Dawn Konrad-Martin

Diabetes-related changes in hearing†

Determine the effects on hearing of diabetes mellitus (DM) severity.

Age-related changes in the auditory brainstem response

PURPOSEnThis cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. RESEARCH DESIGN AND ANALYSIS: ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, III, and V, and the I-V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds <40 dB HL at 2 kHz and 70 dB HL at 4 kHz in at least one ear. Additionally, the median 2, 3, and 4 kHz pure tone threshold average (PTA2,3,4) for the sample, ∼17 dB HL, was used to delineate subgroups of better and worse hearing ears, and only the better hearing sample was modeled statistically. We modeled ABR responses using age, repetition rate, and PTA2,3,4 as covariates. Random effects were used to model correlation between the two ears of a subject and across repetition rates. Inferences regarding effects of aging on ABR measures at each rate were derived from the fitted model. Results were compared to data from subjects with poorer hearing.nnnRESULTSnAging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I-V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged.nnnCONCLUSIONSnIn a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves I and III. Aging did not influence the I-V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, of central ABR generators.

Distortion-product otoacoustic emission test performance for ototoxicity monitoring

Introduction: A nonbehavioral method for monitoring ototoxicity in patients treated with cisplatin is needed because patients enduring chemotherapy may not be well or cooperative enough to undergo repeated hearing tests. Distortion-product otoacoustic emissions (DPOAEs) provide a nonbehavioral measure of auditory function that is sensitive to cisplatin exposure. However, interpreting DPOAE findings in the context of ototoxicity monitoring requires that their accuracy be determined in relation to a clinically accepted gold standard test. Objectives: Among patients receiving cisplatin for the treatment of cancer, we sought to (1) identify the combination of DPOAE metrics and ototoxicity risk factors that best classified ears with and without ototoxic-induced hearing changes; and (2) evaluate the test performance achieved by the composite measure as well as by DPOAEs alone. Design: Odds of experiencing hearing changes at a given patient visit were determined using data collected prospectively from 24 Veterans receiving cisplatin. Pure-tone thresholds were examined within an octave of each subjects high-frequency hearing limit. DPOAE were collected as a set of four response growth (input/output) functions near the highest f2 frequency that yielded a robust response at L2 = L1 = 65 dB SPL. Logistic regression modeled the risk of hearing change using several DPOAE metrics, drug treatment factors, and other patient factors as independent variables. An optimal discriminant function was derived by reducing the model so that only statistically significant variables were included. Receiver operating characteristic curve analyses were used to evaluate test performance. Results: At higher cisplatin doses, ears with better hearing at baseline were more likely to exhibit ototoxic hearing changes than those with poorer hearing. Measures of pre-exposure hearing, cumulative drug dose, and DPOAEs generated a highly accurate discriminant function with a cross-validated area under the receiver operating characteristic curve of 0.9. DPOAEs alone also provided an indication of ototoxic hearing change when measured at the highest DPOAE test frequency that yielded a robust response. Conclusions: DPOAEs alone and especially in combination with pre-exposure hearing and cisplatin dose provide an indication of whether or not hearing has changed as a result of cisplatin administration. These promising results need to be validated in a separate sample.

Tinnitus onset rates from chemotherapeutic agents and ototoxic antibiotics: results of a large prospective study.

BACKGROUND AND PURPOSEnTo report on the incidence and relative risk of tinnitus onset from a variety of drug therapies known to be ototoxic. Two main questions were asked: (1) What is the prevalence and incidence of tinnitus among patients treated with cisplatin, carboplatin, or ototoxic antibiotic therapies? (2) Do commonly reported treatment or subject factors confound or modify the incidence of tinnitus onset?nnnDATA COLLECTION AND ANALYSISnA prospective observational study design was used to evaluate occurrence of significant otologic changes in 488 veterans (962 ears) receiving chemotherapeutic agents (cisplatin, carboplatin), ototoxic antibiotics (primarily aminoglycoside), or nonototoxic drugs (control medications). A subset of 260 veterans lacking tinnitus prior to drug exposure was used to compare rates of tinnitus onset. Subjects were tested prior to, during, and following their treatment. Planned comparisons using logistic regression, analysis of variance (ANOVA), and chi(2) statistics were made among groups by the type of medication taken, age, presence of preexisting hearing loss, days on drug, and cumulative dose of drug.nnnRESULTSnBaseline tinnitus rates were high (nearly 47%) relative to the general population of a similar age. Subjects with exposure to ototoxic medications had significantly increased risk for developing tinnitus. Those on chemotherapeutic agents were found to have the greatest risk. Cisplatin elevated the risk by 5.53 times while carboplatin increased the risk by 3.75 over nonototoxic control medications. Ototoxic antibiotics resulted in borderline risk (2.81) for new tinnitus. Contrary to other reports, we did not find that subject factors (increased age or pre-existing hearing loss) or treatment factors (days on drug or cumulative dose) contributed to rates of tinnitus onset during treatment.nnnCONCLUSIONSnThis large prospective study confirms that new tinnitus during treatment is associated with chemotherapy and with certain ototoxic antibiotic treatment. Cisplatin and carboplatin were found to be the most potent ototoxic agents causing tinnitus at much greater numbers than the other drugs studied. Implications for counseling and audiological resource allocation are discussed.

Diabetes-related changes in auditory brainstem responses.

Determine effects on auditory brainstem response (ABR) of diabetes mellitus (DM) severity.

Transient-evoked stimulus-frequency and distortion-product otoacoustic emissions in normal and impaired ears

Transient-evoked stimulus-frequency otoacoustic emissions (SFOAEs), recorded using a nonlinear differential technique, and distortion-product otoacoustic emissions (DPOAEs) were measured in 17 normal-hearing and 10 hearing-impaired subjects using pairs of tone pips (pp), gated tones (gg), and for DPOAEs, continuous and gated tones (cg). Temporal envelopes of stimulus and OAE waveforms were obtained by narrow-band filtering at the stimulus or DP frequency. Mean SFOAE latencies in normal ears at 2.7 and 4.0 kHz decreased with increasing stimulus level and were larger at 4.0 kHz than latencies in impaired ears. Equivalent auditory filter bandwidths were calculated as a function of stimulus level from SFOAE latencies by assuming that cochlear transmission is minimum phase. DPOAE latencies varied less with level than SFOAE latencies. The ppDPOAEs often had two (or more) peaks separated in time with latencies consistent with model predictions for distortion and reflection components. Changes in ppDPOAE latency with level were sometimes explained by a shift in relative amplitudes of distortion and reflection components. The pp SFOAE SPL within the main spectral lobe of the pip stimulus was higher for normal ears in the higher-frequency half of the pip than the lower-frequency half, which is likely an effect of basilar membrane two-tone suppression.

Auditory Brainstem Response Altered in Humans with Noise Exposure Despite Normal Outer Hair Cell Function

Objectives: Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Design: Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6u2009kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. Results: After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Conclusions: Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories.

Hearing Impairment in Relation to Severity of Diabetes in a Veteran Cohort.

Objective: Type 2 diabetes is epidemic among veterans, approaching three times the prevalence of the general population. Diabetes leads to devastating complications of vascular and neurologic malfunction and appears to impair auditory function. Hearing loss prevention is a major health-related initiative in the Veterans Health Administration. Thus, this research sought to identify, and quantify with effect sizes, differences in hearing, speech recognition, and hearing-related quality of life (QOL) measures associated with diabetes and to determine whether well-controlled diabetes diminishes the differences. Design: The authors examined selected cross-sectional data from the baseline (initial) visit of a longitudinal study of Veterans with and without type 2 diabetes designed to assess the possible differences in age-related trajectories of peripheral and central auditory function between the two groups. In addition, the diabetes group was divided into subgroups on the basis of medical diagnosis of diabetes and current glycated hemoglobin (HbA1c) as a metric of disease severity and control. Outcome measures were pure-tone thresholds, word recognition using sentences presented in noise or time-compressed, and an inventory assessing the self-perceived impact of hearing loss on QOL. Data were analyzed from 130 Veterans ages 24 to 73 (mean 48) years with well-controlled (controlled) diabetes, poorly controlled (uncontrolled) diabetes, prediabetes, and no diabetes. Regression was used to identify any group differences in age, noise exposure history, and other sociodemographic factors, and multiple regression was used to model each outcome variable, adjusting for potential confounders. Results were evaluated in relation to diabetes duration, use of insulin (yes, no), and presence of selected diabetes complications (neuropathy and retinopathy). Results: Compared with nondiabetics, Veterans with uncontrolled diabetes had significant differences in hearing at speech frequencies, including poorer hearing by 3 to 3.5 dB for thresholds at 250 Hz and in a clinical pure-tone average, respectively. Compared with nondiabetic controls, individuals with uncontrolled diabetes also significantly more frequently reported that their hearing adversely impacted QOL on one of the three subscales (ability to adapt). Despite this, although they also had slightly poorer mean scores on both word recognition tasks performed, these differences did not reach statistical significance and all subjects performed well on these tasks. Compared with Veterans with controlled diabetes, those with uncontrolled disease tended to have had diabetes longer, be insulin-dependent, and have a greater prevalence of diabetic retinopathy. Results are generally comparable with the literature with regard to the magnitude of threshold differences and the prevalence of hearing impairment but extend prior work by providing threshold difference and hearing loss prevalence effect sizes by category of diabetes control and by including additional functional measures. Conclusions: In a cohort of Veterans with type 2 diabetes and relatively good hearing, significant effects of disease severity were found for hearing thresholds at a subset of frequencies and for one of the three QOL subscales. Significant differences were concentrated among those with poorly controlled diabetes based on current HbA1c. Results provide evidence that the observed hearing dysfunction in type 2 diabetes might be prevented or delayed through tight metabolic control. Findings need to be corroborated using longitudinal assessments.

Relating age and hearing loss to monaural, bilateral, and binaural temporal sensitivity.

Older listeners are more likely than younger listeners to have difficulties in making temporal discriminations among auditory stimuli presented to one or both ears. In addition, the performance of older listeners is often observed to be more variable than that of younger listeners. The aim of this work was to relate age and hearing loss to temporal processing ability in a group of younger and older listeners with a range of hearing thresholds. Seventy-eight listeners were tested on a set of three temporal discrimination tasks (monaural gap discrimination, bilateral gap discrimination, and binaural discrimination of interaural differences in time). To examine the role of temporal fine structure in these tasks, four types of brief stimuli were used: tone bursts, broad-frequency chirps with rising or falling frequency contours, and random-phase noise bursts. Between-subject group analyses conducted separately for each task revealed substantial increases in temporal thresholds for the older listeners across all three tasks, regardless of stimulus type, as well as significant correlations among the performance of individual listeners across most combinations of tasks and stimuli. Differences in performance were associated with the stimuli in the monaural and binaural tasks, but not the bilateral task. Temporal fine structure differences among the stimuli had the greatest impact on monaural thresholds. Threshold estimate values across all tasks and stimuli did not show any greater variability for the older listeners as compared to the younger listeners. A linear mixed model applied to the data suggested that age and hearing loss are independent factors responsible for temporal processing ability, thus supporting the increasingly accepted hypothesis that temporal processing can be impaired for older compared to younger listeners with similar hearing and/or amounts of hearing loss.

Multivariate DPOAE metrics for identifying changes in hearing: Perspectives from ototoxicity monitoring

Abstract Distortion-product otoacoustic emissions (DPOAEs) provide a window into real-time cochlear mechanical function. Yet, relationships between the changes in DPOAE metrics and auditory sensitivity are still poorly understood. Explicating these relationships might support the use of DPOAEs in hearing conservation programs (HCPs) for detecting early damage leading to noise-induced hearing loss (NIHL) so that mitigating steps might be taken to limit any lasting damage. This report describes the development of DPOAE-based statistical models to assess the risk of hearing loss from cisplatin treatment among cancer patients. Ototoxicity risk assessment (ORA) models were constructed using a machine learning paradigm in which partial least squares and leave-one-out cross-validation were applied, yielding optimal screening algorithms from a set of known risk factors for ototoxicity and DPOAE changes from pre-exposure baseline measures. Single DPOAE metrics alone were poorer indicators of the risk of ototoxic hearing shifts than the best performing multivariate models. This finding suggests that multivariate approaches applied to the use of DPOAEs in a HCP, will improve the ability of DPOAE measures to identify ears with noise-induced mechanical damage and/or hearing loss at each monitoring interval. This prediction must be empirically assessed in noise-exposed subjects.