Evolution of middle ear changes after permanent eustachian tube blockage

OBJECTIVE: To develop a valid animal model for otitis media with effusion (OME). DESIGN: Forty specific pathogen-free Wistar rats underwent a procedure based on the permanent obstruction of pharyngeal eustachian tube by means of electrocoagulation without any manipulation. SETTING: Ear Research Group, Department of Otorhinolaryngology, Puerta de Hierro Hospital, Universidad Autonoma de Madrid, Madrid, Spain. MAIN OUTCOME MEASURES: The assessment of OME by otoscopy and tympanometry. The rats were humanely killed at 15 and 90 days, and temporal bones were obtained and processed for histopathologic study. RESULTS: The histopathologic study of the temporal bones demonstrated the occurrence of chronic effusion and mucosal changes owing to mucoperiosteal enlargement. CONCLUSIONS: Comparison with other experimental models was made. Our animal model was consistent and reproducible and resembled human OME.     

Panel discussion: Pathogenesis of otitis media. Bacteriology and immunology

Three features of otitis media with effusion (OME) are important in understanding its pathogenesis: 1. it is most common among children, when the eustachian tube is poorly developed; 2. it is most common during the winter months, when the common cold is prevalent; and 3. bacteria are found in a large number of middle ear effusions from OME patients. Although middle ear effusions are conventionally thought to be sterile, numerous recent investigations favor a bacterial pathogenesis of OME. Four possibilities can be considered: 1. bacteria are modified by antibiotics or antibodies, causing a lingering inflammation; 2. early antibiotic treatment may interfere with the development of local immunity; 3. bacterial antigen trapped in the middle ear causes immune injury leading to OME; and 4. bacterial endotoxin and inflammatory mediators cause middle ear effusions.     

Mastoid size and otitis media with effusion: Question of correlation

Objectives/Hypothesis: To determine the incidence of otitis media (OME) with effusion on histologic examination in temporal bones with mastoid cavities reduced by the fenestration procedure for otosclerosis. Study Design: Temporal bone histologic study. Methods: Light-microscopic examination of serially sectioned temporal bones. Results: The incidence of otitis media with effusion in temporal bones with prior fenestration operation was not any more frequent than the control group of temporal bones with surgically unaltered mastoid cavity. Conclusions: There is no increased incidence of otitis media with effusion in temporal bones with prior fenestration operation.     

Experimental conditions for the development of persistent otitis media with effusion

Summary The purpose of this study was to investigate sufficient conditions for the development of long-lasting otitis media with effusion (OME) without any organic obstruction of the eustachian tube. Three experimental conditions were employed using 20 adult cats (27 ears). Only tubal ventilatory dysfunction with transection of the tensor veli palatini muscle and excision of the pterygoid hamulus resulted in a small incidence of OME (7.1%), which lasted for 5 weeks. Instillation of Escherichia coli endotoxin into the middle ears formed only a transient OME in 50% of the animals. Combination of these two procedures brought a high incidence of OME (85.7%), most of which lasted for more than 8 weeks. These studies showed that tubal ventilatory dysfunction alone was not a sufficient condition for the development of OME but was important for prolongation of the pathological state of OME. The production of inflammatory exudate was considered to be a trigger for the formation of OME.Offprint requests to: H. Takahashi     

Sensorineural hearing loss in experimental purulent otitis media due to Streptococcus pneumoniae

Sensorineural hearing loss (SNHL) has been described clinically following chronic otitis media with effusion, but to the best of our knowledge, no studies have demonstrated SNHL in an animal model of otitis media. Using the chinchilla model of pneumococcal otitis media, significant SNHL was demonstrated after purulent otitis media, especially at higher frequencies. Animals with otitis media received penicillin G procaine treatment for five days after otitis media with effusion (OME) was first documented; resolution of middle ear infection was confirmed by middle ear effusion culture in all animals. Both the inoculated and uninoculated ears were examined by tone burst-elicited compound action potential at threshold. The inoculated ear showed a marked hearing loss of 13 to 36 dB three to four days after OME was first documented; a hearing loss up to 24 dB persisted two to five weeks after inoculation. The change in the compound action potential was highly significant at all frequencies studied. Conductive losses were largely ruled out because there was no middle ear effusion at death and the tympanogram was normal. Purulent labyrinthitis was ruled out by histopathological study. These results indicate that purulent pneumococcal otitis media in the chinchilla model causes significant SNHL and suggest that the pathogenesis of SNHL associated with chronic OME in humans may be studied in this model.     

Findings at initial surgery for childhood otitis media with effusion and subsequent outcome

The outcome of initial surgical treatment in children with otitis media with effusion (OME) was analysed in a prospective study involving 225 new patients. The presence or absence of effusion in each ear and type of effusion present were recorded at surgery. The outcome measure studied was resolution or recurrence of middle ear effusions necessitating further surgical intervention. The outcome was significantly more favourable in children with unilateral effusions at surgery as opposed to bilateral effusions (P> 0.03) but was unrelated to the type of effusion (serous or mucoid). Patients with unilateral effusions at surgery appear to have a fluctuating form of OME in which effusions are present in either or both ears at different times.     

The role of Mucodyne® in reducing the need for surgery in patients with persistent otitis media with effusion

A recent meta‐analysis suggested a possible beneficial effect of carboxymethylcysteine (Mucodyne^®) in resolving otitis media with effusion (OME), but the methodology in several of the included trials was flawed. A double‐blind randomised controlled trial (RCT) involving 163 patients (78 randomised to Mucodyne^® and 85 to placebo) was therefore performed. Main outcome measure: operative intervention or not. Of the 28 patients with resolved OME, 17 were in the Mucodyne^® group and 11 in the placebo group. Although it appeared that patients treated with Mucodyne^® were 1.68 times more likely to undergo resolution of OME than patients receiving placebo, this did not reach statistical significance. [Risk ratio of 1.68 (95% C.I., 0.74–3.37)]. χ² test (df = 162) = 2.24 (P= 0.134). The absolute risk difference in the study was 8.5% (95% C.I., ‐3–20). We cannot exclude the possibility that Mucodyne^® is as beneficial as a 20% additional resolution of OME, or as harmful as a 3% decrease in the resolution of OME.     

Adherence of Haemophilus influenzae to nasal,nasopharyngeal and buccal epithelial cells from patients with otitis media

Summary Since mucosal colonization may be an important determinant in the pathogenesis of otitis media with effusion (OME), we studied the adherence of Haemophilus influenzae (HI) to human nasal, nasopharyngeal, and buccal mucosal cells obtained from patients with OME. Non-typeable HI adhered in significantly greater numbers than type b HI. HI bacteria adhered to both nasal and nasopharyngeal mucosal cells in significantly greater numbers than to buccal ones. Non-typeable HI adhered to the epithelial cells from children with chronic sinusitis in more significant numbers than did those from children without chronic sinusitis. These results indicate that non-typeable HI adhere more readily to epithelial cells and that the nasal and nasopharyngeal mucosa may be an important route for HI infection in OME. Offprint requests to: T. Harada     

Microbiology of chronic and recurrent otitis media with effusion in young infants

Chronic otitis media with effusion (OME) has been assumed to be sterile, since several reports in the literature have described unsuccessful attempts to culture bacteria from it. However, several recent studies have confirmed an earlier report that there is a significant frequency of bacteria in the middle ears of children with chronic and/or recurrent OME. Similar studies in young infants with chronic and/or recurrent OME have not been previously reported. In this study, cultures were obtained at the time of myringotomy and tympanostomy tube insertion from 50 infants aged 1–12 months who had chronic and/or recurrent OME. From the 80 ears of 40 infants without cleft palate, 32% had bacteria isolated from their middle ears; 22% had Streptococcus pneumoniae or Haemophilus influenzae. In 21 of these ears, no effusion was apparent at myringotomy, but in 28% bacteria were isolated from middle ear washings. From the 20 ears of 10 infants with an unrepaired cleft palate, 55% had bacteria present in their middle ear aspirates; 50% had S. pneumoniae or H. influenzae. Even though the significance of bacteria in chronic OME in children, and now in young infants, is unclear at present, a therapeutic trial with an antimicrobial agent prior to surgical intervention would appear to be reasonable until such therapy is tested in a randomized, clinical trial.     

Clinical approaches for understanding the expression levels of pattern recognition receptors in otitis media with effusion

Objectives

Bacterial infections in the normally sterile environment of the middle ear cavity usually trigger host immune response, whereby the innate immune system plays a dominant role as the host''s first line of defense. We evaluated the expression levels of Toll-like receptors (TLRs) -2, -4, -5, -9, and nucleotide-binding oligomerization domain-containing proteins (NODs) -1 and -2, all of which are related to bacterial infection in pediatric patients with otitis media with effusion (OME).

Methods

The study sample consisted of 46 pediatric patients with OME, all of whom had ventilation tubes inserted. The expression levels of TLR-2, -4, -5, -9, NOD-1 and -2 mRNA in middle ear effusion were assessed by polymerase chain reaction (PCR). Difference of pattern recognition receptors (PRRs) expression level by presence of bacteria, ventilation tube insertion rate, and effusion fluid character was assessed.

Results

All effusion fluid samples collected from patients with OME showed expression of TLR-2, -4, -5, -9, NOD-1, and -2 mRNA by PCR. However, we found no differences among expression levels of PRRs in relation to characteristics of exudates, presence of bacteria, or frequencies of ventilation tube insertion (P>0.05).

Conclusion

Our findings suggest that exudates of OME patients show PRR expressions that are related to the innate immune response regardless of the characteristics of effusion fluid, presence of bacteria in exudates, or frequency of ventilation tube insertion.     

中性粒细胞胞外诱捕网络在分泌性中耳炎中的作用及其研究进展

分泌性中耳炎(OME)是以传导性聋及鼓室积液为主要特征的中耳非化脓性疾病。冬春季多发,是儿童和成人听力下降的常见原因。部分患者的病程过长,最终导致黏连性中耳炎、胆脂瘤等病变,形成不可逆的听力损害。OME的发生发展主要与咽鼓管功能障碍、中耳局部感染和变态反应相关,但是,其病理机制目前尚不明确。中性粒细胞胞外诱捕网络(NETs)作为中性粒细胞捕获和杀灭病原体的一种新作用机制,参与循环、呼吸、肿瘤及自身免疫性疾病的发生和发展;并且作为新的治疗靶点,NETs的抑制剂对这些疾病的治疗已经取得了一定进展。前期研究在OME患者或动物模型的中耳积液中发现了NETs相关蛋白,提示NETs也参与OME的疾病进展。本文就NETs在OME中的作用及其研究进展作一综述。     

A prospective study of otitis media with effusion in adults and children

A prospective study of otitis media with effusion (OME) in both adults and children has been carried out. 75 new adult patients were seen during a 4-year period. Of these, 13 had associated diseases which could reasonably be considered to have been a cause of their effusion. Over a 2-year period, 192 new children with OME were seen. There was a significantly higher incidence of previous otalgia and/or aural discharge in the children as compared to the adults (P ≤ 0.001). The adults had significantly more serous effusions than the children (P ≤ 0.001), but both mucoid and serous effusions occurred in both groups. Similar rates of spontaneous resolution were observed in the 2 groups. Within the adult group, patients with a history of upper respiratory infection at the onset of hearing loss were significantly more likely to have spontaneous resolution of their effusion (P ≤ 0.02).     

A prospective study of otitis media with effusion in adults and children.

A prospective study of otitis media with effusion (OME) in both adults and children has been carried out. 75 new adult patients were seen during a 4-year period. Of these, 13 had associated diseases which could reasonably be considered to have been a cause of their effusion. Over a 2-year period, 192 new children with OME were seen. There was a significantly higher incidence of previous otalgia and/or aural discharge in the children as compared to the adults (P less than or equal to 0.001). The adults had significantly more serous effusions than the children (P less than or equal to 0.001), but both mucoid and serous effusions occurred in both groups. Similar rates of spontaneous resolution were observed in the 2 groups. Within the adult group, patients with a history of upper respiratory infection at the onset of hearing loss were significantly more likely to have spontaneous resolution of their effusion (P less than or equal to 0.02).     

Relationship between effusion bacteria and concentrations of immunoglobulin in serum and effusion fluid in otitis media with effusion patients

OBJECTIVE: Bacterial infection and immunity are important in the development of otitis media with effusion (OME) in children who have not developed Eustachian tube function. We evaluated the relationship between the presence of bacteria in effusion fluid and immunoglobulin (Ig) concentrations in effusion fluid and serum. METHODS: Middle ear effusion and blood samples were collected from 58 OME patients who had undergone ventilation tube insertion. Bacteria in effusion fluid were detected by standard bacterial culture and polymerase chain reaction (PCR). Serum and middle ear fluid Ig concentrations in OME patients and serum Ig concentrations in 64 control children were evaluated. RESULTS: Bacteria were detected in 24/58 (41.4%) effusion fluid samples by PCR and in 12/58 (20.6%) by standard culture. There was no correlation between effusion Ig concentration and the presence of bacteria or between serum and effusion Ig concentrations, but serum Ig concentration was related to the presence of effusion bacteria (p<0.05). Serum IgG, IgA and IgM in patients with OME were lower than in control patients (p<0.05). CONCLUSIONS: These results suggest that the presence of effusion bacteria in OME may be related to systemic immunity, but that the concentration of Ig in effusion fluid may not be affected by the presence of effusion bacteria.     

Clinical outcomes of otitis media with effusion following palatoplasty in patients with incomplete cleft palate

Background: Diagnosis and treatment strategies for CP with OME and the timing of ear tube insertion remain controversial.

Objectives: To analyze the clinical outcomes of otitis media with effusion in children with incomplete cleft palate after palatoplasty prospectively.

Methods: A total of 30 children (10 months–2 years old) with incomplete CP were enrolled in this study and received at least 6 months of follow-up evaluations after palatoplasty.

Results: The overall improvement rate of OME was as high as 26% in this group. Average air conduction hearing threshold was significantly better than that before surgery in the 8 patients with improved OME (p?<?.05). Among the 8 children with improved OME, 7 (87.5%) were found to have middle ear effusion that improved within 6 months after CP repair. There was no significant difference in the improvement rate between the severe degree II group and the mild group.

Conclusion: A 6-month follow-up period is recommended. The severity of incomplete CP is not fully related to the function of the eustachian tube.

Significance: The overall improvement rate was as high as 26%, and effusion in the tympanic cavity subsided in 7 out of 8 cases within 6 months after the CP repair.     

Expression of aquaporins mRNAs in patients with otitis media

Objective: This study analyzed the associations between measured levels of aquaporin (AQP) mRNAs and clinical manifestations in patients with various types of otitis media (OM).

Methods: AQP1, 2, 3, 4, 5, 6, 8, and 10 mRNA levels were assayed by real-time PCR from 57 patients with chronic otitis media (COM), 24 patients with cholesteatomatous otitis media (choleOM), and 82 patients with otitis media with effusion (OME). The relationships of these mRNA levels with the presence of bacteria, the type of hearing loss, and clinical manifestations of OM types were evaluated.

Results: All eight AQP mRNAs were expressed in inflammatory tissue, chole matrix, and effusion fluid obtained from all 163 patients with OM. The levels in OME of AQP2, 4, 6, and 10 mRNA; and the levels in choleOM of AQP1, 3, 4, and 10 mRNA were elevated significantly compared to the corresponding levels in COM (p?p?Conclusions: The levels of expression of AQP mRNA are associated with the pathophysiology of OM.     

Effects of low humidity on the rat middle ear

Secretory otitis media is common in the winter, and the possible risk factors are numerous. This study examines the effect of low humidity on the middle ear using a Sprague-Dawley rat model: 23 test rats housed for 5 days in a low-humidity environment (10% to 12% relative humidity) and 23 control rats housed at 50% to 55% relative humidity. Microscopic ear examinations were graded for otitis media with effusion (OME) before testing and on test days 3 and 5. The mucosa of the middle ears and eustachian tubes was examined histopathologically. Significantly more effusions were observed in the low-humidity group on test days 3 (P = .003) and 5 (P = .01), but no intergroup histopathologic differences were noted. We conclude that a low-humidity environment contributed to the development of OME in the test animals, and that low-humidity warrants further investigation as a contributing factor in childhood middle ear disease.     

The effect of the season on otitis media with effusion resolution rates in the New York Metropolitan area

OBJECTIVE: To study the relationship between season and resolution rates of otitis media with effusion (OME) in the New York Metropolitan area, in order to provide objective data useful to the practicing otolaryngologist in determining if seasonal factors should be considered in OME management decisions. METHODS: This was a prospective study of children referred to a tertiary medical center. Children with OME (confirmed by pneumatoscopy and tympanometry) were followed by an otologist at an academic medical center over a 3 years period. They returned approximately every 6 weeks until the end points of resolution of the effusions or ventilating tube placement. Each period between visits is termed an "interval." RESULTS: 127 patients with 231 effusions were followed for a total of 354 intervals. Effusions at intervals beginning in autumn were least likely to resolve by the next visit (24.29%) while intervals ending in the summer had the greatest rate of resolution (44.32%). Analyzed by month, the lowest rates of resolution were seen in intervals beginning in September, November, February, and March (16.67, 21.05, 20.51, and 19.15%, respectively). Intervals beginning in May had the greatest chance of resolution (51.72%). There was a positive correlation between resolution rates and average daily temperatures as reported by month. CONCLUSIONS: The season and month of the year are relevant factors in the clinical course of OME in the New York Metropolitan area. Based on the observed rates of resolution, one could reasonably consider taking a more conservative approach to OME management in May through August, and a more aggressive approach in the fall and winter months.     

Occurrence of Streptococcus pneumoniae and Haemophilus influenzae in otitis media with effusion

Eighty mucoid effusion samples obtained from 56 patients with otitis media with effusion (OME) were subjected to quantitative and qualitative bacteriological analysis using standard culturing methods, direct microscopy and immunofluorescent assay. 30% of the samples contained culture-positive pathogens (H. influenzae, S. pneumoniae, B. catarrhalis), with counts never exceeding 5 times 10⁵ per ml. In addition, 19% of the samples had dormant H. influenzae and S. pneumoniae, which did not grow on standard agar plates. Viable and dormant bacteria, as well as bacterial remnants, play a crucial role in the pathogenesis of OME and similarities between OME and reactive arthritis, i.e. Lyme arthritis, Reiter's syndrome and rheumatic fever, are evident.