Distortion-product otoacoustic emissions (DPOAEs) elicited with stimulus frequencies less than or equal to 8 kHz have been used in hearing clinics to assess whether the middle ear and cochlea are normal, but high-frequency hearing (>4 kHz) is most vulnerable to cochlear pathology. It might prove useful to measure DPOAEs with even higher frequency stimuli (>8 kHz), but there have been few reports of such studies in humans. DPOAEs have been measured in other mammals to the upper range of hearing sensitivity. The purpose of this study was to compare some characteristics of DPOAEs in human subjects elicited with high-frequency stimuli with those that have been extensively measured with lower-frequency stimuli. The primary goal was to establish if the same phenomenon responsible for the behavior of low-frequency DPOAEs is responsible for the behavior of high-frequency DPOAEs. Specifically, the DPOAE level with stimuli varied from 2 to 20 kHz, growth functions of DPOAEs, effects of varying the primary frequency ratio (f2/f1) on the DPOAE level, and DPOAE group delay were determined. Because the behaviors appeared to vary smoothly with stimulus frequency, the study suggests that emissions measured from 2 to 20 kHz were the product of the same biological process.

Antioxidants have been reported to be effective in reducing acoustic trauma in animal models but have not been studied in humans. In this study, the antioxidant N-acetylcysteine (NAC) was evaluated to determine if it would reduce temporary changes in auditory function as a result of exposure to loud music in humans. Pure-tone thresholds and distortion product otoacoustic emissions (DPOAEs) were collected in 31 normal-hearing participants, using a randomized, double-blind, placebo-controlled design, before and after two hours of live music in a nightclub. Using repeated measures analysis of variance, no statistically significant differences were found between participants who received NAC versus a placebo for any of the outcome measures. Across all subjects, the largest pure-tone threshold shift occurred at 4 kHz. DPOAE measures were characterized by reductions in amplitude and a trend for shorter group delay values. When the 3 and 4 kHz data were examined by imposing specific criteria of greater than 2 dB DPOAE amplitude reductions and 10 dB or greater pure-tone threshold shifts, DPOAE reductions occurred more often at 3 kHz, and pure-tone shifts occurred more often at 4 kHz.

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Even though the DPOAE level data obtained at frequencies greater than 8 kHz were more variable than at low frequencies, the higher frequencies were found to be repeatable for both paradigms tested. These results encourage the exploration of high-frequency DPOAE measures to be used as an objective test for monitoring ototoxicity in humans. Testing subjects receiving ototoxic therapies is a necessary step in determining if monitoring high-frequency DPOAEs will successfully predict ototoxic effects.

Gender-based norms for auditory-evoked potentials measures are standard in clinical settings. The results of the present study, in agreement with previous studies, indicate that significant interactions exist between gender and DPOAE group delay values in the lower frequencies, and between gender and DPOAE levels at the higher frequencies. To reach the goal of using high frequency DPOAEs in clinical protocols, such as for auditory neuropathy/dys-synchrony diagnosis and ototoxicity monitoring, DPOAEs elicited with conventional and higher frequency stimuli must be understood, including the role of gender to determine if an effect on clinical protocols would exist.

The purpose of this report is to provide guidance on the use of otoacoustic emissions (OAEs) as a clinical trial outcome measure for pharmaceutical interventions developed to prevent acquired hearing loss secondary to cochlear insult. OAEs are a rapid, noninvasive measure that can be used to monitor cochlear outer hair cell function. Serial monitoring of OAEs is most clearly established for use in hearing conservation and ototoxicity monitoring programs in which they exhibit more frequent and earlier changes compared with pure-tone audiometry. They also show promise in recent human trials of otoprotectants. Questions remain, however, concerning the most appropriate OAE protocols to use and what constitutes a "significant" OAE response change. Measurement system capabilities are expanding and test efficacy will vary across locations and patient populations. Yet, standardizing minimal measurement criteria and reporting of results is needed including documentation of test-retest variability so that useful comparisons can be made across trials. It is also clear that protocols must be theoretically sound based on known patterns of damage, generate valid results in most individuals tested, be accurate, repeatable, and involve minimal time. Based on the potential value added, OAEs should be included in clinical trials when measurement conditions and time permit.

HF DPOAEs were repeatable across four test trials for all three paradigms measured in a group of CF patients. These results are encouraging for the measurement of HF DPOAEs to be monitored in those exposed to ototoxic agents.

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