Title: An evaluation of the High Frequency Digit Triplet test as a screening tool for early detection of hearing loss in individuals with cystic fibrosis
Funder: Department of Health and Social Care

Abstract: Background: Cystic fibrosis (CF) is the commonest life-limiting, autosomal recessive disorder in the UK, affecting 9000 people(1). Patients frequently receive repeated and prolonged courses of aminoglycoside antibiotics (which are ototoxic), to treat chronic pulmonary infection with Pseudomonas aeruginosa. This confers a high risk of permanent, bilateral, sensorineural hearing loss. The risk of hearing loss with one course of intravenous aminoglycoside is around 1.7%(2). However, patients with CF commonly receive 4 courses of aminoglycosides per year, often from a young age. We estimate that the prevalence of hearing loss in UK CF patients is 27%(3). There is a need for a simple screening test which will identify those patients in whom aminoglycosides should be avoided. Research questions: Does the High Frequency Digit Triplet test (HFDT test) accurately identify stable CF patients who should have a formal audiogram to detect hearing loss? Can the test be used in sick patients prior to intravenous antibiotics? Can the test be used in children of primary school age? Plan of investigation: Young people and adults with CF (11 years and over) will be assessed with both the HFDT test (screening test) and the standard pure tone audiogram (PTA). Patients will also have tympanometry, to detect any conductive hearing loss, which has a different aetiology. The PTA and tympanogram will be undertaken by a research fellow (trained by an audiologist). Work stream 1. The tests will be performed at any clinic visit when the patient is stable (patients are seen 6 times per year). Patients with CF commonly have an &ldquo;annual assessment&rdquo; and if the HFDT test proves feasible and valid, it could in future be performed as part of this assessment. Work stream 2. The tests will be performed when the patient is admitted for intravenous antibiotics. This will evaluate whether the HFDT test is a suitable screening test in patients who are unwell with respiratory symptoms. Hearing may deteriorate rapidly and so a previous test may no longer be reliable. Work stream 3. The HFDT test will be evaluated for feasibility and validity in primary school children aged 10 to 5 years. We will test 11 children with CF in each age group and compare with 12 healthy controls. The control participants will determine whether any poor performance of the HFDT test is a feature of CF (eg due to cough) or whether it is due to age. Potential benefits: If the screening test is effective, we will apply for further funding to evaluate its use, via the internet, in the home. If this is feasible and valid, we will offer it to every CF patient in the UK, over 5 years. We estimate the prevalence of hearing loss in CF is 27%. Currently, the only routinely available hearing test is the PTA and it is not possible to perform this in all at risk patients. Cost of PTA = &pound;95. There are 8259 UK CF patients >3y(1). Therefore total cost of PTAs for all at risk patients would be &pound;785,000 per annum. If only 27% of patients require a confirmatory PTA following screening with the HFDT test, then the cost of performing PTAs in UK CF patients would be &pound;211,950. (This is a saving of &pound;573,050 compared with a PTA in all at risk patients.) We have included 10 days of health economic consultancy time in this application to test these assumptions (see below under importance to public, patients and the NHS" and under "expected output of research")."

Lay abstract: Cystic fibrosis (CF) is an inherited condition which affects 9000 people in the UK, over half of whom are adults. Life expectancy is around 40 years, but is increasing steadily, largely due to improved treatment of chronic lung infections. However, treatment over many years with some antibiotics (&ldquo;aminoglycosides&rdquo;) may have toxic effects, including permanent and severe hearing loss, usually affecting both ears. Even mild hearing loss has a damaging effect on schooling and future employment prospects. The conventional hearing test &ndash; the pure tone audiogram &ndash; must be performed by an audiologist, using specialised equipment. It is not practical to use this test regularly in CF patients, to prevent further hearing loss. We will evaluate a new hearing test &ndash; the High Frequency Digit Triplet (HFDT) test. This test mimics how individuals hear in real life situations (such as a noisy room), requires only a computer and does not need clinically trained personnel. We will evaluate the new test in stable patients and in those about to receive intravenous antibiotics for a chest infection. We will also see if it is feasible to do the test in primary school children. If the HFDT test is accurate and practical, we will apply for a new research grant which would allow us to see if the test is accurate when performed in the home (where there may be more background noise). We could then offer this test to every CF patient in the UK, over 5 years. Patients could perform the test at home and then bring the result to discuss with their doctor, if antibiotic treatment is likely. We believe this test could prevent hearing loss in many people with CF and allow substantial savings both in testing and in hearing aid provision (where hearing is irreversibly damaged).

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EAR;CONGENITAL DISORDERS