Development and validation of an efficient music exposure paradigm for use in Temporary Threshold Shift clinical trials.
Creators: name: Iliadou, Eleftheria
Publisher: name: Open Science Framework
Year: 2022
Subjects: subject: Medicine and Health Sciences
subject: Noise-induced hearing loss
subject: Temporary threshold shift

description: Temporary threshold shift (TTS) has long been used as an early audiometric biomarker of traumatic noise exposure and as a valid proxy for noise-induced permanent threshold shift (NIPTS). To date, multiple studies have used music exposure to assess participants’ temporary cochlear dysfunction. Nevertheless, materials and methods used to create and measure TTS vary largely across studies making meta-analysis of results challenging. Previous music exposure paradigms that efficiently caused TTS lasted up to 4 hours, while shorter ones did not manage to create TTS that was detectable reliably by other than pure tone audiometry (PTA) hearing test (i.e., otoacoustic emissions). The main objective of the present study is the creation of an easily reproducible, pleasant and brief music exposure paradigm that safely creates and measures temporary cochlear dysfunction, based on methodological and ethical aspects of previously published experimental paradigms. The study methodology includes the following: - Participants Participants were recruited from the 1st Otorhinolaryngology Department of the National and Kapodistrian University of Athens and underwent medical and hearing loss history, otomicroscopy, tympanometry (GSI TympStar Version 2), and PTA. Those fulfilling inclusion criteria (normal hearing, no hearing disorder history) received oral and written explanations of the study purpose and procedures and were asked to sign the relevant consent form. - Participants’ assessment Included participants underwent: (1) Medical and hearing loss anamnesis. Lifetime noise exposure was evaluated using the noise exposure structured interview (NESI; (Guest et al, 2018). Duration: 10’. Endpoints: age, sex, NESI units. (2) Hearing testing: a. PTA and extended high frequency PTA (EHF-PTA) using Interacoustics Affinity audiometer (EN 60645-1, ANSI S3.6), and TDH39 and HDA 300 headphones (for &gt;8 kHz). Tested frequencies were 1, 3, 6, 8, 10, and 12.5 kHz [with the addition of 4 kHz after the further manipulation of our audio material (see below)]. The signal level was varied in a 6 dB down, 2 dB up manner. Since conductive hearing loss was an exclusion criterion, no air-bone gap was expected. It was thus decided that only air conduction would be measured. Duration: ~5’. Endpoints: PTA thresholds before and after music exposure per frequency b. DPOAEs using Interacoustics Titan. The frequency ratio of primary tones, f1:f2, was 1.22, and their levels were 65 and 55 dB SPL, respectively. Maximum residual noise was set to 30 dB SPL. The geometric mean of the pair was swept from 8 to 1 kHz, with measurements conducted at two points per octave. Data collection was terminated after three such sweeps. Duration: 1’. Endpoints: DPOAE amplitude before and after music exposure per frequency. - Procedure All participants were advised not to expose themselves to further loud noise or music 72h prior and during study procedures. They underwent anamnesis, and baseline PTA and DPOAE testing just before music exposure. Then, according to their preference, they were exposed to the audio material at 100dBA or 97 dBA for 15’ or 30’ respectively. The audio material was provided by means of headphones to the left ear connected to the same laptop, always under the same conditions, in an audiological booth. The contralateral (right) ear was sealed. Caution was taken not to exceed the overall acoustic energy that would result in PTS, according to previous studies’ findings and national and European legislation. Immediately after music exposure, participants were asked to rate their comfort level during the experimentation and the degree of aural fullness, on scales from 1 to 10. 2’ after the end of music, they underwent DPOAE testing. At 3’- 4’ after the end of music, PTA was performed. PTA and DPOAEs were repeated later, within 24h, to ensure that PTA and DPOAEs returned to baseline. - Statistical analysis A three-level linear mixed effect model was used to reflect the multilevel structure of data (repeated measurements of PTA thresholds and DPOAE levels at different frequencies, before and after exposure, within the same participant) of cochlear regions corresponding to tested frequencies nested into participants. Age, Sex, NESI units, and the interaction between Exposure and Frequency were modelled as fixed factors. Random effects were modelled by a random intercept of Frequency within Participant to account for individual differences in thresholds for each frequency for each participant, before exposure. A random slope of Exposure within Participant was also fitted to account for differences in the magnitude of the effect of music exposure for each individual. Statistics were computed using R statistical language. The linear mixed models were created using the lme4 package and fitted by the restricted maximum likelihood method and t-tests using Satterthwaite's method. Model selection was based on backward stepwise regression. Deviations from homoscedasticity or normality was verified by visual inspection of both residual and random effect plots, and the Kolmogorov-Smirnov test. Analysis of variance tables (using the Kenward–Rogers method for estimating degrees of freedom), marginal means and significance testing of their differences (using Tukey’s HSD method to adjust p-values for multiple comparisons) were calculated via the lmerTest package.