A Novel Diagnostic Tool for Chronic Obstructive Eustachian Tube Dysfunction The Eustachian Tube Score

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1 The Laryngoscope VC 2014 The American Laryngological, Rhinological and Otological Society, Inc. A Novel Diagnostic Tool for Chronic Obstructive Eustachian Tube Dysfunction The Eustachian Tube Score Stefanie Schr oder, MD; Martin Lehmann, MD; Odile Sauzet, PhD; J org Ebmeyer, MD; Holger Sudhoff, MD, PhD, FRCS, FRCPath Objectives/Hypothesis: The purpose of this study was to introduce a new tool for the diagnosis of chronic obstructive eustachian tube dysfunction (ETD) and as a follow-up tool for eustachian tube therapy using objective and subjective elements. Study Design: Combined, prospective, retrospective clinical study at a tertiary referral center. Methods: Physical examination, history, tympanometry, audiometry, and tubomanometry as well as the seven-item Eustachian Tube Dysfunction Questionnaire (EDTQ-7) were included as diagnostic tests. After initiating the eustachian tube score (ETS), we compared our results of healthy subjects to our data of patients with chronic obstructive ETD. In addition to ETS, an extended test ETS-7 was evaluated, which incorporated two additional items. Results: The test-retest reliability revealed a correlation of 0.82 for the ETS and 0.87 for the ETS-7. ETS-7 receiver operating characteristic analysis, with reference to the EDTQ-7 score, resulted in an area under the curve (AUC) of Our analysis considered essential criteria of ETD as comparative tools, which were typical clinical complaints, and at least two of three conditions: a pathologic EDTQ-7, a type B/C tympanometry, and a positive independent expert evaluation. The corresponding AUC was Chronic obstructive ETD was identified at a cutoff of 7, with a sensitivity of 96% and a specificity of 96%, using the novel ETS-7. Conclusions: ETS is a valid and reliable instrument in adult patients with chronic obstructive ETD. ETS-7, with a cutoff point of 7, should facilitate the diagnosis of ETD and might be valuable as a diagnostic follow-up tool. Key Words: Eustachian tube, tubomanometry, eustachian tube score, Eustachian Tube Dysfunction Questionnaire-7. Level of Evidence: 2b Laryngoscope, 125: , 2015 INTRODUCTION Pressure sensations in the ear, fluctuating hearing loss, or ringing in the ears are very common symptoms for a variety of middle and inner ear diseases. An obstructive dysfunction of the eustachian tube (ET) is one of the underlying possible causes of these symptoms. The ET is a narrow canal, of 31 to 38 mm in length, that connects the middle ear spaces with the nasopharynx. It consists of an osseous portion comprising the lateral one-third and a cartilaginous portion comprising the medial two-thirds. 1,2 Under regular conditions, the cartilaginous portion of the ET is closed and opens briefly for about 200 ms during swallowing, chewing, yawning, or From the Department of Otorhinolaryngology Head and Neck Surgery (S.S., M.L., J.E., H.S.), Bielefeld Clinical Center, Academic Teaching Hospital, University of M unster, Bielefeld; and the Department of Epidemiology and International Public Health (O.S.), Faculty of Health Sciences, Bielefeld University, Bielefeld, Germany. Editor s Note: This Manuscript was accepted for publication August 18, M.L., J.E., and H.S. received fees for sessions and financial support for research projects. O.S. received a reimbursement. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Holger Sudhoff, MD, Department of Otorhinolaryngology Head and Neck Surgery, Bielefeld Clinical Center, Teutoburger Str. 50, Bielefeld, Germany. holger.sudhoff@klinikumbielefeld.de DOI: /lary other jaw movements. The ET is responsible for pressure equilibration in the middle ear, and its dysfunction may lead to impaired sound transmission. Obstruction of the ET is a relatively common disorder that is not only uncomfortable but may also result in different middle ear pathologies such as chronic otitis media, tympanic membrane retractions, and cholesteatoma. Chronic obstructive ET dysfunction (ETD) has a prevalence of about 1% in the adult population. Forty percent of children under the age of 10 years develop at least temporary ET dysfunction. 3 Studies in children and adults demonstrate that ETD is present in up to 70% of patients undergoing tympanoplasty for chronic otitis media or cholesteatoma. 4,5 Most otologists agree that ET function is critical for the outcome of middle ear surgery. 6,7 It has always been difficult to identify sufficient diagnostic tools and tests as well as criteria to detect patients with ETD. 4 Distinguishing chronic obstructive ETD and a patulous ET is an additional challenge. Otoscopic evaluation of the tympanic membrane, Valsalva and Toynbee maneuvers, as well as pneumatic otoscopy are easily conducted but do not necessarily deliver reliable and quantifiable results. In clinical practice, usually a series of differing diagnostic tests are employed to narrow down the diagnosis. Supplementary tests, such as impedance measurements in the pressure chamber, require expensive equipment and do not yield any 703

2 TABLE I. The Eustachian Tube Score Facilitating Quantification and Interindividual Comparison of Eustachian Tube Function. Symptom/Finding 2 Points 1 Point 0 Points Clicking sound when swallowing Always Sometimes Never Positive subjective Valsalva Always Sometimes Never TMM 30 mbar 11,12 R 1 R> 1 No R TMM 40 mbar 11,12 R 1 R> 1 No R TMM 50 mbar 11,12 R 1 R> 1 No R Eustachian tube score ranging from 0 to 10 points. TMM 5 tubomanometry. specifically unique information. 3 Additionally, the majority of these tests only function with an intact tympanic membrane. Computed tomography (CT), cone beam CT, and magnetic resonance imaging (MRI), as well as slowmotion video endoscopy and sonotubometry, have so far not proven to be suitable for routine clinical practice Tubomanometry (TMM) was initially described by Estève in ,12 As a relatively simple method that allows assessment of ET patency under predefined conditions, taking a sip of water triggers the release of a defined pressure (e.g., 30, 40, and 50 mbar) through a nasal applicator. A pressure probe in the external auditory canal registers pressure changes transmitted though movements of the tympanic membrane or through a perforation in the tympanic membrane. Thus, TMM is a semiobjective method to record ET patency. Because objective measurements of tubal function are missing, we explored a simple and reliable test to narrow down the diagnosis of chronic ETD and assess the effectiveness of treatments such as the balloon dilatation eustachian tuboplasty (BET). 13,14 In the absence of a gold standard for the objective measurement of ET function and respecting the high relevance of subjective patient complaints, we tried to identify a tool that combines both subjective and objective elements for our novel approach. Any assessment should be suitable for use in daily routines. This means applying generally available methods and easily obtainable data. Considering these circumstances, we developed the Eustachian Tube Score (ETS) introduced in Validation of the ETS is presented and discussed. We expanded the ETS by adding two additional elements (ETS-7), which we introduce and evaluate. MATERIALS AND METHODS The ETS was introduced in 2010 in the context of a study on the outcome of BET. 15 The ETS score ranges from 0 to 10 points, 0 corresponding to no tubal function and the maximum score of 10 corresponding to highest tubal function (Table I). Thus, the ETS gives a quantitative assessment of ET function and allows interindividual as well as prospective comparison. TMM TMM was first described by Estève in ,12 The device was initially produced by La Diffusion Technique Francaise in Saint-Etienne, France, and is distributed by Spiggle & Theis, in Overath, Germany. The concept of TMM is the controlled delivery of defined pressures of 30, 40, and 50 mbar to the nasopharynx through a nasal applicator. The pressure is adjusted manually. We always perform the TMM using pressures of 30, 40, and 50 mbar. The whole procedure takes about 5 to 10 minutes depending on the experience of the operator. The pressure receptor probe is positioned in the ear canal, and the nasal applicator is positioned in both nostrils. Swallowing, for example, a glass of water triggers the pressure application. The recording starts automatically. Swallowing triggers the opening of the cartilaginous part of the ET. A pressure receptor probe located in external ear canal registers pressure changes transmitted though movements of the tympanic membrane/perforated tympanic membrane. If the ET opens during swallowing, the defined pressure applied to the nasopharynx is transmitted into the middle ear spaces. Pressure curves of the nasopharynx and the ear canal are displayed on the monitor of the TMM device, and various measuring values are calculated. Diagrams are created that measure the pressure changes in the nasopharynx and ear canal in millibars against the time in seconds (Fig. 1). The opening latency index (R value) reflects the latency between pressure application in the nasopharynx and measurement of a pressure change in the ear canal Fig. 1. Tubomanometry by Estève 11,12 showing pressure curves of the epipharynx and the external ear canal. (a) Immediate opening (R < 1) indicating regular eustachian tube (ET) function. (b) No opening (not measurable), indicating obstruction of the ET. (c) Patulous ET with fluctuation of the pressure curve in the external ear canal. 704

3 TABLE II. The Eustachian Tube Score-7 Facilitating Quantification and Interindividual Comparison of Eustachian Tube Function. Symptom/Finding 2 Points 1 Point 0 Points Clicking sound Always Occasionally Never when swallowing Positive subjective Always Occasionally Never Valsalva Objective Valsalva Immediate Weak and slow Negative Tympanometry A C B TMM 30 mbar 11,12 R 1 R> 1 No R TMM 40 mbar 11,12 R 1 R> 1 No R TMM 50 mbar 11,12 R 1 R> 1 No R Eustachian tube score-7 ranging from 0 to 14 points. TMM 5 tubomanometry. (R 5 P1 2 C1/C2 2 C1). P1 means the start of the movement of the ear drum after pressure application, C1 means the start of the pressure increase in the nasopharynx, and C2 means the reach of the maximum pressure increase in the nasopharynx. The R value quantifies ET patency: an immediate opening (R < 1) indicates good ET function; a late opening (R 1) indicates restricted ET function. A negative or not measurable R value indicates complete obstruction of the ET. 11,12 TMM is a semiobjective method to record and partially quantify ET patency. ETS The ETS contains three tubomanometric measurements and two subjective estimations of the patients concerning feasibility of Valsalva s and Toynbee s clinical symptoms. Positive Toynbee s clicking sound when swallowing and positive Valsalva s maneuver are rated with 0 points for never, 1 point for sometimes, and 2 points for always. The patients specifications are supposed to relate to at least the previous 2 months. TMM results at 30, 40, and 50 mbar are incorporated in the ETS as well. An immediate opening of the ET (R 1) is weighted with 2 points, a delayed opening (R > 1) yields 1 point, and no opening (negative or not measurable R) yields 0 points. Based on our preceding experience, we extended the ETS with two additional items. tympanometry and objective Valsalva, resulting in the ETS-7 (Table II). We aimed to increase its predictive value by using these additions. The objective Valsalva is weighted with 2 points for immediately positive, 1 point for only minimal and slow movement of the tympanic membrane, and 0 points for negative evaluation. The tympanometry is divided according to Jerger (Table III). 16 A curve type A yields 2 points, type C yields 1 point, and type B yields 0 points. Thus, the ETS-7 ranges from 0 to 14 points. Patient Selection We examined 215 healthy subjects (mean age 46 years, ranging from 16 to 89 years) with completely normal otological examinations between August 2011 and October Otoscopy, nasal endoscopy, tympanometry, audiometry (pure-tone audiometry, speech audiometry), and tubomanometry, as well as the ETS and ETS-7 were employed. The healthy subjects were volunteers without any past medical history of ear disease and surgery of the ear. The tympanic membrane was examined as normal in all included subjects. We compared our results of healthy subjects with data obtained from 171 patients (mean age 50 years, ranging from 14 to 81 years) with chronic obstructive ETD from 2009 to These patients showed type B or C curves in tympanometry and/or recurrent otitis media with effusion in the last 2 years and/or subjectively and objectively negative Valsalva clinical symptoms. Additionally, we compared the ETS and ETS-7 scores in two prospective subgroups. We collected data from 70 patients (mean age 47 years, ranging from 18 to 79 years) with chronic obstructive ETD. To define chronic obstructive ETD we used the following criteria: typical clinical complaints and at least two of three items: a pathologic seven-item Eustachian Tube Dysfunction Questionnaire (EDTQ-7), 17 type B or C curves in tympanometry, and expert judgment. Typical complaints were pressure sensations in the ear, problems with pressure equilibration in the ear, or fluctuating hearing loss. The EDTQ-7 is a validated instrument for the assessment of the function of the ET by the patient s history. We also collected prospective data from another 30 patients (mean age 43 years, ranging from 19 to 73 years) who presented with suspicion of a chronic obstructive ETD and typical complaints but failed the above-mentioned criteria. Assuming an incidence of 60% of chronic obstructive ETDs among the patients with typical complaints presenting at our department, and a sensitivity of 95% with 5% precision, 25 patients with a negative diagnostic and 38 with a positive diagnostic would be necessary for statistics. All subjects were informed about the use of all the collected data for clinical research and gave informed consent. To test the stability of the measurements, we obtained the ETS of 59 ears with chronic obstructive ETD (mean age 52 years, ranging from 19 to 78 years) and 50 ears of healthy subjects in multiple measurements in an interval of at least 1 week (mean age 32 years, range 17 to 52 years). Intraclass correlation coefficients (ICC) were obtained as measures of test-retest reliability using mixed models. Mixed models are regression models that take the nonindependence of measurements performed on the same patient, and the ICC is a measure of the average correlation between these dependent measurements over all patients. An ICC close to 1 indicates a very good reliability. The evaluation and comparison of the ETS-7 and ETS was performed using receiver operating characteristic (ROC) curves. This methodology consists of plotting true positive rates against false negative rates at various cut points to obtain the optimal threshold. The area under the curve is a measure of how well the score can discriminate between having a condition and not having it. A value of the area equal to 1 indicates perfect discrimination, whereas a value equal to 0.5 indicates no discrimination. In the absence of a gold standard for the diagnosis of chronic obstructive ETD, optimal cut points, and sensitivity and specificity, it was difficult to define patients as healthy or suffering from chronic obstructive ETD. As mentioned above, we decided to diagnose chronic obstructive ETD when typical complaints and at least two out of the following three items were positive: a pathologic EDTQ-7, 17 type B or C curves in tympanometry, and expert judgment. So far the only validated diagnostic tool for the assessment of chronic obstructive ETD is the EDTQ-7. Because of that we also compared the ETS and ETS-7 TABLE III. Tympanometry With Jerger Types. 16 Type Middle Ear Pressure, dapa Compliance A More than B Not measurable 0.5 C Less than

4 TABLE IV. ETS/ETS-7 in Healthy Subjects and Patients With Chronic Obstructive ET. 16 ET Score Healthy Subjects ETS, N Chronic Obstructive ETD ETS, n Healthy Subjects ETS-7, n Chronic Obstructive ETDETS-7, n (15.8%) 0 42 (12.3%) (12%) 0 24 (7%) 2 1 (0.2%) 54 (15.8%) 0 35 (10.2%) 3 3 (0.7%) 44 (12.9%) 0 37 (10.8%) 4 3 (0.7%) 49 (14.3%) 1 (0.3%) 50 (14.6%) 5 5 (1.2%) 27 (7.9%) 3 (0.8%) 29 (8.5%) 6 12 (3%) 31 (9.1%) 1 (0.3%) 36 (10.5%) 7 41 (10.1%) 18 (5.3%) 1 (0.3%) 31 (9.1%) 8 65 (16.1%) 14 (4.1%) 6 (1.5%) 24 (7%) 9 76 (18.8%) 8 (2.3%) 10 (2.5%) 11 (3.2%) (49%) 2 (0.6%) 21 (5.3%) 9 (2.6%) (12.6%) 6 (1.8%) (19.6%) 2 (0.6%) (14.1%) 6 (1.8%) (42.8) 0 Mean SD ET 5eustachian tube; ETD 5 eustachian tube dysfunction; ETS 5 eustachian tube score; ETS-7 5 seven-item ETS; SD 5 standard deviation. to the EDTQ-7, as it is the only available statistically tested instrument. All analyses were performed with Stata statistical software version 12 (StataCorp, College Station, TX). ROC analyses were performed using the Stata command roctab. RESULTS Subjects The mean age of the 215 healthy subjects was 46 years, and 66.5% were female and 33.5% male. The mean age of the 171 patients with chronic obstructive ETD was 50 years, and they were 45% female and 55% male. In the healthy cohort, an always-positive Valsalva was reported for 382 ears (88.8%), an only-sometimes positive Valsalva for 28 ears (7.6%). A negative Valsalva was reported in 10 ears (3.6%). In 240 ears (55.8%) the Toynbee test was consistently positive, in 58 ears (13.5%) occasionally, and in 132 ears (30.7%) the Toynbee test was negative. Otoscopy revealed normal findings in all of the healthy subjects, and the objective Valsalva was found to be positive in 82.9% and negative in 17.1% of the ears. Concerning tympanometry, 425 of 428 examined ears showed a type A and three ears a type B tympanometry. In the comparison group of patients with chronic obstructive ETD, the objective Valsalva was positive in 37.4% and negative in 62.6% of the examined ears. Tympanometry showed type A in only 9.1%, type B in 64.9%, and type C in 26% of the examined ears. Healthy subjects revealed an opening of the ET at 30 to 50 mbar in TMM in at least in 94%. The average R value always showed an immediate opening (R < 1). In comparison, the patients with chronic ETD showed an immediate opening of the ET at 30 mbar in 42% and at 50 mbar in 58%. The average of the R value was always a delayed opening (R 1). Not more than 45% of the ears showed an immediate opening in the 30 to 50 mbar range. Test-Retest Reliability The ICC for the repeated measurements of the 59 ears with chronic obstructive ET dysfunction of the ETS was 0.82, with an average of 2.7 measurements per person. For the 50 healthy ears it was 0.81, with an average of 4.5 measurements per person. The ICC for the repeated measurements of the ETS-7 for the 59 ears with chronic obstructive ET dysfunction was 0.87, with an average of 2.7 measurements per person. Discriminant Validity The ETS and ETS-7 were calculated for each ear in both groups. In about 83.8% of healthy subjects, an ETS-7 of 8 or more was found, and only 1.6% of the ears had an ETS-7 score of 4 or less. In comparison. the patients with chronic obstructive ETD had an ETS of 8 or more in only 7% and an ETS of 4 or less in 70.8% of investigated subjects. Regarding the ETS-7, about 89.1% of cases had an ETS-7 of 11 or more and only 1.7% of 7 or less. The patients with chronic obstructive ETD had an ETS-7 of 11 or more in only 4.2% of cases and an ETS-7 of 4 or less in 54.9% of cases. The result in both groups and the comparison of the ETS and ETS-7 are shown in Table IV. The ROC analysis of the ETS-7 score showed that with reference to the EDTQ-7 score, the area under the curve was 0.64 (0.48, 0.81), giving a diagnosis of chronic obstructive ETD for an ETS-7 7, with a sensitivity of TABLE V. Receiver Operating Characteristic Analysis of the Eustachian Tube Score-7 and Two of Three Criteria Positive: Pathologic Eustachian Tube Dysfunction Questionnaire-7, Tympanometry Type B/C, and Expert Judgment. Cut Point Sensitivity % Specificity % Correctly Classified %

5 Fig. 2. Receiver operating characteristic (ROC) analysis of the eustachian tube score. (a) Eustachian Tube Dysfunction Questionnaire-7 (EDTQ-7). (b) Two of three criteria positive: a pathologic EDTQ-7, tympanometry with type B/C, and expert judgment. 73% and a specificity of 60%. The analysis for the ETS showed an area under the curve of 0.67 (0.50, 0.84), giving a diagnosis of chronic obstructive ETD for an ETS 5, with a sensitivity of 72% and a specificity of 53%. We also performed an ROC analysis of the ETS-7 score with reference to the criteria: typical complaints and at least two of three items: a pathologic EDTQ-7, 17 tympanometry with type B or C curves, and expert judgment. It showed an area under the curve of 0.98 (0.95, 1) giving a diagnosis of chronic obstructive ETD for the ETS-7 7, with a sensitivity of 96% and a specificity of 96% (Table V). The same analysis for the ETS showed an area under the curve of 0.91 (0.87, 1) giving a diagnosis of chronic obstructive ETD for an ETS 5, with a sensitivity of 91% and a specificity of 86%. The ROC analyses of the ETS and ETS-7 are presented in Figures 2 and 3. DISCUSSION Chronic obstructive ETD has regained the attention of otologists over the past years. It is generally acknowledged that the ET has a major impact on the outcome of middle ear surgery and plays a pivotal role in the pathogenesis of otitis media with effusion and cholesteatoma. The effective treatment options for chronic obstructive ETD as well as diagnostic tools were virtually nonexistant. 18 In 2009, we developed the new therapeutic approach of BET. More than 1,075 procedures for chronic obstructive ETD have been performed in our department. 19 In this context, we were confronted with the lack of sufficient diagnostic tools for the assessment of ETD. We investigated a simple but reliable and valid instrument to delineate the indication of BET and to use as a follow-up tool. Our preliminary investigations of TMM 20 and the ETS, 15 introduced in 2010, revealed a significant correlation between the results of different investigators and different times of investigation. Therefore, we continued to pursue this novel approach. To increase the positive predictive value we integrated more objective data. We decided to include simple clinical examinations, such as the objective Valsalva in the novel ETS-7. A positive Valsalva and Toynbee maneuver is a solid indicator for the patency of the ET but not necessary for normal function. 10 Tympanometry results are another important aspect. This method was kept simple and available to Fig. 3. Receiver operating characteristic (ROC) analysis of the eustachian tube score-7. (a) Eustachian Tube Dysfunction Questionnaire-7 (EDTQ-7). (b) Two of three criteria positive: a pathologic EDTQ-7, tympanometry with type B/C, and expert judgment. 707

6 the majority of ear, nose, and throat specialists. Unfortunately, it only allows indirect conclusions concerning the mobility of the tympanic memebrane. 10 Tympanometry can only give a temporary insight under ambient pressure conditions. A significant number of patients complain about problems with pressure equalization during diving or flying. Another group exhibits recurrent otitis media with effusion with consistent symptom-free intervals. in these patients especially, past medical history is essential and helpful. It was therefore obvious to combine subjective and objective tests for a predictive projection of ET function in the absence of any gold standard. The ETS and ETD-7 are brief and easy tools to complete with widely available methods. Both have demonstrated reliability and validity for adults. Our investigations showed that the validity of the ETS-7 is superior to the ETS. But the ETS is a good diagnostic option in patients with perforated ear drums, because it does not contain objective Valsalva criteria and tympanometry. One of the most important limitations of our study is the problem of precisely separating patients with chronic obstructive ETD from those with clinically similar complaints. A gold standard for the diagnosis of a chronic ETD is missing. For the evaluation of the ETS and ETS-7, we decided to assume a chronic obstructive ETD when at least two of three criteria were positive. Both the ETS and especially the ETS-7 yielded promising results. There are abundant methods for the assessment of ET function, such as the Nine-Step-Inflation- Deflation-Test, CT or MRI, sonotubometry, tensometry, or pressure chamber measurements. 3,4,10 None of them is suitable for routine application. The EDTQ-7, a novel and promising ET assessment questionnaire, was introduced by McCoul and coworkers in Our current investigations confirmed it as a sufficient, reproducible, and valid instrument in assessing ETD. 21 However, it only assesses the patient s subjective complaints and does not consider objective evaluation. CONCLUSION The ETS-7 is a valuable instrument for outcome measurement and follow-up of patients with ETD and an intact ear drum. The ETS is recommended for the assessment of chronic obstructive ETD in patients with grommets or perforated ear drums. The ETS and the ETS-7 are valid and reliable instruments in adult patients with chronic obstructive ETD. Both seem suitable for ET research. Future investigations of ETS and ETS-7 comprising larger patient cohorts are desirable. Based on our findings, we suggest a cutoff at 7 for defining ETD when employing the ETS-7 and 5 for defining ETD when employing the ETS. BIBLIOGRAPHY 1. McCoul ED, Lucente FE, Anand VK. 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