Bacterial biofilm in adenoids of children with chronic otitis media. Part I: a case control study of prevalence of biofilms in adenoids,risk factors and middle ear biofilms

Background: Biofilms are communities of bacteria embedded in a self-produced glycocalyx matrix. Adenoids have been shown to harbor bacterial biofilms.

Aim/objectives: To compare the prevalence of biofilms in adenoid of children with chronic otitis media (COM) (group1) versus a control group without any COM (group 2) having adenoids removed because of hypertrophy.

Material and methods: One hundred and three children were prospectively enrolled in this case-control study, group 1 (n?=?52) and group 2 (n?=?51). The main outcome measurement was the prevalence of biofilm in adenoidectomy specimens analyzed using confocal laser scanning microscopy. Children in group 1 who had middle ear (ME) effusion and requiring the insertion of a tympanostomy tube underwent biopsy of the ME mucosa and effusion sampling.

Results: Biofilms were found in adenoids’ specimens of both groups and in the ME biopsy and effusion. The biofilm prevalence in adenoids was 63.5% (33/52) in group 1 and 47.1% (24/51) in group 2. Day nursery and previous antibiotics intake were significantly more frequent in group 1 than in group 2.

Conclusions and significance: This case-control study demonstrates that adenoid tissue in children with COM contains more mucosal biofilms than adenoid tissue removed for hypertrophy. Biofilm was seen in ME biopsies and effusion.     

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.     

Effect of 23 valent pneumococcal polysaccharide and Haemophilus influenza conjugated vaccines on the clinical course of otitis media with effusion

Objective To determine if there is any clinical effect of 23‐valent pneumococcal and Haemophilus influenza type B conjugate vaccine on prognosis of otitis media with effusion. Method All children who have middle ear effusion despite long‐standing antibiotherapy with a beta lactamase stable agent were offered for tympanostomy tube insertion between February 1999 and December 2001. Patients who accepted the surgical intervention were operated under general anesthesia and a Shepard grommet‐type tympanostomy tube was inserted. Those who refused the surgical intervention were vaccinated with 23‐valent pneumococcal and Haemophilus influenza type B conjugate vaccine. State of the middle ear effusion was evaluated at the end of the 12th month in the vaccine group and 1 month after the myringotomy site was healed in the tympanostomy tube insertion group. Results Twenty‐six children in the vaccine group and 37 children in the tympanostomy tube insertion group proved the inclusion criteria at the end of study. Complete or partial resolution of middle ear effusion was observed in 73.1% of 26 children in the vaccine group and 59.5% of children in the tympanostomy tube insertion group. There was no significant difference between the two groups. Conclusion Vaccination against Streptococcus pneumonia and Haemophilus influenza type b seems to aid resolution of middle ear effusion in children with otitis media with effusion.     

Effect of irradiation on middle ear effusion due to nasopharyngeal carcinoma

The management of middle ear effusion by myringotomy and insertion of ventilation tubes in 75 adult patients was evaluated. In Group 1 the middle ear effusion was not related to nasopharyngeal carcinoma. The patients with nasopharyngeal carcinoma were subdivided into pre and post-radiotherapy groups (Group 2 and Group 3) according to the time of insertion of the ventilation tubes. Myringotomy and insertion of ventilation tubes achieved significant hearing gain in all three groups. The pre and post-radiotherapy groups had a higher post-operative infection rate than Group 1 (P > 0.01). The duration of a persistent tympanic membrane defect in the post-radiotherapy group was significantly longer than Group 1 (P = 0.03). The post-radiotherapy group had more perforations than Group 1 (P= 0.02). A total of 28% of ears in the post-radiotherapy group were discharging at the last visit. In view of the higher complication rate in the post-radiotherapy group, the role of myringotomy and insertion of ventilation tube is reassessed.     

Mechanisms of Tympanic Membrane and Incus Mobility Loss in Acute Otitis Media Model of Guinea Pig

Acute otitis media (AOM) is a rapid infection of middle ear due to bacterial or viral invasion. The infection commonly leads to negative pressure and purulent effusion in the middle ear. To identify how these changes affect tympanic membrane (TM) mobility or sound transmission through the middle ear, we hypothesize that pressure, effusion, and structural changes of the middle ear are the main mechanisms of conductive hearing loss in AOM. To test the hypothesis, a guinea pig AOM model was created by injection of Streptococcus pneumoniae. Three days post inoculation, vibration of the TM at umbo in response to input sound in the ear canal was measured at three experimental stages: intact, pressure-released, and effusion-drained AOM ears. The vibration of the incus tip was also measured after the effusion was removed. Results demonstrate that displacement of the TM increased mainly at low frequencies when pressure was released. As the effusion was removed, the TM mobility increased further but did not reach the level of the normal ear at low frequencies. This was caused by middle ear structural changes or adhesions on ossicles in AOM. The structural changes also affected movement of the incus at low and high frequencies. The results provide new evidence for understanding the mechanism of conductive hearing loss in AOM.     

Clinical and audiological findings in children with acute otitis media

Conclusion: It is recommended to perform follow-up tympanometry and if necessary tonal audiometry in children who have normal plain otoscopy findings after recovering from acute otitis media (AOM). Children with Type B tympanogram, 3 months following the onset of AOM, are very likely to have a conductive hearing loss. Type B tympanogram is a much better indicator of effusion in the middle ear compared to plain otoscopy. Objective: This study was undertaken to investigate the frequency and duration of middle ear effusion in children following an episode of acute otitis media, to track changes in tonal audiometry and tympanometry findings in the post-AOM period, and recognize the optimal timing for performing both tests. Methods: In this study, 125 children aged 5–7 years with bilateral AOM were randomly selected and separately followed up for 3 months. The children underwent six ear, nose, and throat (ENT 1–6) examinations, six tympanometries (TM 1–6), and three tonal audiometries (TA 1–3). Evaluation of nasopharynx was done at the ENT 1 examination. Children who received ventilation tubes were followed for 21 month altogether. Results: At the first otoscopy, pathological findings were recorded in 250 ears/125 children (100.0%). The number of pathological otoscopy findings decreased at each subsequent examination. At ENT 6 all children had normal otoscopy findings. Type B tympanogram was detected in 49/250 (19.6%) ears at TM 6, performed 3 months following the onset of the disease. At the TA 1 conductive hearing impairment was recorded in 158/250 (63.2%) ears, at TA 2 in 66/250 (26.4%), and at TA 3 in 39/250 (15.6%). Most of them were associated with Type B tympanogram.     

Clinical effects of clarithromycin on persistent inflammation following Haemophilus influenzae-positive acute otitis media

Conclusion: Additional treatment with clarithromycin (CAM) reduced persistent middle ear inflammation after acute otitis media (AOM) caused by Haemophilus influenzae in children. CAM is a treatment option for persistent inflammation following AOM and to prevent continuing otitis media with effusion. Objective: We conducted a clinical study to evaluate a new method of treatment for persistent inflammation after AOM in children. Methods: H. influenzae-infected children with AOM were treated acutely with antimicrobial agents, after which those still demonstrating effusion of the middle ear cavity received additional treatment with carbocysteine (S-CMC) alone or S-CMC combined with clarithromycin (CAM) for 1 week. The two regimens were compared in terms of clinical effects. Results: After the initial acute treatment, many patients still showed abnormal otoscopic findings. At the completion of additional treatment, there were no significant differences between the two treatment groups. However, 1 week after completion of additional treatment, the prevalence of a diminished light reflex was significantly lower in the CAM + S-CMC group than in the S-CMC group (p = 0.017). The prevalence of redness of the tympanic membrane also tended to be lower in the combined treatment group than in those receiving a single drug (p = 0.097).     

Conductive Hearing Loss Induced by Experimental Middle-Ear Effusion in a Chinchilla Model Reveals Impaired Tympanic Membrane-Coupled Ossicular Chain Movement

Otitis media with effusion (OME) occurs when fluid collects in the middle-ear space behind the tympanic membrane (TM). As a result of this effusion, sounds can become attenuated by as much as 30–40 dB, causing a conductive hearing loss (CHL). However, the exact mechanical cause of the hearing loss remains unclear. Possible causes can include altered compliance of the TM, inefficient movement of the ossicular chain, decreased compliance of the oval window-stapes footplate complex, or altered input to the oval and round window due to conduction of sound energy through middle-ear fluid. Here, we studied the contribution of TM motion and umbo velocity to a CHL caused by middle-ear effusion. Using the chinchilla as an animal model, umbo velocity (V _U) and cochlear microphonic (CM) responses were measured simultaneously using sinusoidal tone pip stimuli (125 Hz–12 kHz) before and after filling the middle ear with different volumes (0.5–2.0 mL) of silicone oil (viscosity, 3.5 Poise). Concurrent increases in CM thresholds and decreases in umbo velocity were noted after the middle ear was filled with 1.0 mL or more of fluid. Across animals, completely filling the middle ear with fluid caused 20–40-dB increases in CM thresholds and 15–35-dB attenuations in umbo velocity. Clinic-standard 226-Hz tympanometry was insensitive to fluid-associated changes in CM thresholds until virtually the entire middle-ear cavity had been filled (approximately >1.5 mL). The changes in umbo velocity, CM thresholds, and tympanometry due to experimentally induced OME suggest CHL arises primarily as a result of impaired TM mobility and TM-coupled umbo motion plus additional mechanisms within the middle ear.     

Neutrophil elastase-α1-antitrypsin in middle ear fluid in chronic otitis media with effusion

Neutrophil elastase-αl-antitrypsin was quantified in samples taken from middle ear effusions collected at operation from 17 children attending for elective myringotomy and grommet insertion. At the time of surgery the effusion was classified as serous or mucoid. Children with a recent history of infection or antimicrobial therapy were excluded. The quantification of immunoreactive neutrophil elastase was by means of enzyme-linked immunosorbant assay (ELISA). The mean value of neutrophil elastase-αl-antitrypsin was 50.6±38.3 (sd) μg/ml in mucoid effusions, which was significantly higher (P <0.05) than that in serous effusions (5.3±4.8 μg/m1). These results indicate that a mucoid effusion may reflect a more severe inflammatory response and that persistence of neutrophil activity in the middle ear mucosa may contribute to the persistence of at least one group of middle ear effusions.     

Ultrasound characterization of middle ear effusion

Purpose

To further enhance and assess the ability to characterize middle ear effusion (MEE) using non-invasive ultrasound technology.

Materials and Methods

This is a prospective unblinded comparison study. Fifty-six children between the ages of 6 months and 17 years scheduled to undergo bilateral myringotomy with pressure equalization tube placement were enrolled. With the child anesthetized, the probe was placed into the external ear canal after sterile water was inserted. Ultrasound recordings of middle ear contents were analyzed by computer algorithm. Middle ear fluid was collected during myringotomy and analyzed for bacterial culture and viscosity.

Results

Ultrasound waveforms yielded a computer algorithm interpretation of middle ear contents in 66% of ears tested. When a result was obtained, the sensitivity and specificity for successfully characterizing middle ear fluid content as either void of fluid, thick fluid (mucoid), or thin fluid (serous or purulent) were at least 94%. Mucoid effusions had higher measured viscosity values (P = .002). Viscosity measures were compared to culture result, and those with low viscosity (thin consistency) had a higher likelihood of having a positive culture (P = .048).

Conclusion

The device sensitivity and specificity for fluid detection were 94% or greater among interpretable waveforms (66% of those tested). Although this technology provides important information of the middle ear effusion presence and characteristic, further technological improvements are needed.     

Squamous cell metaplasia of the nasopharyngeal epithelium and its association with adult-onset otitis media with effusion

Conclusion

The common association between adult-onset otitis media with effusion (AO-OME) and squamous cell metaplasia (SCM) of the epithelium of Rosenmüller's fossa, which is near the Eustachian tube orifice, implies the predictive role of metaplasia, which probably compromises the drainage function of the middle ear.

Objective

To determine the effects of nasopharyngeal epithelial changes (SCM) on AO-OME. AO-OME is a multifactorial and insidious disease that may necessitate detailed investigation, i.e. biopsy of the nasopharynx, because of possible underlying nasopharyngeal malignancy.

Material and methods

Fifty-two patients with AO-OME (study group) and 29 with a unilateral neck mass in the posterior triangle without AO-OME (control group) were enrolled. Nasopharyngeal biopsies taken from all subjects were evaluated with regard to surface epithelial changes of the nasopharynx.

Results

Nasopharyngeal biopsies revealed SCM in 34/52 patients (65%) in the study group and 9/29 (31%) in the control group (p<0.05). During the follow-up period, recurrence of effusion occurred in 56% of the group with SCM and 22% of the group without it.     

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.     

Up-regulation of macrophage migration inhibitory factor induced by endotoxin in experimental otitis media with effusion in mice

Conclusion. Injection of endotoxin into the middle ear causes production of macrophage migration inhibitory factor (MIF) in an experimental mouse model of otitis media with effusion (OME). Down-regulation of MIF may become a new approach for the management of OME. Objective. To determine the role of MIF in OME. Materials and methods. Mice were divided into two groups and their middle ears were injected with either endotoxin or phosphate-buffered saline (PBS). Mice were sacrificed at 6 h, 12 h, or 1, 3, 7, or 14 days after injection and concentrations of MIF, interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in middle ear effusions were measured by enzyme-linked immunosorbent assay. Results. Concentrations of MIF in the endotoxin group at 1 day and 3 days were significantly higher than in the PBS control group. Concentrations of IL-1β in the endotoxin group at 6 h, 12 h, 1 day, and 3 days were significantly higher than in controls. Concentrations of TNF-α in the endotoxin group at 1 day and 3 days were significantly higher than in controls. Concentration of MIF in the endotoxin group was positively correlated with that of IL-1β and TNF-α.     

A Model to Explain the Rapid Pressure Decrease After Air–Inflation of Diseased Middle Ears

Objectives: Air-inflation in humans and monkeys with significant negative middle ear pressure or with middle ear inflammation was shown to cause greater than ambient middle ear pressure initially, followed by a rapid rate of pressure decrease to approach the preinflation value. Study Design: A mathematical model of middle ear pressure regulation is presented and used to simulate air-inflation of the normal and diseased middle ear. Materials and Methods: The model represents the total volume of the middle ear as consisting of three subcompartments representing the airspace, effusion, and mucosa/blood. Gas exchange among those compartments was assumed to be diffusion limited, and the gas exchange between the mucosa/blood compartment and systemic blood was assumed to be perfusion limited. Disease was modeled as an increase in mucosal blood flow or, alternatively, as an increase in the volumes of the effusion and mucosa/blood compartments. Results: The predictions of the model agree better with the experimental data when the increased rate of pressure change after middle ear inflation in diseased ears is driven by an increased volume of the effusion compartment as opposed to an increased perfusion rate. The responsible mechanism is a rapid redistribution among subcompartments of the gas volume introduced into the air compartment. Conclusions: These results suggest that middle ear inflation with inert gas can be used to diagnose the presence and relative amount of middle ear effusion, and that current protocols for treating otitis media with effusion using inflation need to be modified to optimize their intended effect.     

Tympanometric measurements in conscious sheep - a diagnostic tool for pre-clinical middle ear implant studies

Objective: To investigate and establish the use of tympanometry in conscious sheep to provide a means of objective assessment of tympanic membrane integrity, middle ear ventilation and functioning of the Eustachian tube (ET). Design: After conditioning the sheep for four weeks, tympanometric measurements at 226?Hz were carried out weekly for 13 weeks. Before measurements, the external ear canal had been cleaned. Resultant curves were classified according to human reference values. Study Sample: Tests were performed on 12 female blackface sheep. Results: After cleaning of the external ear canal under otoscopic control, tympanic membranes were intact with no evidence of acute or chronic middle ear inflammation, middle ear effusion or retraction. Cleaning ensured valid, objective and reproducible measurements. As the majority of normal tympanograms were notched without the appearance of any malformation, an additional tympanogram type (A_N) was introduced. The notched appearance can most likely be explained by the anatomy of the middle ear of the sheep and the test frequency that was used. Conclusion: The current study demonstrated how tympanometry can be used to evaluate treatment modalities for middle ear and ET function in conscious sheep. This provided a large animal model for further human research in otology.     

Distortion product otoacoustic emission together with tympanometry for assessing otitis media with effusion in children

Objective: To investigate the diagnostic value of distortion product otoacoustic emission (DPOAE) together with tympanometry in assessing otitis media with effusion in children.

Methods: Three hundred and thirty-nine patients, who were diagnosed with obstructive sleep apnea–hypopnea syndrome (OSAHS) and prepared to undergo adenotonsillectomy and had a unilateral or bilateral type ‘B’ or ‘C’ tympanogram were enrolled in this study. Patients were divided into the following four groups: Group 1, type ‘B’ tympanogram with positive DPOAE; Group 2, type ‘B’ tympanogram with negative DPOAE; Group 3, type ‘C’ tympanogram with positive DPOAE and Group 4, type ‘C’ tympanogram with negative DPOAE.

Results: Tympanometry showed a type ‘B’ pattern in 467 ears and type ‘C’ pattern in 163 ears. Among 163 ears with type ‘C’ tympanogram, negative DPOAE results were seen in 96 ears. Group 4 (56/96) had a significant high rate of middle ear effusion than Group 3 (14/67) (p?Conclusions: DPOAE could be a great help in screening for middle ear effusion in patients with a type ‘C’ tympanogram.     

Anterosuperior anchoring myringoplasty using cyanoacrylate glue can prevent packing gelfoam in the middle ear cavity

ObjectivesAlthough a number of methods have been attempted to improve securing the graft, packing gelfoam in the middle ear cavity cannot be avoided, which could obstruct the tympanic ostium of the Eustachian tube and affect inner ear function. Myringoplasty using tissue adhesive has gained traction because tissue adhesives can effectively stabilise the graft and act as scaffolding to improve the graft uptake. The aim of this prospective study was to explore myringoplasty using cyanoacrylate glue with no packing in the middle ear cavity for the repair of subtotal tympanic membrane (TM) perforations.MethodsBetween March 2014 and November 2015, 71 patients with subtotal TM perforations were randomly and prospectively divided into a glue group and a control group. Two securing techniques were performed using only cyanoacrylate glue or using only filling gelfoam in the middle ear cavity, respectively, during an anterosuperior anchoring myringoplasty operated by a single surgeon.ResultsAt a 6-month follow-up, the graft uptake rate was 87% in the glue group and 89% in the control group. A significant hearing improvement was found in both groups postoperatively when compared to the preoperative values (P < 0.05 for both). There was no significant difference in the graft uptake rate and hearing improvement between the 2 groups (P > 0.05). Similar complications were found in each group.ConclusionCyanoacrylate glue is a helpful material for graft stabilisation and can substitute for filling gelfoam in the middle ear cavity during anterosuperior anchoring myringoplasty for subtotal TM perforation.     

General Anesthesia With and Without Nitrous Oxide (N2O) and the Weight of Middle Ear Effusion in Children Undergoing Adenoidectomy and Tympanostomy

This study was designed to explore the effect of nitrous oxide (N₂O) on the amount of middle ear effusion. Seventy-six children referred for adenoidectomy or tympanostomy tube placement were divided into two groups in the basis of the method of anesthesia. One group of 39 children was ventilated with a mixture of 30% oxygen and 70% nitrous oxide, while the other group of 37 patients was ventilated with a mixture of oxygen and air. The amounts of middle ear effusion obtained in myringotomy were weighed and compared between these groups. Preoperative and perioperative tympanograms were performed. Ventilation with nitrous oxide caused a distinct rise in middle ear pressure. The amount of the middle ear effusion, however, remained the same in the two groups. It is concluded that the operating surgeon can rely on the myringotomy finding even when nitrous oxide anesthesia is used.     

Chronic otitis media with effusion and Helicobacter pylori

OBJECTIVE: The aim of this study is to investigate the presence of Helicobacter pylori (HP) in the middle ear effusion by Campylobacter-like organism (CLO) test and whether it has a role in the ethiopathogenesis of chronic otitis media with effusion (OME). STUDY DESIGN: A prospective randomized and controlled study. METHODS: This study was performed with 45 patients with the diagnosis of chronic OME and adenoid hypertrophy, between the ages 3 and 13 (median 6). Thirty patients constituted the study group (18 male (60%) and 12 (40%) female). Adenoidectomy with myringotomy with ventilation tube insertion were performed to this group. Middle ear effusion and adenoid tissue pieces were collected and H. pylori presence was investigated by "CLO" testing. Fifteen patients of the matching age group (9 male (66.7%) and 6 (33.3%) female) constituted the control group to whom adenoidectomy with myringotomy were performed but no middle ear effusion could be determined (empty myringotomy patients). The wash out liquid of middle ear and pieces of adenoid tissue samples were also collected from the control group. By using CLO testing, the presence of H. pylori was investigated in the adenoid tissues and middle ear of the empty myringotomy patients. RESULTS: In 20 (66.6%) patients of the study group, CLO testing was positive in the middle ear effusions. None of the patients demonstrated positive CLO test in the wash out liquid of middle ear. There was significant difference of positive CLO testing in the middle ear effusions of two groups (p<0.001). CONCLUSIONS: These findings showed us that presence of HP in the middle ear effusion using CLO testing and this may be responsible for the ethiopathogenesis of chronic OME.     

MRI findings of the middle ear in infants

Conclusions. While infants under the age of 1 year exhibited a high rate of abnormal intensities in the middle ear and mastoid cavities, older infants showed no abnormal intensities in these regions. From the signal intensity on T1- and T2-weighted MRI, the abnormal intensities in the middle ear cavity were considered to represent liquid effusion. Taken together with the findings of temporal bone CT, the abnormal intensities in the mastoid cavity were considered to represent bone marrow. Objective. Histopathological studies of the temporal bone and tympanometry investigations have reported the presence of mesenchyme and liquid effusion in the middle ear cavity of infants. However, very few CT or MRI middle ear cavity findings of newborns and infants have been published, and none have included the mastoid cavity. We therefore performed an MRI study of the middle ear and mastoid cavities of infants under 2 years old (83 cases, 88 imaging series). Subjects and methods. MRI (1.5 T) was originally performed on suspicion of brain disorders in infants aged under 2 years. All MRI slices were studied and classified on the basis of the distribution of abnormal intensities in the middle ear and mastoid cavities. Results. All the abnormal imaging appeared in infants under 1 year old, in particular, 74.24% (n=49) of abnormal imaging appeared in the first 20 weeks after birth.