There are few treatment options for patients with persistent Eustachian tube dysfunction (ETD). Balloon dilation of the Eustachian tube (ET) has been suggested as a possible treatment, but until recently, randomized controlled trials had not been conducted to validate its efficacy (1,2). We recently published results of a randomized controlled trial of balloon dilation versus medical management for the treatment of ETD (1). The results demonstrated the safety and superior efficacy of balloon dilation over medical management through 12-month follow-up. Because there is a paucity of literature on treatment efficacy beyond 12-months, we extended the long-term follow-up of the participants who had undergone balloon dilation in the randomized trial.
MATERIALS AND METHODS
Study Design and Population
This is an extended single-arm follow-up protocol from a previously reported prospective, multicenter, randomized controlled trial comparing balloon dilation to continued medical therapy (control) in patients with persistent ETD (1). This study extension was approved by an Institutional Review Board for each participating site and all participants signed informed consent.
Methods of the randomized controlled trial have been detailed previously (1). Briefly, participants were required to be 18 years or older, diagnosed with ETD for more than or equal to 12 months, have three or more ETD symptoms, have an Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score of 3 or higher (3), and be refractory to medical therapy. Exclusions included patulous ET, uncontrolled chronic rhinosinusitis, allergies, or reflux, and ear tubes or perforated tympanic membranes at enrollment. Ten nonrandomized participants who were part of the roll-in pilot phase were also eligible to participate in the long-term follow-up. These roll-in participants received balloon dilation and enrollment criteria and follow-up were similar to the randomized cohort.
Participants were randomized to balloon dilation with the XprESS device (Entellus Medical, Plymouth, MN) or continued medical management. After 6 weeks, control participants who did not demonstrate improvement in symptoms (ETDQ-7 < 3.0) were allowed to crossover to balloon dilation. Control participants who were not eligible or chose not to crossover were exited from the study. All balloon dilation participants (roll-in, randomized, or crossover) were followed for 12-months under the original protocol. To be eligible for the long-term extension study, participants had to have undergone balloon dilation and completed the 12-month follow-up for the original protocol.
From August 2017 to October 2, 2018, long-term follow-up visits were conducted for all participants at 6-month intervals based on the date of their index procedure. The follow-up assessments included: ETDQ-7 and middle ear functional assessments (tympanogram, tympanic membrane position, and Valsalva maneuver). Data were collected for revision dilation procedures and other ETD-related ear surgeries. Participants were surveyed to determine whether they were satisfied with the procedure outcome and whether they would recommend it to friends or family.
We used the validated ETDQ-7 to evaluate changes in participant symptoms (3). This patient-report questionnaire evaluates the severity for 7 ETD-related symptoms (pressure, pain, feeling clogged, cold/sinusitis problems, crackling/popping, ringing, and muffled hearing) on a scale of 1 (no problem) to 7 (severe problem). A mean of the item scores is calculated to produce the overall score. Scores of 1 to 2 indicate no to mild symptoms, 3 to 5 indicate moderate symptoms, and 6 to 7 indicate severe symptoms.
Otoscopy was used to determine the tympanic membrane position (normal or retracted). A change from retracted at baseline to normal at follow-up was considered an improvement. Improvement in Valsalva maneuver was defined as a change from negative at baseline to positive Valsalva at follow-up. Tympanometry normalization was defined per side as a change from type B or C at baseline to type A at follow-up.
Revision dilations and other ETD-related surgical procedures were noted during follow-up. Revision dilation was defined as any repeat balloon dilation procedure performed on an ET that was treated with balloon dilation in the original study. Other ETD-related surgeries were defined as procedures that were undertaken to address persistent or recurrent ETD symptoms on a Eustachian tube that was initially treated with an XprESS device.
Categorical variables were summarized by frequency and percentage. Continuous variables were summarized by mean and standard deviation (SD). Changes from baseline to follow-up were compared using 2-sided paired t tests for continuous measures and McNemar's or Bowker's tests for categorical measures. Values of p < 0.05 were deemed statistically significant. All statistical analyses were performed with SAS software Version 9.4 (SAS Institute, Inc., Cary, NC). The statistical analysis was performed by an independent statistician (LT).
To evaluate potential selection bias, a sensitivity analysis was performed to compare the change from baseline to 12 months in overall ETDQ-7 scores of the initial study participants who did not participate in the long-term follow-up with those participants who did participate in the long-term follow-up. The change from baseline to 12-month follow-up for overall ETDQ-7 scores was not significantly different between the groups (p = 0.165).
Fifty-eight participants from the initial study were eligible for enrollment in the long-term follow-up study (49 randomized or crossover participants and nine roll-in participants). A total of 47 participants (representing 83 treated ETs) were enrolled in the long-term follow-up study. The mean (SD) time to last follow-up was 29.4 (6.5) months (range, 18–42 mo). Baseline characteristics are shown in Table 1.
Participants symptoms were significantly improved with the mean overall ETDQ-7 score reduced from 4.5 ± 0.8 at baseline to 2.0 ± 1.0 at last follow-up (change –2.5; p < 0.0001) (Table 2). Furthermore, 93.6% (44/47) participants had a reduction of one or more in their overall ETDQ-7 score at their last follow-up visit. Each ETDQ-7 item score was significantly reduced (p < 0.0001) with changes ranging from –1.7 for ringing in the ears to –3.1 for feeling of clogged ears (Fig. 1).
One participant underwent a revision ET dilation at 362 days after the index dilation. The ET revision was performed concurrently with balloon dilation for recurrent sinus disease. There were no other ETD-related surgeries during the long-term follow-up period.
Changes in middle ear functional assessments demonstrated significant improvement. Overall, tympanic membrane position improved from 46.8% of participants within normal limits at baseline to 85.1% (p < 0.0001) within normal limits at the last follow-up. Ability to clear the ears with a Valsalva maneuver improved from 28.3% of participants at baseline to 73.9% (p < 0.0001) at the last follow-up. The percent of ears with type A tympanograms increased from 70.0% at baseline to 86.3% (p = 0.005) at the last follow-up.
In the subgroups of participants who had abnormal middle ear functional assessments at baseline, significant improvements were experienced at the last follow-up visit (Table 2). Tympanic membrane position was normalized in 76.0% participants (p < 0.0001), Valsalva maneuver was positive in 66.7% participants (p < 0.0001), and tympanogram type was normalized in 62.5% ears (p < 0.001). These values are consistent with the outcomes observed at 12-months follow-up.
Table 2 also presents the satisfaction survey results demonstrating high rates of satisfaction and willingness to recommend the procedure.
We previously reported the randomized outcomes of this study and follow-up through 12 months. Here, we report on outcomes for participants from the previous study, now with a mean follow-up of over 2 years after balloon dilation for persistent ETD.
Over a mean of 29 months follow-up, balloon dilation participants maintained the initial significant improvements over baseline using ETDQ-7 scores for symptoms severity and standard middle ear assessments. The results of the current study are consistent with the results previously reported by us (1). Another recently published randomized controlled trial that followed participants through 6-months also showed very similar results to ours for symptom improvement as well as middle ear assessments (2).
The ETDQ-7 was developed in 2012 (3,4) and has been gaining popularity for evaluating changes in ETD symptom severity (5–9). To our knowledge, this study provides the longest follow-up of prospectively collected ETDQ-7 scores in patients after ET balloon dilation.
The strengths of the study include extended follow-up of a prospectively enrolled cohort of patients and use of standardized and validated outcomes. Limitations of this study include the lack of a control beyond 6 weeks follow-up and the lack of participant blinding. The crossover design meant that there was no control arm to compare outcomes beyond the 6-week period, so it is unknown how many participants may have had resolution of their ETD symptoms beyond that period without intervention. However, the inclusion criteria were designed to ensure enrollment of participants with long-standing, persistent ETD who had already failed medical management. At 6-weeks, only one out of 27 control participants (3.7%) did not qualify for the crossover due to symptom resolution. Therefore, we think it to be very unlikely that any significant number of participants would have had symptom resolution without intervention such that these long-term results would lack clinical meaning. Participant blinding was not feasible since most of the procedures were performed in the office setting under local anesthesia. However, the consistency of repeated validated subjective and objective outcome measures over an extended period suggests a limited placebo effect. The insignificant change in mean ETDQ-7 score observed in our randomized control group at 6-weeks follow-up (–0.6) (1) was similar to the insignificant changes observed for a recent blinded study comparing placebo and active inferior turbinate reduction treatments for patients with ear symptoms (–0.7) (10); thereby, indicating that the difference we observed between the control and balloon dilation was real.
There is no standard single test that is diagnostic for Eustachian tube dysfunction and middle ear assessments may be normal in patients experiencing chronic symptoms (11). Combinations of functional tests with patient symptomology may provide more accuracy than any single test alone (12,13). Therefore, we did not require participants to have abnormal tympanograms at baseline. However, in addition to chronic symptomology and an abnormal baseline ETDQ-7, 84% of our participants had abnormal baseline findings in one or more of the following assessments: tympanogram, tympanic membrane position, Valsalva maneuver, and previous placement of tympanostomy tube. We think that our study population is representative of patients who may benefit from Eustachian tube balloon dilation.
Participants, who were followed for a mean of 29 months after balloon dilation, demonstrated significant reduction in the mean overall ETDQ-7 score compared with baseline. Middle ear assessments were also significantly improved at the long-term follow-up period. Eustachian tube balloon dilation results in a long-term improvement for patients with persistent ETD.
The authors wish to thank the study investigators and coordinators: Rodney J. Schlosser, M.D., Zachary M. Soler, M.D., Mark J. Hoy, M.D., Habib G. Rizk, M.D., Theodore R. McRackan, M.D., and Christopher F. D’Esposito, B.S., Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina; Roger J. Simpson, M.D., and Brooke Luenenborg, PA-C, Ear Nose Throat and Sinus Clinic, LLC, North Platte, Nebraska; Michael J. Clark, M.D. and Irmgard Lewis, Donald Guthrie Foundation, Sayre, Pennsylvania; Andrew Clark, P.A., Austin Ear Clinic, Austin, Texas; and Diana McClernon, Colorado Sinus Institute, Denver, Colorado.
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