Jane S. Gordon

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 f2s from 0.8 to 8.0 kHz in 1/6-octave increments using primary levels (L1/L2) of 65/59 dB SPL and a primary frequency ratio (f2/f1) 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 ears with poorer pre-exposure hearing, and in ears with measurable DPOAE frequencies limited to f2s 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 f2s 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 subjects 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 f2s. Results suggest that successful monitoring of ototoxicity with DPOAEs may be predicted clinically by assessing the measurable DPOAE f2 frequency range and its relation to the highest behavioral test frequencies.

Evaluation of insert earphones for high-frequency bedside ototoxicity monitoring

Ototoxic hearing loss is usually detected earliest through monitoring of the highest audible frequencies in individuals administered ototoxic medications. Conducting ototoxicity monitoring may require testing patients in the hospital room. This study evaluated the use of insert earphones for obtaining reliable threshold responses at bedside. Twenty adult subjects were tested during two different sessions in the sound booth and on the ward. Thresholds were obtained for frequencies from 5 to 16 kHz and at 2 kHz with the use of the KOSS Pro/4X Plus earphones and Etymotic ER-4B MicroPro insert earphones. Results indicate that ER-4B insert earphones are as reliable as KOSS earphones for testing on the ward for high-frequency ototoxicity monitoring.

Diabetes-Associated Changes in Cortical Auditory-Evoked Potentials in Relation to Normal Aging.

Objectives: (1) To characterize the influence of type 2 diabetes mellitus (DM) on cortical auditory-evoked potentials (CAEPs) separate from the effects of normal aging, and (2) to determine whether the disease-related effects are modified by insulin dependence. Design: A cross-sectional study was conducted in a large cohort of Veterans to investigate the relationships among type 2 DM, age, and CAEPs in randomly selected participants with (N = 108) and without (N = 114) the disease and who had no more than a moderate hearing loss. Participants with DM were classified as insulin-dependent (IDDM, N = 47) or noninsulin-dependent (NIDDM, N = 61). Other DM measures included concurrent serum glucose, HbA1c, and duration of disease. CAEPs were evoked using a passive homogeneous paradigm (single repeating stimulus) by suprathreshold tones presented to the right ear, left ear, or both ears. Outcome measures were adjusted for the pure-tone threshold average for frequencies of 0.5, 1, and 2 kHz and analyzed for differences in age effects between participant groups using multiple regression. Results: There is little variation across test ear conditions (left, right, binaural) on any CAEP peak in any of the groups. Among no-DM controls, P2 latency increases about 9 msec per decade of life. DM is associated with an additional delay in the P2 latency of 7 and 9 msec for the IDDM and NIDDM groups, respectively. Moreover, the slope of the function relating P2 latency with age is similar across participant groups and thus the DM effect appears constant across age. Effects on N1 latency are considerably weaker, with age effects of less than 4 msec per decade across all groups, and DM effects of only 2 (IDDM) or 3 msec (NIDDM). In the NIDDM group, the slope relating N1 latency to age is steeper relative to that observed for the no-DM group, providing some evidence of accelerated “aging” for this CAEP peak. DM does not substantially reduce N1–P2 amplitude and age relationships with N1–P2 amplitude are effectively absent. There is no association between pure-tone average at 0.5, 1, and 2 kHz and any aspect of CAEPs in this cohort. Conclusions: In a large cohort of Veterans, we found that type 2 DM is associated with prolonged N1 and P2 latencies regardless of whether insulin is required to manage the disease and independent of peripheral hearing thresholds. The DM-related effects on CAEP latencies are threefold greater for P2 compared with N1, and there is little support that at the cortical level, IDDM participants had poorer responses compared with NIDDM participants, although their responses were more variable. Overall, these results indicate that DM is associated with slowed preattentive neural conduction. Moreover, the observed 7 to 9 msec P2 latency delay due to DM is substantial compared with normal age changes in P2, which are 9 msec per decade of life in this cohort. Results also suggest that whereas N1 latency changes with age are more pronounced among individuals with DM versus without DM, there was no evidence for more rapid aging of P2 among patients with DM. Thus, the damage responsible for the major DM-related differences may occur early in the DM disease process. These cross-sectional results should be verified using a longitudinal study design.

Mobile software Apps support personalized-SRO and serial monitoring with results indicating early detection of hearing loss

This paper presents an overview of key software applications implemented for our mobile, full-frequency-range, auditory testing system which is designed to detect changes in hearing sensitivity due to treatment with ototoxic medications. The system can be used efficiently in remote locations such as hospital wards, out-patient clinics, and industrial settings, as well as in patient homes to monitor for hearing change and also to perform general audiometric hearing threshold testing at frequencies out to 20kHz. We believe the system is the worlds first instrument specifically designed to support the Sensitive Range for Ototoxicity (SRO), a shortened serial hearing monitoring protocol which has been shown sensitive and reliable in detecting early hearing change. The primary focus of this paper is to present a functional overview of the main mobile software application designed to support the SRO hearing monitoring protocol. Serial monitoring information for an actual patient is used to illustrate how the main software application is used to monitor and detect hearing change. Analysis of the patients SRO monitoring data demonstrates the systems efficacy in detecting hearing threshold change. Overviews of two other support applications, one used for system calibration in the acoustics laboratory, and one used for acoustic performance verification in the field are also included.