Date

April 2009

Document Type

Thesis

Degree Name

M.P.H.

Department

Dept. of Public Health and Preventive Medicine

Institution

Oregon Health & Science University

Abstract

Millions of patients in the US risk experiencing loss in hearing sensitivity from ototoxic medications annually. The impact on older individuals with preexisting hearing impairment may be even greater since additional loss can immediately affect their communication ability. The current gold-standard for monitoring ototoxicity is through repeated measurements of high-frequency pure-tone thresholds. However, patients differ in their ability to respond to behavioral testing, they can be categorized as fully responsive, partially responsive, or fully unresponsive. Different monitoring strategies are required to detect incipient ototoxicity in each of these groups. Distortion-product otoacoustic emissions (DPOAE) have been proposed as one such strategy for monitoring patients who are partially responsive or fully unresponsive. The objective of this study is to determine how well DPOAEs identify audiometric pure-tone threshold shifts resulting from ototoxic medication administration. DPOAEs depend on the physiological status of the outer hair cells which are typically affected first by most ototoxic medications and therefore should be a sensitive and specific measure of hearing change. However, there are no accepted protocols for ototoxicity monitoring using DPOAE, particularly for individuals with preexisting hearing loss. Most investigations into DPOAE applications for detecting ototoxicity have used either statistical tests of difference, or test-retest variability estimates derived from control populations. Though useful, these investigations do not provide overall sensitivity and specificity of DPOAE measures. A prospective, observational study design was undertaken to determine the test accuracy of DPOAEs compared to repeated measures of high-frequency pure-tone thresholds. DPOAE test performance (sensitivity and specificity) was evaluated through the construction of receiver operating characteristic curves for different metrics derived from DPOAE input/output functions. DPOAE metrics including the sum of input stimulus levels, sum of output emission amplitudes and sum of signal-to-noise ratios were modeled alone and in combination to discriminate patients with and without hearing loss. The result was a discriminate function which included measures of pre-exposure hearing, drug dose and DPOAEs that accurately predicted ASHA significant hearing change in patients exposed to cisplatin. Once the test characteristics of DPOAE are determined, objective ototoxicity monitoring strategies can be developed. DPOAE are quick and unaffected by patient responsiveness. This model of ototoxicity has the potential to increase the number of patients monitored and thus limit the incidence of ototoxicity and its associated side-effects.

Identifier

doi:10.6083/M4KH0K9B

School

School of Medicine

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