Ph.D.-Project: Eustachian Tube Dysfunction: Causes, Diagnosis, Treatment, and Prognosis

Specific Aims:

Translation, modification, and validation of the ETDQ-7 in Danish settings Investigation of combined Cone-Beam CT and MRI of the Eustachian tube in order to determine a potential anatomical cause/disposition of ETD Clarification of the effects of BET using strict criteria for ETD To validate the process of tubomanometry as an objective tool in patients with ETD

Hypothesis

ETDQ-7 is a useful patient-reported symptom scoring tool in Danish patients with assumed ETD ETD is related to the dimensions and angles of the Eustachian tube detected by combining Cone-Beat CT and MRI-scans BET is effective in patients with chronic ETD Tubomanometry can be used as an objective tool in diagnosing and monitoring the effect of treatment in patients with ETD.

Study 1:

Danish translation, modification, and validation of the Eustachian Tube Dysfunction Questionnaire Holm NH1 \& Ovesen T1.

1. ENT Department, Regional Hospital West Jutland, Expected publication in Clinical Otolaryngology

The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was introduced in 2012 by McCloud et al. It scores symptoms of ETD, and it is the only validated patient-reported scoring tool. So far, ETDQ-7 has been translated and validated into German, Turkish, and Brazilian Portuguese. The aim of the present study is to translate, modify and validate the questionnaire in Danish settings to achieve a solid tool for optimal diagnostic and evaluation of treatment among patients with ETD.

Back and forth translation from English to Danish will be performed by a professional translator. Then, a modification/cultural adaption of the questionnaire will be conducted. Seventy-five patients older than 18 years referred to practicing ear nose and throat specialists will be included. Inclusion criteria are symptoms of ETD for more than three months including tympanometry compatible with negative middle ear pressure (C2 or B-curve). The seven questions in the ETDQ-7 are: 1) pressure in the ears, 2) pain in the ears, 3) a feeling that the ears are clogged or "under water", 4) ear symptoms when having a cold or sinusitis, 5) crackling or popping sound in the ears, 6) ringing in the ears or 7) feeling that the hearing is muffled. Patients will fill out the questionnaire before and after tympanostomy (insertion of ventilation tubes). Patients will then be referred to the ENT Department, Regional Hospital West Jutland for further follow up, including controlling the tympanostomy tubes. Here, a complete oto-rhino-laryngological examination, fiber optic naso-pharyngo-laryngo-scopy, pure tone audiometry, and tympanometry will be performed. SNOT-22 questionnaire is completed for differential diagnostics. Results will be compared to 75 age- and gender matched controls with no history of ETD or ear-surgery. In addition, patients undergoing BET will complete the questionnaire before and after surgery.

For test-retest data, 15 patients and 15 controls repeat filling out the questionnaire 14 days after the first reply. Patients are excluded from the retest in case of upper airway infection or travelling by airplane between the two tests. By comparing these results and calculating the Spearman's rank correlation coefficient, the test-retest reliability of ETDQ-7 is assessed. The internal consistency of the questionnaire will be investigated by using Cronbach's alpha coefficient and Spearman rho. Hence, it will be possible to conclude if ETDQ-7 can be used as a diagnostic tool to differentiate patients with ETD from individuals without ETD as well as to evaluate the effect of BET.

Study 2:

Cone-Beam CT combined with MRI as a diagnostic tool in patients with Eustachian Tube Dysfunction Holm NH1, Ovesen T1, Balazs M2 \& Pedersen M3

1. ENT Department, Regional Hospital West Jutland
2. Department of Radiology, Regional Hospital West Jutland
3. Institute of Experimental Clinical Research, Aarhus University Hospital Expected publication in Otology and Neurotology

The Eustachian tube (ET) is both skeletal and cartilaginous in nature. CT and/or MRI are often used preoperatively to identify potential pathology in the temporal bone. However, these techniques are not routinely used in order to diagnose ETD. It is unclear whether ETD is associated pathology in the skeletal or cartilaginous regions of ET. Length, diameter and/or angle of the ET may be a potential anatomical explanation for ETD, alternatively a disposition of ETD.

Cone-beam computed tomography (CBCT) is a relatively new imaging technique, where divergent X-rays form a cone. CBCT can accurately visualize the facial bones, and is often used by dentists and orthodontics. A study has shown no difference in the temporal bone between patients with patulous Eustachian tube and a control group. No other study has investigated ETD patients with CBCT. The cartilaginous part of ET is ideally visualized with MRI, whereas CBCT is the best choice for the skeletal part. Both MRI and CBCT are therefore needed in order to obtain a complete overview of ET. By implementing a brand-new software technique, MRI and CBCT sequences will be fused. This will enable a better visualization of the ET, where the length, diameter and angle of ET can be measured more accurately than with the current available methods. Thus, dimensions of the ET in ETD patients can be classified accordingly to normal dimensions of ET.

To achieve this, twelve patients with ETD and 12 healthy controls are examined with both MRI and CBCT. The sequences will be fused and two radiologists will describe the scans blinded and independently. The dimensions and angulations of the ET in the two groups are compared to identify significant differences.

Study 3:

Balloon Eustachian Tuboplasty: indications and effect of treatment Holm NH1, Ovesen T1 \& Sinkkonen ST2) 1) ENT Department, Regional Hospital West Jutland 2) Department of Otorhinolaryngology, Head and Neck Center, Helsinki University Hospital, Finland Expected publication in The Journal of Laryngology \& Otology

Patients with long-lasting symptoms of ETD, who benefits from tympanostomy tube insertion, will be offered Balloon Eustachian Tuboplasty (BET) of the cartilaginous part of ET. The procedure is performed endonasally under general anesthesia. It is believed that BET leads to micro-bleeding in the mucosa with subsequent scarring and expansion of ET. Apparently, the procedure has a high success rate and low complication rate. Currently, little evidence exists regarding the long-term effects of BET, and it remains unclear which patients will benefit from the procedure.

The aim of this study is to create a national cohort where all patients undergoing first time BET in Denmark, are registered. A REDCap-database is established. All patients are followed for 12 months by ETDQ-7, oto-microscopy and tympanometry. The patients, who benefit from the procedure, will be compared to those without effect. Hence, the investigators hypothesize that it will be possible to assess which factors increase the probability of effect from BET in order to select patients for BET more accurately in the future.

Study 4:

Tubomanometry: an objective tool in diagnosing patients with Eustachian Tube Dysfunction Holm NH1, Ovesen T1 \& Sudhoff H2

1. ENT Department, Regional Hospital West Jutland. 2) Klinikum Bielefeld, Head and Neck Surgery

Tubomanometry (TMM) was introduced in 2009 as an objective tool to measure the dynamic function of ET. While swallowing a small amount of water, a standardized air-pressure is applied through a nasal catheter. If the ET opens, pressure will be transferred to the middle ear cavity and the increased pressure will be measured with a probe in the ear channel. The test is harmless, relatively fast, and can be used even in case of perforation of the tympanic membrane or tympanostomy tube. In a control group, Schröder et al found an opening of ET in 97 %, opposed to 57 % in a group of ETD-patients. Another study showed that TMM has a high sensitivity, but low specificity for detecting ET opening. A reduced opening/lack of opening of ET is associated with ETD. Schilder et al concluded, that the existing evidence is weak, which is partly because of the disparate definitions of ETD. Finally, there is now consensus both internationally and in Denmark on definitions of ETD. Therefore, the investigators hope to develop new knowledge in an effort to develop a globally acceptable definition of ETD.

The investigators aim at examining 50 patients with ETD and compare them to 50 age- and gender matched controls to investigate TMM's ability to distinguish the two groups. The investigators believe that TMM has a great potential and most likely relates to the pathological process of the disease. It may be a useful tool in direct testing of the ET and monitoring the effect of treatment of ETD.