To determine the clinical effectiveness of interventions for adult Eustachian tube dysfunction (ETD) and to identify gaps in the evidence.

Both published and unpublished literature will be identified from systematic searches of electronic sources, hand searching, consultation with experts in the field, and reference checking. The following databases will be searched: MEDLINE, MEDLINE In-Process, Cumulative Index to Nursing & Allied Health (CINAHL), EMBASE, Science Citation Index, BIOSIS, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, Cochrane Central Register of Controlled Trials (CENTRAL), PASCAL, and Latin American and Caribbean Health Sciences (LILACS). In addition, information on studies in progress, unpublished research or research reported in the grey literature will be sought by searching a range of relevant databases including Conference Proceedings Citation Index: Science, Inside Conferences, Dissertation Abstracts, ClinicalTrials.gov, Controlled Clinical Trials, WHO International Clinical Trials Registry Platform portal, EU Clinical Trials Register, National Research Register Archive, US Food and Drug Administration (FDA), UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

The strategy combines terms for Eustachian tube and terms for interventions used to treat ETD. No language or date limits will be applied to the search strategy and study design filters will not be used.

The review will include experimental trials (randomised and quasi-randomised) as well as observational studies with a control group. Uncontrolled observational studies (e.g. case series) including at least 10 patients will also be considered for interventions where no controlled studies are found. Studies without a control group have considerable limitations, particularly where the condition may naturally resolve and where there are limited data available on the natural history of the condition. This study design will be included to provide as broad an overview as possible of current research in this field and in order to help inform any recommendations for future research. Only English language studies will be included.

The Eustachian tube is a narrow tube which links the back of the nose to the middle ear. It is normally closed but opens when we swallow, yawn or chew. The Eustachian tube has three main functions: to protect the middle ear from pathogens; to ventilate the middle ear, which can help to keep the air pressure equal on either side of the eardrum, enabling the eardrum to work and vibrate properly; and to help drain secretions from the middle ear cleft.

Eustachian tube dysfunction (ETD) is the inability of the Eustachian tube to adequately perform these functions. However, the precise function and mechanisms of the Eustachian tube and the underlying causes of dysfunction are complex and not fully understood.

Adults (18 years or older) with a clinical diagnosis of ETD will be included. Given the current lack of consensus on diagnostic criteria for ETD, a strict definition of ETD will not be applied and primary study definitions of ETD will be accepted, provided that they are based on symptomatology, and/or tests such as tympanometry or otoscopy. Studies of patients with known patulous Eustachian tube or nasopharyngeal tumours will be excluded as these populations are distinct and are likely to require different management options. Studies with mixed populations of patients with and without ETD will be included if separate outcome data are available for the population of interest.

Controlled studies with mixed populations of adults and children which do not report separate outcomes data for adults, or controlled studies that do not specify whether the whole study population were adults will be included.

Interventions explicitly aimed at treating ETD will be eligible. Eligible interventions will include: active observation (monitoring to determine whether the condition resolves naturally); supportive care (e.g. advice on self-management strategies such as advice to swallow, yawn, or chew); auto-inflation (e.g. Valsalva manoeuvre); nasal douching, topical nasal decongestants (e.g. Xylomethazoline); antihistamines (e.g. Clemastine); intranasal corticosteroids (e.g. Fluticasone propionate, Budesonide, Mometasone); oral corticosteroids (e.g. Prednisolone); leukotriene receptor antagonists (e.g. Montelukast, Zafirlukast); antibiotics (e.g. Doxycycline); simethicone (e.g. Gas-X); surgery (e.g. pressure equalisation tubes, balloon dilatation of the ET, transtubal application of fluids, laser Eustachian tuboplasty).

Any comparator (placebo, no intervention or another eligible treatment) will be considered for inclusion.

Primary, secondary and tertiary care.

Primary outcomes

There is currently no consensus regarding the most appropriate measure of treatment success. Change in severity and/or frequency of symptoms will be treated as the primary outcome as this is likely to be relevant to patients.

Secondary outcomes

Other outcomes of interest will include: quality of life; improvement in middle ear function based on measurements tools such as tympanometry (reported as a categorical or continuous outcome); improvement in hearing based on audiometry (reported as a categorical or continuous outcome); tympanic membrane mobility; clearance of middle ear effusion; need for additional treatment , e.g. requirement for surgical procedure (including re-intervention); early tube extrusion (for pressure equalising tubes); adverse events of interventions; and complications related to ETD (e.g. atelectasis).

Data relating to study design, population characteristics, inclusion criteria (including method of diagnosing ETD), intervention and comparator, details of outcome measures used and results will be extracted by one reviewer using a piloted and standardised data extraction form. Dichotomous outcomes will be extracted as relative risks and continuous outcomes as mean differences (with 95% confidence intervals). We will record whether studies present outcome data by participants or by ear. Extracted data will be independently checked for accuracy by a second reviewer. Disagreements will be resolved through consensus, and if necessary, a third reviewer will be consulted. Authors will be contacted for clarification and missing data as necessary. Data from studies with multiple publications will be extracted and reported as a single study.

RCTs will be assessed using the Cochrane Risk of Bias Tool. Tools used in previous reviews will be adapted and employed for the assessment of comparative non-randomised studies and the assessment of case-series. The assessment will be performed independently and in duplicate by two reviewers. Disagreements will be resolved through consensus, and, if necessary, a third reviewer will be consulted.

In the first instance, study characteristics and quality assessment will be presented in a series of structured tables. We anticipate that it is unlikely that there will be sufficient data available for a quantitative synthesis or sophisticated subgroup analysis. If this is the case a narrative synthesis will be undertaken, with studies grouped by intervention and then outcome and duration of follow-up. Results will be interpreted in the context of the quality of the individual studies and clinical heterogeneity. Where there are sufficient clinically homogeneous data, data will be pooled and statistical heterogeneity will be investigated using appropriate methods. Should a quantitative synthesis be possible, an analysis plan will be specified prior to undertaking any analysis to reduce the risk of introducing bias.

Analysis of specific subgroups will be undertaken where sufficient data are available. Key characteristics of interest are definition of ETD used, duration of ETD, associated conditions and severity of ETD symptoms at baseline.

Dr Catriona McDaid

Centre for Reviews and Dissemination

University of York

York, UK

YO10 5DD

catriona.mcdaid@york.ac.uk

Centre for Reviews and Dissemination (CRD)

http://www.crd.york.ac.uk

Ms Melissa Harden, CRD
Mr Alexis Llewellyn, CRD
Dr Catriona McDaid, CRD
Dr Gill Norman, CRD

Mr Andrew Coatesworth, York Foundation Trust
Professor Anne Schilder, University College London Partners
Dr Daniel Kimberling, Gale Farm Surgery, York

08 October 2012

29 March 2013

National Institute for Health Research (NIHR). HTA No. 12/43/01

None known

National Institute for Health Research, HTA No. 12/43/01

English

England

Subject indexing assigned by CRD

Eustachian Tube; Humans; Drug Therapy; Otorhinolaryngologic Surgical Procedures

12 October 2012

03 January 2013