Wideband Acoustic Reflex Growth in Adults With Cystic Fibrosis.

Purpose Individuals with cystic fibrosis (CF) are often treated with intravenous (IV) aminoglycoside (AG) antibiotics to manage life-threatening bacterial infections. Preclinical animal data suggest that, in addition to damaging cochlear hair cells, this class of antibiotics may cause cochlear synaptopathy and/or damage to higher auditory structures. The acoustic reflex growth function (ARGF) is a noninvasive, objective measure of neural function in the auditory system. A shallow ARGF (small reflex-induced changes in middle ear function with increasing elicitor level) has been associated with synaptopathy due to noise exposure in rodent and human studies. In this study, the ARGF was obtained in CF patients with normal hearing, some of whom have been treated with IV AGs, and a control group without CF. The hypothesis was that patients with IV-AG exposure would have a shallow ARGF due to cochlear synaptopathy caused by ototoxicity. Method Wideband ARGFs were examined in four groups of normal-hearing participants: a control group of 29 individuals without CF; and in 57 individuals with CF grouped by lifetime IV-AG exposure: 15 participants with no exposure, 21 with low exposure, and 21 with high exposure. Procedures included pure-tone audiometry, clinical immittance, wideband acoustic immittance battery, including ARGFs, and transient evoked otoacoustic emissions. Results CF subjects with normal pure-tone thresholds and either high or low lifetime IV-AG exposure had enhanced ARGFs compared to controls and CF participants without IV-AG exposure. The groups did not differ in transient evoked otoacoustic emission signal-to-noise ratio. Conclusion These results diverge from the shallow ARGF pattern observed in studies of noise-induced cochlear synaptopathy and are suggestive of a central mechanism of auditory dysfunction in patients with AG-induced ototoxicity.

High frequency transient-evoked otoacoustic emission measurements using chirp and click stimuli.

Transient-evoked otoacoustic emissions (TEOAEs) at high frequencies are a non-invasive physiological test of basilar membrane mechanics at the basal end, and have clinical potential to detect risk of hearing loss related to outer-hair-cell dysfunction. Using stimuli with constant incident pressure across frequency, TEOAEs were measured in experiment 1 at low frequencies (0.7-8 kHz) and high frequencies (7.1-14.7 kHz) in adults with normal hearing up to 8 kHz and varying hearing levels from 9 to 16 kHz. In combination with click stimuli, chirp stimuli were used with slow, medium and fast sweep rates for which the local frequency increased or decreased with time. Chirp TEOAEs were transformed into equivalent click TEOAEs by inverse filtering out chirp stimulus phase, and analyzed similarly to click TEOAEs. To improve detection above 8 kHz, TEOAEs were measured in experiment 2 with higher-level stimuli and longer averaging times. These changes increased the TEOAE signal-to-noise ratio (SNR) by 10 dB. Slower sweep rates were investigated but the elicited TEOAEs were detected in fewer ears compared to faster rates. Data were acquired in adults and children (age 11-17 y), including children with cystic fibrosis (CF) treated with ototoxic antibiotics. Test-retest measurements revealed satisfactory repeatability of high-frequency TEOAE SNR (median of 1.3 dB) and coherence synchrony measure, despite small test-retest differences related to changes in forward and reverse transmission in the ear canal. The results suggest the potential use of such tests to screen for sensorineural hearing loss, including ototoxic loss. Experiment 2 was a feasibility study to explore TEOAE test parameters that might be used in a full-scale study to screen CF patients for risk of ototoxic hearing loss.

Pressurized transient otoacoustic emissions measured using click and chirp stimuli.

Transient-evoked otoacoustic emission (TEOAE) responses were measured in normal-hearing adult ears over frequencies from 0.7 to 8 kHz, and analyzed with reflectance/admittance data to measure absorbed sound power and the tympanometric peak pressure (TPP). The mean TPP was close to ambient. TEOAEs were measured in the ear canal at ambient pressure, TPP, and fixed air pressures from 150 to -200 daPa. Both click and chirp stimuli were used to elicit TEOAEs, in which the incident sound pressure level was constant across frequency. TEOAE levels were similar at ambient and TPP, and for frequencies from 0.7 to 2.8 kHz decreased with increasing positive and negative pressures. At 4-8 kHz, TEOAE levels were larger at positive pressures. This asymmetry is possibly related to changes in mechanical transmission through the ossicular chain. The mean TEOAE group delay did not change with pressure, although small changes were observed in the mean instantaneous frequency and group spread. Chirp TEOAEs measured in an adult ear with Eustachian tube dysfunction and TPP of -165 daPa were more robust at TPP than at ambient. Overall, results demonstrate the feasibility and clinical potential of measuring TEOAEs at fixed pressures in the ear canal, which provide additional information relative to TEOAEs measured at ambient pressure.

Assessing Sensorineural Hearing Loss Using Various Transient-Evoked Otoacoustic Emission Stimulus Conditions.

OBJECTIVES: An important clinical application of transient-evoked otoacoustic emissions (TEOAEs) is to evaluate cochlear outer hair cell function for the purpose of detecting sensorineural hearing loss (SNHL). Double-evoked TEOAEs were measured using a chirp stimulus, in which the stimuli had an extended frequency range compared to clinical tests. The present study compared TEOAEs recorded using an unweighted stimulus presented at either ambient pressure or tympanometric peak pressure (TPP) in the ear canal and TEOAEs recorded using a power-weighted stimulus at ambient pressure. The unweighted stimulus had approximately constant incident pressure magnitude across frequency, and the power-weighted stimulus had approximately constant absorbed sound power across frequency. The objective of this study was to compare TEOAEs from 0.79 to 8 kHz using these three stimulus conditions in adults to assess test performance in classifying ears as having either normal hearing or SNHL. DESIGN: Measurements were completed on 87 adult participants. Eligible participants had either normal hearing (N = 40; M F = 16 24; mean age = 30 years) or SNHL (N = 47; M F = 20 27; mean age = 58 years), and normal middle ear function as defined by standard clinical criteria for 226-Hz tympanometry. Clinical audiometry, immittance, and an experimental wideband test battery, which included reflectance and TEOAE tests presented for 1-min durations, were completed for each ear on all participants. All tests were then repeated 1 to 2 months later. TEOAEs were measured by presenting the stimulus in the three stimulus conditions. TEOAE data were analyzed in each hearing group in terms of the half-octave-averaged signal to noise ratio (SNR) and the coherence synchrony measure (CSM) at frequencies between 1 and 8 kHz. The test-retest reliability of these measures was calculated. The area under the receiver operating characteristic curve (AUC) was measured at audiometric frequencies between 1 and 8 kHz to determine TEOAE test performance in distinguishing SNHL from normal hearing. RESULTS: Mean TEOAE SNR was ≥8.7 dB for normal-hearing ears and ≤6 dB for SNHL ears for all three stimulus conditions across all frequencies. Mean test-retest reliability of TEOAE SNR was ≤4.3 dB for both hearing groups across all frequencies, although it was generally less (≤3.5 dB) for lower frequencies (1 to 4 kHz). AUCs were between 0.85 and 0.94 for all three TEOAE conditions at all frequencies, except for the ambient TEOAE condition at 2 kHz (0.82) and for all TEOAE conditions at 5.7 kHz with AUCs between 0.78 and 0.81. Power-weighted TEOAE AUCs were significantly higher (p < 0.05) than ambient TEOAE AUCs at 2 and 2.8 kHz, as was the TPP TEOAE AUC at 2.8 kHz when using CSM as the classifier variable. CONCLUSIONS: TEOAEs evaluated in an ambient condition, at TPP and in a power-weighted stimulus condition, had good test performance in identifying ears with SNHL based on SNR and CSM in the frequency range from 1 to 8 kHz and showed good test-retest reliability. Power-weighted TEOAEs showed the best test performance at 2 and 2.8 kHz. These findings are encouraging as a potential objective clinical tool to identify patients with cochlear hearing loss.

Aural Acoustic Stapedius-Muscle Reflex Threshold Procedures to Test Human Infants and Adults.

Power-based procedures are described to measure acoustic stapedius-muscle reflex threshold and supra-threshold responses in human adult and infant ears at frequencies from 0.2 to 8 kHz. The stimulus set included five clicks in which four pulsed activators were placed between each pair of clicks, with each stimulus set separated from the next by 0.79 s to allow for reflex decay. Each click response was used to detect the presence of reflex effects across frequency that were elicited by a pulsed broadband-noise or tonal activator in the ipsilateral or contralateral test ear. Acoustic reflex shifts were quantified in terms of the difference in absorbed sound power between the initial baseline click and the later four clicks in each set. Acoustic reflex shifts were measured over a 40-dB range of pulsed activators, and the acoustic reflex threshold was objectively calculated using a maximum 10 likelihood procedure. To illustrate the principles underlying these new reflex tests, reflex shifts in absorbed sound power and absorbance are presented for data acquired in an adult ear with normal hearing and in two infant ears in the initial and follow-up newborn hearing screening exams, one with normal hearing and the other with a conductive hearing loss. The use of absorbed sound power was helpful in classifying an acoustic reflex shift as present or absent. The resulting reflex tests are in use in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function in infant and adult ears.

Longitudinal development of wideband reflectance tympanometry in normal and at-risk infants.

PURPOSE: The goals of this study were to measure normal characteristics of ambient and tympanometric wideband acoustic reflectance, which was parameterized by absorbance and group delay, in newborns cared for in well-baby and Neonatal Intensive Care Unit (NICU) nurseries, and to characterize the normal development of reflectance over the first year after birth in a group of infants with clinically normal hearing status followed longitudinally from birth to one year of age. METHODS: Infants were recruited from a well-baby and NICU nursery, passed newborn otoacoustic emissions (OAE) and automated auditory brainstem response (ABR) tests as well as follow-up diagnostic ABR and audiometry. They were tested longitudinally for up to one year using a wideband middle ear acoustic test battery consisting of tympanometry and ambient-pressure tests. Results were analyzed for ambient reflectance across frequency and tympanometric reflectance across frequency and pressure. RESULTS: Wideband absorbance and group delay showed large effects of age in the first 6 months. Immature absorbance and group delay patterns were apparent in the low frequencies at birth and one month, but changed substantially to a more adult-like pattern by age 6 months for both ambient and tympanometric variables. Area and length of the ear canal estimated acoustically increased up to age 1 year. Effects of race (African American and others compared to Caucasian) were found in combination with age effects. Mean and confidence intervals are provided for use as a normative longitudinal database for newborns and infants up to one year of age, for both well-baby and NICU infants.

Air and Bone Conduction Click and Tone-Burst Auditory Brainstem Thresholds Using Kalman Adaptive Processing in Nonsedated Normal-Hearing Infants.

OBJECTIVES: To study normative thresholds and latencies for click and tone-burst auditory brainstem response (TB-ABR) for air and bone conduction in normal infants and those discharged from neonatal intensive care units, who passed newborn hearing screening and follow-up distortion product otoacoustic emission. An evoked potential system (Vivosonic Integrity) that incorporates Bluetooth electrical isolation and Kalman-weighted adaptive processing to improve signal to noise ratios was employed for this study. Results were compared with other published data. DESIGN: One hundred forty-five infants who passed two-stage hearing screening with transient-evoked otoacoustic emission or automated auditory brainstem response were assessed with clicks at 70 dB nHL and threshold TB-ABR. Tone bursts at frequencies between 500 and 4000 Hz were used for air and bone conduction auditory brainstem response testing using a specified staircase threshold search to establish threshold levels and wave V peak latencies. RESULTS: Median air conduction hearing thresholds using TB-ABR ranged from 0 to 20 dB nHL, depending on stimulus frequency. Median bone conduction thresholds were 10 dB nHL across all frequencies, and median air-bone gaps were 0 dB across all frequencies. There was no significant threshold difference between left and right ears and no significant relationship between thresholds and hearing loss risk factors, ethnicity, or gender. Older age was related to decreased latency for air conduction. Compared with previous studies, mean air conduction thresholds were found at slightly lower (better) levels, while bone conduction levels were better at 2000 Hz and higher at 500 Hz. Latency values were longer at 500 Hz than previous studies using other instrumentation. Sleep state did not affect air or bone conduction thresholds. CONCLUSIONS: This study demonstrated slightly better wave V thresholds for air conduction than previous infant studies. The differences found in the present study, while statistically significant, were within the test step size of 10 dB. This suggests that threshold responses obtained using the Kalman weighting software were within the range of other published studies using traditional signal averaging, given step-size limitations. Thresholds were not adversely affected by variable sleep states.

Procedures for ambient-pressure and tympanometric tests of aural acoustic reflectance and admittance in human infants and adults.

Procedures are described to measure acoustic reflectance and admittance in human adult and infant ears at frequencies from 0.2 to 8 kHz. Transfer functions were measured at ambient pressure in the ear canal, and as down- or up-swept tympanograms. Acoustically estimated ear-canal area was used to calculate ear reflectance, which was parameterized by absorbance and group delay over all frequencies (and pressures), with substantial data reduction for tympanograms. Admittance measured at the probe tip in adults was transformed into an equivalent admittance at the eardrum using a transmission-line model for an ear canal with specified area and ear-canal length. Ear-canal length was estimated from group delay around the frequency above 2 kHz of minimum absorbance. Illustrative measurements in ears with normal function are described for an adult, and two infants at 1 month of age with normal hearing and a conductive hearing loss. The sensitivity of this equivalent eardrum admittance was calculated for varying estimates of area and length. Infant-ear patterns of absorbance peaks aligned in frequency with dips in group delay were explained by a model of resonant canal-wall mobility. Procedures will be applied in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function.

Wideband reflectance in newborns: normative regions and relationship to hearing-screening results.

OBJECTIVES: To develop normative data for wideband middle-ear reflectance in a newborn hearing-screening population and to compare test performance with 1-kHz tympanometry for prediction of otoacoustic emission (OAE) screening outcome. DESIGN: Wideband middle-ear reflectance (using both tone and chirp stimuli from 0.2 to 6 kHz), 1-kHz tympanometry, and distortion-product (DP) OAEs were measured in 324 infants at two test sites. Ears were categorized into DP pass and DP refer groups. RESULTS: Normative reflectance values were defined over various frequency regions for both tone and chirp stimuli in ambient pressure conditions, and for reflectance area indices integrated over various frequency ranges. Receiver operating characteristic analyses showed that reflectance provides the best discriminability of DP status in frequency ranges involving 2 kHz and greater discriminability of DP status than 1-kHz tympanometry. Repeated-measures analyses of variance established that (a) there were significant differences in reflectance as a function of DP status and frequency but not sex or ear; (b) tone and chirp stimulus reflectance values are essentially indistinguishable; and (c) newborns from two geographic sites had similar reflectance patterns above 1 kHz. Birth type and weight did not contribute to differences in reflectance. CONCLUSIONS: Referrals in OAE-based infant hearing screening were strongly associated with increased wideband reflectance, suggesting middle-ear dysfunction at birth. Reflectance improved significantly during the first 4 days after birth with normalization of middle-ear function. Reflectance scores can be achieved within seconds using the same equipment used for OAE screening. Newborns with high reflectance scores at stage I screening should be rescreened within a few hours to a few days, because most middle-ear problems are transient and resolve spontaneously. If reflectance and OAE are not passed upon stage II screening, referral to an otologist for ear examination is suggested along with diagnostic testing. Newborns with normal reflectance and a refer result for the OAE screen should be referred immediately to an audiologist for diagnostic testing with threshold auditory brainstem response because of higher risk for permanent hearing loss.

Otoacoustic emissions and tympanometry screening among 0-5 year olds.

OBJECTIVES: To determine the rate of otitis media (OM)-associated transient evoked otoacoustic emissions (TEOAE) screening failure in a sample of preschool children, to evaluate concordance between TEOAE and tympanometry, to investigate risk factors for TEOAE failure, and to determine agreement between TEOAE failure and physician findings at referral. STUDY DESIGN: Cross-sectional. METHODS: Children from birth to 5 years underwent screening by TEOAE and tympanometry, and those with one or more abnormal test result(s) were referred to their physician for further evaluation. Univariate associations between risk factors and TEOAE failure were determined using chi-square analysis. Multiple logistic regression analysis was done to examine the relationship between specific risk factors and TEOAE failure. RESULTS: A total of 664 children aged 2 weeks to 71 months were screened between September 1997 and May 1999. TEOAE and tympanometry failure was found in 25% and 35% of all subjects, respectively. The overall prevalence of OM-associated hearing loss was 20%. Agreement between tympanometry and TEOAE was better for the youngest (<6 mo) and oldest > or =36 mo) age groups. Of those who failed TEOAE, a physician saw 81% within 3 months, and 80% of these had a diagnosis consistent with hearing loss but only 18% had audiometric testing. Sibling history of OM was the only significant predictor for TEOAE failure. CONCLUSIONS: TEOAE screening failure was highly consistent with physician diagnosis at follow-up. Failure of TEOAE in a screening program should be followed with diagnostic audiology testing to determine whether conductive or sensorineural hearing loss is present.