Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. <zdoi; 10.1097/AUD.0000000000000465> 0196/0202/17/XXXX-0000/0 • Ear & Hearing • Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved • Printed in the U.S.A. 1 Objectives: Distortion-product otoacoustic emissions (DPOAEs) are repeatable over time at lower frequencies (≤8 kHz) and higher frequen- cies (>8 kHz) in healthy, normal-hearing subjects. The purpose of this study was to examine the repeatability of DPOAEs measured with high- frequency (HF) stimuli in a patient population. It was hypothesized that HF DPOAEs would be repeatable over four trials. Design: DPOAEs were measured in 40 cystic fibrosis (CF) patients (17 females and 23 males) with measurable behavioral thresholds and pres- ent DPOAEs for at least 2 of the high frequencies tested (8 to 16 kHz). A depth-compensated simulator sound pressure level (SPL) method of calibration was utilized. Each patient attended four trials, in which a complete set of data were collected. At each trial, three different DPOAE paradigms were completed. First, a discrete frequency sweep was mea- sured between 8 and 16 kHz with a ratio (f 2 /f 1 ) of 1.2 and levels of 65/50 dB SPL for L 1 /L 2 . Next, ratio and level sweeps were obtained at the two highest frequencies with a present DPOAE determined from the discrete frequency sweep, and the results were used to calculate DPOAE group delay and DPOAE detection thresholds, respectively. Ratio sweeps were collected with f 2 /f 1 varied from 1.1 to 1.3 and stimulus levels of 60/45 dB SPL (L 1 /L 2 ). Level sweeps were collected with an f 2 /f 1 of 1.22 and L 2 = 50 and L 1 varied between 20 and 70 dB SPL. Differences and correlations between trials, SE of the measurement, and confidence intervals were calculated, as well as a repeated-measures analysis of variance. Results: DPOAE response and behavioral threshold variability in CF patients were not significantly different across four trials. It can be expected in 95% of CF patients that differences between trials of DPOAE levels, group delay, and detection thresholds and behavioral thresholds are less than 6.26 dB, 0.87 msec, 9.34 dB, and 9.60 dB, respectively. Conclusions: 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. Key words: Cystic fibrosis, Detection thresholds, Distortion-product oto- acoustic emissions, Group delay, High-frequency stimuli, Monitoring, Ototoxicity, Repeatability. (Ear & Hearing 2017;XX;00–00) INTRODUCTION When two continuous acoustic pure tones, close in fre- quency (f 1 and f 2 ), are simultaneously presented to the cochlea, acoustic distortion products at frequencies not present in the stimuli are produced due to the nonlinear properties of the basi- lar membrane and can be measured in the ear canal, namely, dis- tortion-product otoacoustic emissions (DPOAEs; Kemp 1978). The frequencies of DPOAEs are arithmetic combinations of the lower (f 1 ) and higher frequency (f 2 ) stimulus tones, and the most prominent and widely studied DPOAE in humans occurs at the frequency of 2f 1 −f 2 . DPOAE generation involves the active motile responses of outer hair cells (OHCs), which are respon- sible for basilar membrane–tuning properties (Ruggero & Rich 1991) and the sensitivity and frequency selectivity observed in the tips of neural tuning curves (Liberman & Dodds 1984). The reduction in level or elimination of emissions in a particular frequency range has been shown to occur with OHC damage in that cochlear region (Brown et al. 1989). DPOAEs can be elicited by varying the frequencies (f 1 and f 2 ), frequency ratio (f 2 /f 1 ), or levels (L 1 and L 2 ) of the evoking stimuli, or primary tones. Traditionally, discrete frequency sweeps, where the frequencies of the primary tones are varied with a fxed ratio and levels, are measured in clinical settings. However, the ratio and levels of the primary tones also can be altered at various frequency regions. When the ratio of the primary tones is varied over a small-frequency region and the stimulus levels are fxed, a group delay value can be calculated from the resultant DPOAE phase. Group delay is related to the travel time along the basilar membrane, and it is expected that higher frequency primary tones will yield shorter group delay values than lower-frequency primary tones, due to the tonotopic nature of the basilar membrane. If the levels of the primary tones are varied, DPOAE growth can be examined, and a detec- tion threshold can be determined. The primary tone levels can vary together equally (L 1 = L 2 ), at a fxed difference (e.g., L 1 = L 2 − 10 dB), or one level can be fxed while the other level is varied (Gaskill & Brown 1990; Stover et al. 1996). Threshold can be defned as the lowest level of the primary tones that evoke an emission that meets specifed criterion values. Regardless of which stimulus parameters are varied to elicit a DPOAE, the result provides an objective measure of cochlear status without requiring a patient response, thus allowing for effciency, elimination of tester or response bias, and bedside administration in unhealthy patients (Ress et al. 1999). Common clinical uses for DPOAEs include hearing screenings, differen- tial diagnosis, and serial monitoring of cochlear damage due to ototoxic agents (noise or medications). Because many damag- ing agents initially target OHCs, monitoring DPOAEs appear ideal for assessing ototoxicity (Roland 2004; Reavis et al. 2008, 2011; Dille et al. 2010). Because a physiological change may be detected before a perceptual difference is noticed by the patient, monitoring DPOAEs may allow for earlier detection of cochlear damage (Katbamna et al. 1999a,b; Ress et al. 1999). Patients who require audiologic monitoring are usually exposed to ototoxic agents for a prolonged period of time, and monitoring should be carried out routinely throughout the duration of exposure (American Speech-Language-Hearing Association 1994; American Academy of Audiology 2009). An effective monitoring tool, therefore, must be reliable across test sessions over short and long periods of time, to ensure that a High-Frequency Distortion-Product Otoacoustic Emission Repeatability in a Patient Population Laura Dreisbach 1 , Erika Zettner 2 , Margaret Chang Liu 1 , Caitlin Meuel Fernhoff 1 , Imola MacPhee 1 , and Arthur Boothroyd 1,2 1 School of Speech, Language, and Hearing Sciences, San Diego State University, San Diego, California, USA; and 2 School of Medicine, University of California, San Diego, California, USA.