Objectives: One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects.
Design: Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later.
Results: Changes in thresholds after the lowest-level exposure were difficult to distinguish from test–retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0–14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure.
Conclusions: These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.
The authors describe real-world digital music exposures that reliably induce small temporary threshold shift in normal hearing human subjects. Effects of digital audio player use on hearing sensitivity were measured in 33 subjects that listened to rock or pop music playlists for four hours at ~94 (n=10), ~99 (n=11), or ~100 (n=12) dB-A in-ear level. Temporary threshold shift was greatest at 4 kHz. The authors describe variability of temporary threshold shift induced by music player use in this healthy, normal-hearing, young adult population, and demonstrate complete recovery. The authors propose the protocol as appropriate for evaluation of interventions of otoprotection potential, with the requirement that subjects be fully informed of potential risks.
1Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, Florida, USA;
2Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA;
3Department of Otolaryngology, University of Florida, Gainesville, Florida, USA;
4Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan, USA;
5Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
ACKNOWLEDGMENTS: The authors thank the members of the Data Safety Monitoring Board selected by the National Institutes of Health, and Gordon Hughes at the National Institutes of Health, for helpful feedback and suggestions throughout their oversight of these studies, and their review of an earlier version of this article. The authors are also grateful to Sharon Kujawa for guidance on the DPOAE protocols and discussion of safety issues, and for her comments and suggestions on an earlier version of this article. The authors also acknowledge the contributions of Jim Wyatt, Marcello Pineiro, and Robert Trahoitis at Brüel and Kjær, who were instrumental in developing calibration protocols. In addition, the authors thank Sebastian de la Calle, Kari Morgenstein, Marissa Rosa, Jason Schmitt, and Lindsey Willis-Banks, who consented and tested subjects at the University of Florida, and Susan DeRemer at the University of Michigan, who provided assistance with institutional review board applications.
The project was supported by U01 DC 008423 from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, awarded to the University of Michigan (J. M. M.), via a subcontract awarded to the University of Florida (C. G. L.)
The authors have no funding or conflicts of interest to disclose.
Address for correspondence: Colleen G. Le Prell, Box 100174, Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL 32610, USA. E-mail: email@example.com
Editor’s Note: The work described in this article was approved by two institutional review boards (The University of Michigan and The University of Florida) and had the added safety benefit of being reviewed by an independent NIH Data Safety and Monitoring committee. Thus, the work met (and in many respects exceeded) standards for research involving humans. Recent evidence from studies in rodents (Kujawa and Liberman 2006, 2009; Lin et al. 2011), however, suggests that experimentally induced TTS may result in permanent, degenerative changes to the auditory nerve even after auditory thresholds and distortion product otoacoustic emissions return to pre-exposure levels. Le Prell and colleagues describe these recent data from rodents, but note that the TTS induced in their study in humans is less than the TTS that caused permanent changes in the rodent auditory nerve. Still, as noted by the authors at several places in this article, care must be taken to fully inform potential subjects in any future TTS studies in humans, including those that involve therapeutic interventions, that they may be at increased risk of neural degeneration even if both audiometric thresholds and DPOAE levels return to pre-exposure values. The Editorial Board of Ear and Hearing reiterates this view in the interests of subject safety and in an effort to assure that subjects in future studies are fully informed of potential risks, however small they may be.
Received June 13, 2011
Accepted May 14, 2012