgery. Objectives. Regeneration of the middle ear mucosa and pneumatization of the mastoid cavity is critical for good prognosis. We examined whether implantation of AMEM into damaged middle ear cavity would promote mucosal regeneration. Materials and methods. AMEM was prepared as described previously using epithelial cells and fibroblasts isolated from the rabbit middle ear. We implanted AMEM into rabbit middle ear from which mucosa had been surgically removed and evaluated its histological and functional recovery 8 weeks later. Three other groups were used for comparison: a normal control group, a mucosa-eliminated group, and a collagen-implanted group. Results. AMEM grew to be morphologically similar to the native middle ear mucosa. Electron microscope studies showed that implanted AMEM has basal lamina and cilia. AMEM implantation suppressed bone hyperplasia and granulation, leading to better mucosal regeneration. Mucosal gas exchange was also significantly improved after implantation.     

In vivo measurement of O2 and CO2 gas exchange across the human tympanic membrane

Conclusion. The hypothesis that the human tympanic membrane (TM) is permeable to CO₂ and O₂ at physiologic pressure gradients is supported but additional experiments need to be done to validate this methodology. Objective. Gas exchange between the middle ear and adjacent compartments determines the trajectory of middle ear pressure change. Little information is available regarding the permeability of the TM to physiological gases. This study aimed to determine in vivo if the human TM is permeable to O₂ and CO₂ at physiologic transTM pressure gradients. Subjects and methods. An ear canal (EC) probe (ECP) constructed from a custom-fitted acrylic body, a glass capillary tube enclosing an oil meniscus to maintain ambient ECP + EC pressure and a silica glass microtube linked to a mass spectrometer (MS) for measuring gas composition was hermetically sealed within one EC in each of 15 adults. ECP + EC volume was measured and gas samples were taken at 10 min intervals for 1 h. Epinephrine (1:100 000) was applied topically to the ipsilateral TM to decrease blood flow and the experiment was repeated. The ECP + EC pressures of O₂ (32 AMU) and CO₂ (44 AMU) were regressed on time and the slope divided by the predicted transTM partial-pressure gradients to yield estimates of transTM O₂ and CO₂ conductance. Results. Consistent with expectations for transTM gas exchange, ECP + EC O₂ decreased and CO₂ increased during the experiments. CO₂ increase was faster after application of epinephrine to the TM. The ratio of O₂/CO₂ conductances was not consistent with the gas exchange through a primarily water or lipid diffusion barrier.     

Effect of recombinant vascular endothelial growth factor on experimental otitis media with effusion

Conclusion This study demonstrates that rVEGF in the middle ear cavity contributes significantly to the development of OME by increasing the vascular permeability of the middle ear mucosa. Objective Vascular endothelial growth factor (VEGF) has been detected in otitis media with effusion (OME). It has a very strong effect on increasing vascular permeability, and is much more potent than platelet-activating factor, arachidonic acid metabolites or histamine. The purpose of this study was to investigate whether recombinant VEGF (rVEGF) can increase vascular permeability in the middle ear mucosa of rats. Material and methods rVEGF was injected transtympanically at doses of 0.01, 0.1 and 1.0 μg in the experimental groups; normal saline was injected in the control group. Twenty-four h after the injection of rVEGF, middle ear fluid was aspirated and the vascular permeability of the middle ear mucosa was measured by means of the Evans Blue vital dye technique. Results Extravasation of Evans Blue dye was found in all specimens injected with rVEGF, and was quantified using a spectrophotometer. Middle ear fluid developed in all ears injected with 0.1 or 1.0 μg of rVEGF and histopathology of the middle ear mucosa revealed severe inflammatory cellular infiltration, subepithelial edema and vascular dilatation. Rats injected with 1.0 μg of rVEGF showed a significant increase in middle ear vascular permeability in comparison with the control group (p<0.05).     

Effect of anesthetic gas on middle ear fluid

Tympanometry was performed before (preoperative) and after (intraoperative) the administration of inhalation anesthesia including nitrous oxide and halothane on 109 children undergoing myringotomy with pressure equalization tube insertion. A total of 213 preoperative tympanograms were compared with their intraoperative counterparts and the presence or absence of middle ear effusion at myringotomy. When preoperative tympanograms were consistent with pneumatized middle ears, intraoperative findings demonstrated a mean middle ear pressure increase of +147 daPa. When preoperative tympanometry suggested middle ear effusion, less than 1% demonstrated intraoperative tympanometric changes and/or findings at surgery that would support anesthesia clearing middle ear effusion. Preoperative tympanometric data were poor predictors of the presence or absence of effusion at myringotomy. The relationship between inhalation anesthetics (i.e., nitrous oxide and halothane) and middle ear fluids, and the reliability of tympanometry to predict middle ear effusion are discussed.     

Experimental otitis media induced by nonviable Moraxella catarrhalis in the guinea pig model

Moraxella catarrhalis is a normal resident of the human nasopharyngeal flora, but it is also isolated from middle ear fluid of acute otitis media and otitis media with effusion patients. To determine whether M. catarrhalis has direct pathogenicity in the middle ear, heat-killed M. catarrhalis was inoculated into the middle ear bullae of guinea pigs, and the inflammatory response was investigated. Middle ear mucosal histopathology observed in M. catarrhalis-inoculated ears included subepithelial edema, capillary dilatation, thickening of lamina propria mucosa, inflammatory cell and erythrocyte infiltration into the lamina propria mucosa. Inflammatory cell numbers, lysozyme and myeloperoxidase concentrations in the middle ear washing suspensions of M. catarrhalis-inoculated ears were significantly higher than control ears throughout the experiment. Therefore, nonviable M. catarrhalis induced middle ear inflammation and mucoperiosteal histopathology, which might be caused by direct injury of the nonviable bacteria (e.g. lipooligosaccharide or outer membrane proteins) and metabolic products of inflammatory cells.     

Ciliary beat frequency of nasal and middle ear mucosa in children with otitis media with effusion

Impaired mucociliary function of respiratory tract mucosa is associated with secretory otitis media in some well recognized syndromes. Ciliary activity per se may now be assessed directly by determination of ciliary beat frequency by a photoelectric technique.^1,2 49 children with otitis media with effusion undergoing surgical treatment were studied. Middle ear mucosa and nasal epithelial cells were obtained by biopsy and cytological brushings respectively at the time of surgery (myringotomy ± grommet insertion under general anaesthesia). From these samples mean nasal ciliary beat frequency was 11.0 Hz and mean middle ear ciliary beat frequency was 11.2 Hz. A positive correlation exists between mean ciliary beat frequency of nasal and middle ear samples from individual patients. A comparison of mean ciliary beat frequency between children who were effusion positive and effusion negative at the time of surgery revealed no statistically significant difference. In addition, no difference existed between those children with recurrent otitis media with effusion and newly presenting cases. No prima facie evidence exists of impaired ciliary function in this population of children with otitis media with effusion.     

An immunological study of otitis media with effusion. Antibodies directed against coagulase-negative staphylococci in the effusion fluid

Summary From 14 chronic middle ear effusions (MEEs), 17 strains of coagulase-negative staphylococci (CS) were isolated. We then used an ELISA method to determine the antibody titers against these microorganisms in the corresponding effusion fluids and the blood sera of the patients and compared them to the antibody titers against a group of standard CS. In most cases, no specific immune response could be detected against the infecting CS in either the effusion fluids or in the sera. Our results can be explained by the inability of most CS strains to provoke a specific immune response in chronically inflamed middle ears due to their inhibition by non-specific antibodies, which reach the middle ear cavity by plasma leakage. The non-specific antibody titer against Staphylococcus hominis, however, seems to be much lower than against the other CS species. We found a high specific antibody titer against the infecting CS in the effusion fluid of a single case, but not in the serum. This finding supports the hypothesis that the middle ear mucosa has the ability to produce autonomous, local antibodies which are independent of a systemic immune response.     

Measurement of middle ear pressure changes during balloon eustachian tuboplasty: a pilot study

Conclusion: The middle ear pressure changes detected during BET can be directly attributed to the balloon inflation and may represent a second, immediate, mechanism of action of BET. BET seems to be safe with respect to the risk of a barotrauma. Further human studies are now necessary to confirm the results and gain more insight into the mechanism of action of BET.

Objective: Since the introduction of Balloon Eustachian Tuboplasty (BET) as a treatment of chronic Eustachian tube dysfunction, the precise mechanism of action is unknown. Long-term effects of BET may be related to observed microfractures of the Eustachian tube cartilage. However, clinical observations indicate a second, immediate mode of action. Therefore, this study investigated and characterized middle ear pressure changes occurring directly during BET procedure.

Methods: Using a micro-optical pressure sensor, pressure changes during BET were monitored transtympanically in a cadaveric animal study using heathland sheep.

Results: Middle ear pressure amplitudes during BET are dependent on the speed of balloon inflation as well as the maximum inflation pressure. A 10-bar inflation pressure yielded a mean middle ear pressure of 5.34?mmHg (71.0 daPA). Negative pressure amplitudes occurring on withdrawal of the balloon catheter are influenced by the speed of withdrawal. No pressure amplitudes capable of causing barotrauma to membranous ear structures could be detected.