Phenotyping Noise Induced Hearing Loss with Audiometry and

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Phenotyping Noise Induced Hearing Loss with Audiometry and DPOAEs Ishan Bhatt, Ph. D. ,

Phenotyping Noise Induced Hearing Loss with Audiometry and DPOAEs Ishan Bhatt, Ph. D. , NAU Susan L. Phillips, Ph. D. , UNCG Mohsin Ahmed Shaikh, Ph. D. candidate, UNCG 1

Disclosure • Dr. Susan Phillips, Mr. Mohsin Ahmed Shaikh and I have no relevant

Disclosure • Dr. Susan Phillips, Mr. Mohsin Ahmed Shaikh and I have no relevant financial or nonfinancial relationships to disclose. • The material presented today is based on audiometric and otoacoustic emissions (OAEs) data collected from the School of Music, University of North Carolina at Greensboro. The study was approved by the Institutional Review Board, UNCG (11 -0335). 2

Key Factors in Noise-induced Hearing Loss • Globally growing hearing health concern Gene Environment

Key Factors in Noise-induced Hearing Loss • Globally growing hearing health concern Gene Environment • NIHL is a complex disorder • Some individuals are more susceptible than others Gene-environment interaction 3

Importance of Phenotyping NIHL • Success of gene mapping lies on the ability to

Importance of Phenotyping NIHL • Success of gene mapping lies on the ability to define the target phenotype (i. e. trait of a disease) with accuracy and precision (Schulze & Mc. Mahon, 2004) 4

Early Efforts: Phenotyping NIHL • Definition: Absolute audiometric thresholds at high frequencies (3 to

Early Efforts: Phenotyping NIHL • Definition: Absolute audiometric thresholds at high frequencies (3 to 8 k. Hz) • Industrial population • Confounding variables (Sliwinska-Kowalska & Pawelczyk, 2013; Van Laer et al. , 2006) 5

Recent Efforts: Phenotyping NIHL • Definition: Bilateral audiometric notch within 4 to 6 k.

Recent Efforts: Phenotyping NIHL • Definition: Bilateral audiometric notch within 4 to 6 k. Hz Potential NIHL Phenotypes • Collage-aged student musicians • Better control over confounding variables (Phillips et al. , 2012) 6

Purpose of the Study • To evaluate the 4 -6 k. Hz audiometric notch

Purpose of the Study • To evaluate the 4 -6 k. Hz audiometric notch using a test battery of Distortion-Product Otoacoustic Emissions (DPOAEs) • Hypothesis: Musicians with 4 -6 k. Hz audiometric notch will exhibit reduced DPOAEs compared to musicians without the notch 7

Method • Sample ü 77 musicians ü 18 -31 years üNormal otoscopic examination and

Method • Sample ü 77 musicians ü 18 -31 years üNormal otoscopic examination and tympanometric findings • DPOAE measured in the left ear • Online Survey üPrimary instruments üParticipation in ensembles üExposure to music 8

DPOAE Test Battery • DPOAE I/O function (ILO 292 -II V 6): ü 2

DPOAE Test Battery • DPOAE I/O function (ILO 292 -II V 6): ü 2 f 1 - f 2 DP frequency at 2, 3, 4 and 6 k. Hz üL 2 ranging from 75 to 30 d. B SPL in 5 d. B steps üFormula-based approach: L 1 = (0. 4)L 2+39 • 2 f 1 - f 2 DPgram was measured from 2 to 8 k. Hz in 9 data points/octave with L 1 and L 2 were 60 and 40 d. B SPL respectively 9

Statistical Analysis • Repeated measure ANOVA üWithin subject factors: 10 DP data points, üBetween

Statistical Analysis • Repeated measure ANOVA üWithin subject factors: 10 DP data points, üBetween subject factors: Audiometric groups and music exposure üCovariate: Gender 10

Results • 55/77(23 females and 32 males) participants completed survey • 18/55 showed 4

Results • 55/77(23 females and 32 males) participants completed survey • 18/55 showed 4 -6 k. Hz audiometric notch • 5/55 showed high frequency drop 11

Results continue… • DPOAE I/O function: ü Main effect of exposure to music was

Results continue… • DPOAE I/O function: ü Main effect of exposure to music was statistically significant (p= 0. 029) ü Main effect of audiometric groups was not statistically significant (p>0. 05) 1 2 3 4 12

Results continue… • Main effect of music exposure: DPgram ü Frequency range (2 -4

Results continue… • Main effect of music exposure: DPgram ü Frequency range (2 -4 k. Hz): F (3, 44) = 4. 78, p= 0. 006 ü Frequency range (4 -8 k. Hz): F (3, 44) = 2. 884, p= 0. 046 • Main effect of audiometric groups: No statistically significant effect found 1 2 3 4 13

DPOAEs in 3 Audiometric Configurations DPgram: 2 -8 k. Hz (9 data points/octave) 14

DPOAEs in 3 Audiometric Configurations DPgram: 2 -8 k. Hz (9 data points/octave) 14

Discussion • No effect of audiometric configurations on DPOAEs • Observation can be attributed

Discussion • No effect of audiometric configurations on DPOAEs • Observation can be attributed to: ü DPOAE recording limitations and/or ü Physiological basis Standing Waves in the Ear Canal 15

Damage to OHCs Elevated audiometric thresholds and comparatively poor DPOAEs (Bhagat et al. ,

Damage to OHCs Elevated audiometric thresholds and comparatively poor DPOAEs (Bhagat et al. , 2010; Hofstetter, Ding, Powers, & Salvi, 1997; Ozturan, Jerger, Lew, & Lynch, 1996) Damage to Stria Vascularis Elevated audiometric thresholds and comparatively better DPOAEs (Mills, Norton, & Rubel, 1993; Gates et al. , 2002) 16

Conclusion • Musicians with higher music exposure are likely to show reduction in DPOAE

Conclusion • Musicians with higher music exposure are likely to show reduction in DPOAE amplitude • Further research in required to investigate DPOAEs in musicians with the 4 -6 k. Hz audiometric notch 17

Future Research • DPOAE recording using advance calibration technique • A well-defined control group

Future Research • DPOAE recording using advance calibration technique • A well-defined control group of non-musicians may improve sensitivity of the future studies • Animal study to validate potential subphenotypes • Validate the music exposure survey 18

References Bhagat, S. P. , Bass, J. K. , White, S. T. , Qaddoumi,

References Bhagat, S. P. , Bass, J. K. , White, S. T. , Qaddoumi, I. , Wilson, M. W. , Wu, J. , & Rodriguez-Galindo, C. (2010). Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma. International Journal of Pediatric Otorhinolaryngology, 74(10), 1156 -1163. Gates, G. A. , Mills, D. , Nam, B. H. , D'Agostino, R. , & Rubel, E. W. (2002). Effects of age on the distortion product otoacoustic emission growth functions. Hearing Research, 163(1 -2), 53 -60. Hofstetter, P. , Ding, D. , Powers, N. , & Salvi, R. (1997). Quantitative relationship of carboplatin dose to magnitude of inner and outer hair cell loss and the reduction in distortion product otoacoustic emission amplitude in chinchillas. Hearing Research, 112(1 -2), 199 -215. Mills, D. M. , Norton, S. J. , & Rubel, E. W. (1993). Vulnerability and adaptation of distortion product otoacoustic emissions to endocochlear potential variation. Journal of The Acoustical Society of America, 94(4), 2108 -2122. Ozturan, O. , Jerger, J. , Lew, H. , & Lynch, G. R. (1996). Monitoring of cisplatin ototoxicity by distortion-product otoacoustic emissions. Auris Nasus Larynx, 23, 147 -151. Phillips, S. L. , Mace, S. T. , Richter, S. J. , Morehouse, R. , Henrich, V. C. (2012). Genetic Bases of Noise Induced Hearing Loss. Podium presentation at the American Auditory Society conference, Scottsdale, Arizona, March. Schulze, T. G. , Mc. Mahon, F. J. 2004. Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. Hum. Hered. , 58, 131 -138. Sliwinska-Kowalska, M. , & Pawelczyk, M. (2013). Contribution of genetic factors to noise-induced hearing loss: a human studies review. Mutation Research, 752(1), 61 -65. Van Laer, L. , Carlsson, P. , Ottschytsch, N. , Bondeson, M. , Konings, A. , Vandevelde, A. , & Dieltjens, N. (2006). The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss. Human Mutation, 27(8), 786 -795. 19