A MULTICENTRE PROSPECTIVE STUDY OF TABLET

AND WEB-BASED AUDIOMETRY TO DETECT

OTOTOXICITY IN ADULTS WITH CYSTIC FIBROSIS
A. Vijayasingam, E Frost, J Wilkins, P Premachandra, K
Mclaren, L Picinali, A Vidal-Diaz, M Ni, D Morris-Rosendahl, J
Harcourt, C Elston, N Simmonds, A Shah
 Background
• Individuals with Cystic Fibrosis (CF) often receive frequent and prolonged courses
of aminoglycosides which may result in the development of ototoxicity.

• Reported prevalence of ototoxicity ~40% in adults with CF.

• High frequency audiometry is sensitive for early detection
• No current national or international recommendations to screen for ototoxicity.

• Problems with implementation of screening:

• Access to audiology/ENT (often not on site)
• Additional clinic appointments
• Logistics of annual audiology for CF cohorts
• Extended high-frequency audiometry routinely not performed

References: 1. Garinis et al. J. Cystic Fibrosis 2017; 2. Caumo et al. Br J Otorhinolaryngology; 3. Konrad-Martin et al. Int J Audiology 2017
 Study design
Aim:
Analyse the utility of tablet audiometry alongside web-based ototoxicity
test to screen for ototoxicity
• Web based test developed by 3D Tune-In at
Dyson School of Design Engineering, Imperial
College London

• 3 frequencies - 500 Hz, 1000Hz , 4000Hz

• Any environment/device

• Can use any standard headphones

• iPad audiometer developed
by Shoebox Audiometry,
Clearwater Clinical Ltd
• CE Marked
• Validation studies in healthy
adults and children in
Canada
• Sound booth not required
• Performed by non -
audiologists
• Noise cancelling headset
• Six standard frequencies
plus extended high
frequencies (10,000Hz and
12,500Hz)
■ Formal audiometry (FA) in sound booths
at two specialist Audiology departments

■ Calibrated high frequency headphones

■ OTOsuite software

■ Six standard frequencies plus extended

high frequencies( 10,000Hz and
12,500Hz)

■ Validated Hearing, Tinnitus, Vertigo

symptom questionnaires

■ Validated usability questionnaires for

each hearing test
 Overall prevalence of hearing loss
• Any threshold value
> 25dB classed as
abnormal
• Overall prevalence
of abnormal hearing
(across any
frequency)
• 53/110 48%
• Majority of hearing
loss in higher
frequencies
Severity of hearing loss

~8%
Is age the only factor?
 Univariate analysis of risk factors for hearing loss
P-value Univariate
All Normal Abnormal
analysis
Sex (%Male) 58.73 60.87 56.14 0.5916
Pseudomonas (%Yes) 58.56 91.3 94.74 0.4610
Fungal disease treated (%Yes) 38.39 44.93 31.58 0.1276
Mycobacterial disease treated (%Yes) 19.84 21.74 17.54 0.5573
DIOS (%Yes) 27.78 24.64 31.58 0.3875
Pancreatic insufficiency (%Yes) 90.48 92.75 87.72 0.3430
Chronic sinusitis (%Yes) 32.54 27.54 38.60 0.1888
eGFR (%>90) 71.77 79.10 63.16 0.0516
Azithromycin (%Yes) 63.49 55.07 73.68 0.0324
HIAA Score (% Abnormal) 11.11 10.14 12.28 0.7046
Tinnitus Score (% Abnormal) 9.52 8.70 10.53 0.7279
Dizziness Score (% Abnormal) 7.14 8.70 5.26 0.4610
Age (Median (IQR)) 31.5 (24-42) 30 (24-34) 42 (29-49) <0.0001
FEV1 (Median (IQR)) 2.1 (1.54-2.92) 2.56 (1.7-3.07) 1.85 (1.39-2.75) 0.0076
FEV1 %predicted (Median (IQR)) 62 (46-80) 72 (51-82) 61 (46-73) 0.1662

BMI (Median (IQR)) 22 (20.1-23.8) 21.5 (20-22.6) 22.3 (20.4 - 24.6) 0.0687

Total exacerbations (Median (IQR)) 4 (2-10) 4 (2-8) 5 (2-12) 0.0352

Total days of Ivs (Median (IQR)) 56 (21-154) 56 (28-119) 56 (28-182) 0.0257

*IV Tobramycin 28 (6-75) 28 (3-111) 28 (7-66.5) 0.0788
*Inhaled Tobramycin 224 (0-2240) 56 (0-1344) 938 (0-3001) 0.0748
 Multivariate analysis

• Age and Total exacerbations in the last 10 years were significant

• For each year older, the probability of having an abnormal hearing

test increases 13.9% (95% CI: 8% - 20.1%;p-value: <0.0001)

• For each extra exacerbation, the probability of having an abnormal

result increases 10% (95% CI: 3% - 17.6%;p-value: 0.0047).
Effect of IV use on ototoxicity
Utility of screening tests to identify ototoxicity in adults with CF

HIAA
Ipad WB
Questionnaire

Apparent prevalence 0.48 (0.39, 0.57) 0.07 (0.03, 0.12) 0.11 (0.06, 0.18)

True prevalence 0.45 (0.39, 0.54) 0.46 (0.37, 0.55) 0.45 (0.36, 0.54)

Sensitivity 0.93 (0.83, 0.98) 0.14 (0.06, 0.26) 0.12 (0.05, 0.24)

Specificity 0.88 (0.78, 0.95) 1.00 (0.95, 1.00) 0.90 (0.80, 0.96)

Positive predictive value 0.87 (0.76, 0.94) 1.00 (0.63, 1.00) 0.50 (0.23, 0.77)

Negative predictive value 0.94 (0.85, 0.98) 0.58 (0.49, 0.67) 0.55 (0.45, 0.65)
Intra-class correlation coefficient between iPad and formal audiometry

Test ICC 95% CI

250 Hz Left 0.838 .712 .901

250 Hz Right 0.821 .745 .874

500 Hz Left 0.868 .812 .907
500 Hz Right 0.669 .531 .767
1000 Hz Left 0.871 .817 .910
1000 Hz Right 0.946 .923 .962
2000 Hz Left 0.837 0.768 0.885
2000 Hz Right 0.940 0.915 0.958

4000 Hz Left 0.936 0.909 0.955

4000 Hz Right 0.901 0.859 0.930

8000 Hz Left 0.927 0.892 0.950

8000 Hz Right 0.952 0.931 0.966

10000 Hz Left 0.962 0.947 0.974
10000 Hz Right 0.960 0.943 0.972
12500 Hz Left 0.957 0.939 0.970
12500 Hz Right 0.976 0.966 0.983
 Usability analysis of hearing devices
Scales Audiometry Web-based iPad
UMUX and grade 77.5 (B+) 72(C+) 78 (B+)
NPS +62 +11 +68
UEQ Fig. a Fig. b Fig. c (shown below)
Attractiveness Above Average (1.36) Below average (0.92) Above Average (1.39)
Perspicuity Excellent (2.49) Excellent (1.92) Excellent (2.32)
Efficiency Excellent (1.85) Above Average (1.23) Good (1.69)
Dependability Above Average (1.38) Below average (0.82) Below average (0.93)
Stimulation Below Average (0.93) Below average (0.68) Above Average (1.00)
Novelty Bad (0.02) Below average (0.57) Above Average (0.80)

Figurative illustration of usability of Ipad hearing test

 Summary
■ There is a high prevalence of ototoxicity in adults with CF

■ Age and IV antibiotic usage is associated with hearing loss in

adults with CF

■ Ipad-based audiometry (Shoebox MD) is highly sensitive,

specific and reliable to screen for ototoxicity in an adult CF
population
 Age cut-off for screening..

%
Age % abnormal >=
Se < cutoff Sp < cutoff Se >= cutoff Sp >= cutoff abnormal <
cutoff cutoff
cutoff

0.88 0.92 0.97 0.67

40 28.6% 78.6%
(0.68-0.97) (0.82-0.97) (0.84-1) (0.30-0.93)

0.89 0.91 0.97 0.67

41 29.2% 83.8%
(0.70-0.98) (0.80-0.96) (0.83-1) (0.22-0.96)

0.91
0.89 0.97 0.6
42 29.7% 85.7%
(0.71-0.98) (0.83-1 (0.15-0.95)
(0.81-0.97)

0.87 0.91 1 0.5

43 32.3% 86.7%
(0.70-0.96) (0.81-0.97) (0.87-1) (0.07-0.93)

0.88 0.90 1 0.5

44 33.0% 92.3%
(0.72-0.97) (0.80-0.96) (0.86-1) (0.01-0.99)

0.89 0.90 1 0.5

45 34.3% 91.7%
(0.73-0.97) (0.80-0.96) (0.85-1) (0.01-0.99)
 HIAA questionnaire +
Tablet-based audiometry

Abnormal audiometry Normal audiometry

Formal sound-booth Normal Repeat screening questionnaire and tablet

audiometry audiometry in 12 months

Abnormal

Yes No ototoxic Stable

Audiology/ENT Indication for urgent
referral via GP audiology/ENT referral medication
Refer for formal
No Repeat tablet audiometry in 3-6 months. audiology if >15db
change in threshold or
new abnormality
Evidence of mixed conductive-
sensorineural hearing loss

Yes Ongoing
Azithromycin
* Formal sound-booth No
audiometry f/u
Increased frequency tablet audiometry
during administration (at discretion of
clinician)
Tablet audiometry to monitor change
Discuss with patient regarding future use of Ongoing IV
ototoxic medication ototoxic medication

*Repeat formal audiometry at similar timescales to tablet audiometry and discuss future ototoxic medication use
 Acknowledgements
CF teams: Imperial College:
- Dr Anitha Vijayasingam - Dr Alberto Vidal-Diaz
- Dr Kate Mclaren - Dr Melody Zhifang Ni
- Dr Nicholas Simmonds - Dr Lorenzo Picinali
- Dr Caroline Elston
Clinical genetics:
- Dr Deborah Morris-Rosendahl
Audiology/ENT:
- Julie Wilkins Funding:
- Emily Frost - CF Trust
- Presanna Premachandra - NHS Darzi fellowship

- Mr Jonny Harcourt