Factors Affecting Sensitivity of Distortion-Product Otoacoustic Emissions to Ototoxic Hearing Loss

Objectives: (1) To determine the ototoxicity detection rate (sensitivity) for distortion-product otoacoustic emissions (DPOAEs) testing in adults who received ototoxic medications and experienced pure-tone threshold changes during the course of treatment; (2) to determine the extent to which DPOAE sensitivity to ototoxicity depends on the type of drug administered (platinum or antibiotic), magnitude of ototoxic threshold shifts, pre-exposure pure-tone threshold, and DPOAE data; and (3) to build a model to predict DPOAE sensitivity. Design: DPOAE and audiometric data were obtained as part of a prospective Veterans Affairs study investigating methods of ototoxicity monitoring. Data were analyzed from 90 ears of 53 subjects receiving ototoxic medications and showing significant hearing changes in at least one ear. Pure-tone threshold data were obtained at frequencies from 0.5 to 20 kHz, using 1/6-octave precision near the upper frequency limit of hearing. DPOAE data are reported for f(2)'s from 0.8 to 8.0 kHz in 1/6-octave increments using primary levels (L-1/L-2) of 65/59 dB SPL and a primary frequency ratio (f(2)/f(1)) of 1.2. Test results were evaluated at various times during drug treatment to determine whether DPOAE level changes were associated with behavioral hearing changes. Univariate and multivariate analysis techniques were used to determine factors that affected DPOAE sensitivity to ototoxic damage. Results: Of the 90 ears examined, 82 (91%) had DPOAEs that could be monitored for changes. Sixty-four of these 82 ears (78%) had DPOAEs that were reduced or absent following drug treatment. DPOAE sensitivity to ototoxicity was unrelated to the type of ototoxic drug administered. Rather, DPOAE sensitivity depended on the magnitude of postexposure hearing changes and on variables related to pre-exposure audiogram and DPOAE measurements. Behavioral hearing changes not detected by DPOAEs were small on average (<7 dB). DPOAE sensitivity was reduced in cars with poorer pre-exposure hearing, and in ears with measurable DPOAE frequencies limited to f(2)'s below 2.5 kHz or more than one octave from the frequency region where hearing change occurred. Results of logistic regression modeling showed that DPOAEs present at f(2)'s greater than 2.5 kHz were associated with the eventual success of ototoxicity monitoring with DPOAEs. However, independent variables examined could not explain differences in the relative timing of behavioral and DPOAE changes. A roughly equivalent proportion of ears experienced DPOAE changes before, during, or after behavioral hearing changes. Conclusions: DPOAEs are a useful screening tool for ototoxicity in adults with pre-exposure hearing loss, but are less sensitive compared with a behavioral test method that targets thresholds near the upper limit of a subject's audible frequency range. Ears successfully monitored for ototoxicity with DPOAEs are those with better pre-exposure hearing, greater postexposure hearing changes, and baseline DPOAEs near the highest behavioral test frequencies and present at high f(2)'s. Results suggest that successful monitoring of ototoxicity with DPOAEs may be predicted clinically by assessing the measurable DPOAE f(2) frequency range and its relation to the highest behavioral test frequencies.