Chronic otitis media with effusion (COME) refers to an inflammatory condition affecting the middle ear in which a nonsuppurative effusion is present behind a non-inflamed tympanic membrane for at least 3 months (1). The exact prevalence is unknown, but Browning and Gatehouse (2) estimated that it is 2.6% in adults.
The main etiopathogenetic factor of COME is Eustachian tube (ET) dysfunction due to either anatomical obstruction or a functional disorder (3,4). If no ET obstruction is present in the nasopharynx (e.g., adenoid hypertrophy, inflammation, carcinoma), tympanostomy has been used as the main therapeutic option. However, this traditional treatment has limited success mainly because it does not address the cause of the disease.
Transnasal balloon dilatation of the cartilaginous part of the ET, balloon Eustachian tuboplasty (BET), appears to be a promising therapeutic option for ET dysfunction and is becoming increasingly popular. Current studies have demonstrated the success of therapy in 70 to 90% of cases depending on the evaluated parameter and length of follow-up (7–10). However, the results are difficult to compare due to a lack of standardized evaluation protocols. Most studies have been conducted in non-homogeneous groups of patients. Patients with COME have been evaluated in the same group as patients with OME, patients with tympanic membrane adhesion, patients with an aerated physiological middle ear with symptoms of ET dysfunction only, or with patients after or during middle ear surgery (5–9).
Satisfactory data on the effect of BET in patients with COME are still missing. Liang et al. (10) was one of the very few to investigate this issue. However, only tympanogram and endoscopic findings were evaluated in their study; symptoms and hearing were not considered. Another unresolved issue is whether BET should be combined with tympanocentesis or tympanostomy. In most studies, the treatment is combined empirically (7–10), though satisfactory data allowing a clear conclusion are lacking.
The primary aim of this prospective randomized clinical trial was to determine if there is a beneficial outcome of BET combined with concurrent tympanocentesis compared with BET only in patients with COME. The secondary outcome was to provide additional comparable data on the effect of BET in patients with COME.
This study was approved by the Ethics Committee and performed in accordance with the Declaration of Helsinki and applicable regulatory requirements using good clinical practice. The study was registered at ClinicalTrials.gov under the identifier NCT03556215. Written informed consent was obtained from the patients before initiating any procedure. All authors reviewed and approved the final manuscript.
Design and Setting
This randomized clinical trial was performed between April 2016 and September 2018 in a tertiary referral hospital.
Adult patients suffering from unilateral or bilateral recurrent COME lasting more than 6 months after tympanostomy tube extrusion were included in the study. Diagnosis of COME was made if there was collection of non-purulent fluid in the middle ear with an intact tympanic membrane more than 3 months and tympanometry matched this finding. All patients underwent computed tomography focusing on the integrity of the bony canal of the internal carotid artery and on the middle ear secretion confirmation. Exclusion criteria were obstruction of the ET in the nasopharynx, chronic suppurative otitis media, cleft palate, history of middle or inner ear surgery (other than tympanostomy), history of tuboplasty, head and neck cancer, pregnancy, consumption of anticonvulsants or antipsychotic medication, high risk of general anesthesia, or incomplete integrity of the bony canal of the internal carotid artery on computed tomography.
From among 40 eligible ears, 30 were included in the study (Fig. 1). Using random number generation, patients were assigned to BET only or BET with concurrent tympanocentesis.
Tympanometry, ability to perform a Valsalva or Toynbee maneuver with tympanometry verification, Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and pure-tone audiometry were used to evaluate the effect of BET. Tympanometry and audiometry were performed by an audiology assistant blinded to treatment type. Tympanometry was performed using a Madsen Zodiac tympanometer (Otometrics, Taastrup, Denmark). Regular tympanometry was performed first, followed by tympanometry after the Valsalva (first) and Toynbee (second) maneuver. Audiometry was performed in a soundproof cabin using a Madsen Orbiter 922 audiometer (Madsen Ltd., Budapest, Hungary) compliant with ISO 389 standards. Pure-tone audiometry was performed according to international standards (ISO 8253-1). The air-bone gap pure-tone average (AG-PTA) at 500, 1000, 2000, and 4000 Hz was determined during audiometry.
BET was performed in patients under general anesthesia with orotracheal intubation in the back position with slight head inclination and slight bow to the right. The procedure was initiated by decongestion of the nasal mucosa using nasal swabs with adrenaline at a dilution of 1:10,000. BET was performed using a commercial TubaVent set (Spiggle & Theis, Medizintechnik GmbH, Overath, Germany) consisting of a single-use insufflation pump and a catheter with a dilatation balloon at the end. The catheter was inserted into a metal inserter bent at 30 degrees at the end (Spiggle & Theis), and then transnasally introduced into the nasopharyngeal orifice of the ET and cartilaginous part of the ET under endoscopic control of a transnasally inserted rigid endoscope with high resolution (30 degrees, diameter 4 mm). The balloon was filled with saline to a target pressure of 10 bar using the insufflation pump. This pressure was applied for 2 minutes. Next, the saline was drained and the balloon pulled out of the nasal cavity, together with the inserter. In the case of bilateral OME, the same procedure was followed on the other side during anesthesia. New single-use material was used.
Tympanocentesis was performed before BET under a microscope (Opmi Vario 700, Carl Zeiss Meditec AG, Jena, Germany). It was performed in the anterior inferior quadrant of the tympanic membrane, and then the middle ear effusion was suctioned.
Data were recorded 1 day before surgery and 2, 6, and 12 months after the intervention.
Descriptive statistics, such as the arithmetic mean, standard deviation, and absolute and relative frequency tables, were used for data processing. Pearson's chi-squared test, paired samples t test, and Wilcoxon rank-sum test were used for comparisons among groups. The statistical tests were assessed using a significance level of 5%. Therapy was considered successful if there was a change in tympanogram B to tympanogram C or A, a newly acquired ability to perform Valsalva or Toynbee maneuver, or an improvement of the AG-PTA or ETDQ-7 score of 20% and more. The statistical analysis was performed using Stata 13 software (Stata Corp., College Station, TX).
A total of 30 ears (26 patients) with COME (19 right-sided and 11 left-sided) were included in the study: 15 underwent BET only (group 1) and 15 underwent BET with tympanocentesis (group 2). Compliance with follow-up was 96.7%. One ear in the BET only group was lost to follow-up after randomization. Thus, 14 ears in group 1 and 15 in group 2 were analyzed (Fig. 1). The BET only group had significantly more men. No differences were found between the groups in regards to age and presence of nasal polyps (Table 1). There were 13 (86.7%) patients with serous and two (13.3%) patients with mucoid middle ear effusion in the BET with tympanocentesis group.
No significant difference in improvement after treatment was found between the groups in any monitored parameter at any check-up during the 12-month follow-up (Table 2). There was great variability in the results (Figs. 2 and 3). In general, treatment was tolerated well. Five patients (three in group 1 and two in group 2) experienced mild (<3 on visual analogue scale) headaches that did not last more than 24 hours. All perforations from the tympanocentesis group healed without incident before the first follow-up examination. As no significant difference in treatment success was found between the two groups, patients were also evaluated as one group. After 2, 6, and 12 months, there was improvement in tympanometry in 55, 48, and 48%; in the ability to perform Valsalva or Toynbee in 55, 41, and 41%; in AG-PTA in 69, 62, and 59%; and in ETDQ-7 score in 76, 72, and 69%, respectively.
Even though BET appears to be a promising therapeutic option for ET dysfunction, data on its effect in patients with COME are still missing. There is also no clear conclusion on whether BET should be performed in combination with a procedure on the tympanic membrane in the case of COME. In most studies, an additional intervention on the tympanic membrane has been preferred (5–9). However, it is more empirical than an evidence-based procedure. One of the first to address this issue was Liang et al. (10). The conclusion of the study slightly favored BET with concurrent paracentesis before BET only, and both groups were superior to paracentesis only. This seems to be inconsistent with the results of our randomized clinical trial in which BET combined with concurrent tympanocentesis was not superior to BET only. However, only tympanograms and an unofficial scale for endoscopic findings were evaluated for 6 months in Liang's study, and they did not consider symptoms, hearing, or the ability to perform maneuvers. In addition, the only observed difference was in endoscopic findings 1 month after surgery. No significant difference was noted 3 and 6 months after surgery or in the tympanograms (10). Endoscopic findings alone may be associated with a risk of error because accurate assessment of the presence and quantity of middle ear effusion behind the tympanic membrane can be challenging. Therefore, if the results are analyzed in more detail, the previous study actually supports the results of our study (10). Taking into account the pathophysiology of OME, one-time aspiration of the middle-ear secretion should not logically play a crucial role, especially in the long-term. Therefore, considering that it has its own risks, concurrent tympanocentesis should not be routinely recommended. Longer time spent under general anesthesia must be taken into account as well. On the other hand, tympanocentesis confirms the diagnosis of COME.
The potential benefit of BET combined with the insertion of tympanostomy tubes still needs to be considered. Patients included in our study repeatedly underwent tympanostomy with only a temporary effect lasting until extrusion of the tube. We can only hypothesize the limited effect of tympanostomy considering medical history and the fact that patients did not benefit from tympanocentesis performed synchronously with BET. On the other hand, lower treatment success in both groups could still indicate that the effusion may not be adequately treated as it is not limited to the middle ear space and is percolating through the whole temporal bone. Therefore, it is still possible that BET combined with the insertion of tympanostomy tube could offer better outcomes. The consistency of the fluid in the middle ear could possibly impact outcome of therapy as well. However, we have only very limited data from the tympanocentesis group. The subgroups are too small and unequal to be validly analyzed. Further research is needed to solve these issues.
There are also insufficient data from which a clear conclusion can be drawn regarding the general success of BET in patients with COME, especially in the long-term. Therefore, one of the aims of our study was to provide data on the effect of BET in this group of patients. One of very few studies mentioning COME at least partly separately was Satmis and Van der Torn (11). In this study, the success of BET was evaluated in 14 ears. Improvement was observed in tympanometry in 74% after 3 months. Unfortunately, the results of other monitored parameters were no longer distinguished separately for the COME group. Williams et al. (12) reported an improvement in the tympanometric curve in 60% of ears. However, other parameters were not observed, and only five ears with COME were included. In contrast, Liang et al. reported improvement in tympanometry in 86% of 60 ears after 6 months (10). Patients in our study could also be evaluated as one group considering that lack of a significant difference in treatment success between groups. There was improvement in tympanometry in 48% of ears after 6 and 12 months and even lower if we evaluate the ability to perform Valsalva or Toynbee. On the other hand, improvement remained in air-bone gap and questionnaire score in almost 60 to 67% ears after 12 months. Even though we consider the ability to perform maneuvers to not be a robust indicator of ET function because the result is subordinate to the effort the patient put into it, the success of BET appears to be less in COME than in patients with other pathologies caused by ET dysfunction (5–9). This further decreases with length of follow-up.
Notably, the patients are themselves a control group, as only patients with COME not responding to at least one tympanostomy were included, and the next tympanostomy cannot be expected to offer any long-term improvement. There was no improvement in the 6 months period without treatment while patients waited for BET either. Therefore, BET (with or without tympanostromy) was significantly better compared with tympanostomy only or to no treatment. BET is certainly a benefit for patients with COME.
The main limitation of our study is sample size, which does not allow absolutely definitive conclusion. However, the prevalence of COME with no obstruction in the nasopharynx not responding to tympanostomy in adults is very low, and our cohort belongs to larger studies of this type. Another limit of our study could be the absence of an evaluation of treatment success by tubomanometry, which has gained popularity. On the other hand, some authors have not considered this examination to be appropriate because completely non-physiological pressures in the nasopharynx are used for measurement, and the results may not match the actual patient's status (13). In addition, tubomanometry only provides information on the condition at the time of measurement, which may not correspond with the long-term state of the ET.
It is necessary to mention that ETDQ-7 was used differently in our study. The questionnaire was validated for diagnostic of ET dysfunction using an optimal total item score cutpoint of less than 14.5 (14). However, the number of responders was relatively low and all types of ET dysfunction were originally evaluated together in one group. Therefore, ETDQ-7 may not always be completely accurate in diagnostic of all subgroups of ET dysfunction. It was observed in several patients with COME in our study, whose ETDQ-7 score was primarily physiological. However, the diagnosis of ET dysfunction is clear in case of COME with no obstructive pathology in the nasopharynx. In addition, the authors think that, e.g., the halving of significant difficulties can be considered a success and a great benefit for patient, but it still would have to be considered a failure, if ETDQ-7 score less than 14.5 was not reached. Therefore, a change in ETDQ-7 score was preferred to evaluate treatment effect rather than cutpoint score, the accuracy of which was recently questioned (15).
Supported by Ministry of Health, Czech Republic - conceptual development of research organization (FNOs/2016).
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