Dataset Information

Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for Serial Monitoring of Cochlear Function in Adults.

ABSTRACT: Distortion product otoacoustic emissions (DPOAEs) have long been heralded as a means to objectively monitor cochlear function and increasingly are becoming a key component in hearing surveillance programs for individuals at risk for ototoxic- and occupational noise-related hearing loss. Yet clinicians are unsure how to define clinically meaningful shifts in DPOAE level. In this study, a meta-analysis approach is used to synthesize the DPOAE level test-retest literature to construct a set of DPOAE level shift reference limits that can be used clinically to define a statistically significant emission change.The authors reviewed all published articles identified through a Medline search using the terms "Otoacoustic Emission Variability," "Otoacoustic Emission Reliability," "Otoacoustic Emission Repeatability," and "Otoacoustic Emission Test Retest" restricted to DPOAEs, adults, and English language. Articles with DPOAE level data elicited by moderate stimulus levels for f2 frequencies of 1000, 2000, 4000, or 6000 Hz were selected because these stimulus parameters were relatively well represented in the literature. The authors only included articles that reported the standard error of the measurement (SEM) or from which the SEM could be calculated. Meta-analysis was used to estimate the population mean SEM over the included studies. Models were fit separately for each f2 primary and included days since baseline and study-specific random effects.Ten DPOAE test-retest studies met inclusion criteria for this meta-analysis. The SEM values varied widely across published studies (0.57 to 3.9 dB) and were provided for relatively short time intervals (less than 15 days on average). Time, or days since baseline, was statistically significant at higher f2 frequencies (4000 and 6000 Hz). From the model results, 90% reference limits specific to the f2 and elapsed time between baseline and follow-up measurements were established. Reference limits provided correspond to negative (emission decrement) and positive (emission enhancement) shifts indicative of the amount of measurement variability that, using this approach, must be tolerated as "normal" fluctuations over time. Changes larger than the reference limits are considered significant and warrant follow-up testing.The meta-analysis presented provides reference limits that are appropriate for a set of specific f2 frequencies and time intervals. The meta-analysis concerns the SEM statistic directly, so that any preferred reference limit can be computed from the results and should be predicated upon the screening application. The presumed advantage of this meta-analytic approach is increased precision relative to limits suggested by any of the individual studies included in the analysis.

SUBMITTER: Reavis KM

PROVIDER: S-EPMC4632966 | biostudies-literature | 2015 Sep-Oct

REPOSITORIES: biostudies-literature

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Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for Serial Monitoring of Cochlear Function in Adults.

Reavis Kelly M KM McMillan Garnett P GP Dille Marilyn F MF Konrad-Martin Dawn D

Ear and hearing 20150901 5

<h4>Objective</h4>Distortion product otoacoustic emissions (DPOAEs) have long been heralded as a means to objectively monitor cochlear function and increasingly are becoming a key component in hearing surveillance programs for individuals at risk for ototoxic- and occupational noise-related hearing loss. Yet clinicians are unsure how to define clinically meaningful shifts in DPOAE level. In this study, a meta-analysis approach is used to synthesize the DPOAE level test-retest literature to const ...[more]

PMID: 25985018

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Project description:OBJECTIVE:Distortion-product otoacoustic emissions (DPOAEs) provide a rapid, noninvasive measure of outer hair cell damage associated with chemotherapy and are a key component of pediatric ototoxicity monitoring. Serial monitoring of DPOAE levels in reference to baseline measures is one method for detecting ototoxic damage. Interpreting DPOAE findings in this context requires that test-retest differences be considered in relation to normal variability, data which are lacking in children. This study sought to (1) characterize normal test-retest variability in DPOAE level over the long time periods reflective of pediatric chemotherapy regimens for a variety of childhood ages and f2 primary frequencies using common clinical instrumentation and stimulus parameters; (2) develop level-shift reference intervals; and (3) account for any age-related change in DPOAE level or measurement error that may occur as the auditory system undergoes maturational change early in life. DESIGN:Serial DPOAE measurements were obtained in 38 healthy children (25 females and 13 males) with normal hearing and ranging in age from one month to 10 years at the initial (baseline) visit. On average, children were tested 5.2 times over an observation period of 6.5 months. Data were collected in the form of DP grams, in which DPOAE level was measured for f2 ranging from 1.4 to 10 kHz, using a fixed f2/f1 ratio of 1.22 and stimulus level of 65/55 dB SPL for L1/L2. Age effects on DPOAE level and measurement error were estimated using Bayesian regression of the longitudinal data. The raw and model-based distribution of DPOAE test-retest differences were characterized using means and standard error of the measurement for several ages and f2's. RESULTS:DPOAE test-retest differences for the children in this study are at the high end of those previously observed in adults, as reflected in the associated shift reference intervals. Further, although we observe substantial child-specific variation in DPOAE level, the pattern of age-related changes is highly consistent across children. Across a wide range of f2's, DPOAE level decreases by 3 to 4 dB from 1 to 13 months of age followed by a more gradual decline of <1 dB/year. An f2 of 6 kHz shows the smallest decrease during the early rapid maturation period. DPOAE measurement error is fairly constant with age. It is 3 to 4 dB at most f2's and is greater (indicating poorer reliability) at 1.5, 8, and 10 kHz. CONCLUSIONS:DPOAE level decreases with childhood age, with the greatest changes observed in the first year of life. Maturational effects during infancy and greater measurement error at very low and high f2's affect test-retest variability in children. An f2 of 6 kHz shows minimal maturation and measurement error, suggesting it may be an optimal sentinel frequency for ototoxicity monitoring in pediatric patients. Once validated with locally developed normative data, reference intervals provided herein could be used to determine screen fail criteria for serial monitoring using DPOAEs. Employing state-of-the-art calibration techniques might reduce variability, allowing for more sensitive screen fail criteria.

Project description:BackgroundAlthough several candidate-gene association studies have been conducted to investigate noise-induced hearing loss (NIHL) in humans, most are underpowered, unreplicated, and account for only a fraction of the genetic risk. Mouse genome-wide association studies (GWASs) have revolutionized the field of genetics and have led to the discovery of hundreds of genes involved in complex traits. The hybrid mouse diversity panel (HMDP) is a collection of classic inbred and recombinant inbred strains whose genomes have been either genotyped at high resolution or sequenced. To further investigate the genetics of NIHL, we report the first GWAS based on distortion product otoacoustic emission (DPOAE) measurements and the HMDP.MethodsA total of 102 strains (n = 635) from the HMDP were evaluated based on DPOAE suprathreshold amplitudes before and after noise exposure. DPOAE amplitude variation was set at 60 and 70 dB SPL of the primary tones for each frequency separately (8, 11.3, 16, 22.6, and 32 kHz). These values provided an indirect assessment of outer hair cell integrity. Six-week-old mice were exposed for 2 h to 10 kHz octave-band noise at 108 dB SPL. To perform local expression quantitative trait locus (eQTL) analysis, gene expression microarray profiles were generated using cochlear RNA from 64 hybrid mouse strains (n = 3 arrays per strain).ResultsSeveral new loci were identified and positional candidate-genes associated with NIHL were prioritized, especially after noise exposure (1 locus at baseline and 5 loci after exposure). A total of 35 candidate genes in these 6 loci were identified with at least 1 probe whose expression was regulated by a significant cis-eQTL in the cochlea. After careful analysis of the candidate genes based on cochlear gene expression, 2 candidate genes were prioritized: Eya1 (baseline) and Efr3a (post-exposure).Discussion and conclusionFor the first time, an association analysis with correction for population structure was used to map several loci for hearing traits in inbred strains of mice based on DPOAE suprathreshold amplitudes before and after noise exposure. Our results identified a number of novel loci and candidate genes for susceptibility to NIHL, especially the Eya1 and Efr3a genes. Our findings validate the power of the HMDP for detecting NIHL susceptibility genes.

Dataset Information

Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for Serial Monitoring of Cochlear Function in Adults.

Publications

Meta-Analysis of Distortion Product Otoacoustic Emission Retest Variability for Serial Monitoring of Cochlear Function in Adults.

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