Automated Adaptive Wideband Acoustic Stapedius Reflex Thresholds in Adults With Normal Hearing and Sensorineural Hearing Loss.

OBJECTIVES: This study compared the measurement of the acoustic stapedius reflex threshold (ART) obtained using a traditional method with that obtained using an automated adaptive wideband (AAW) method. Participants included three groups of adults with normal hearing (NH), mild sensorineural hearing loss (SNHL), or moderate SNHL. The purpose of the study was to compare ARTs for the three groups and to determine which method had the best performance in detecting SNHL. DESIGN: Ipsilateral and contralateral ARTs were obtained using 0.5, 1, and 2 kHz tonal activators, and broadband noise (BBN) activators on a traditional admittance system (Clinical) at tympanometric peak pressures (TPP) and on an experimental wideband system using an AAW method at both ambient pressure and TPP. ART data previously reported for 39 NH adults with a mean age of 47.7 years were compared with data for 25 participants with mild SNHL with a mean age of 63.8 years, and 20 participants with moderate SNHL with a mean age of 65.7 years. Differences in ARTs between the normal-hearing and SNHL groups for the three methods were examined using a General Linear Model Repeated-Measures test. A receiver operating characteristic curve (ROC) analysis was also used to determine the ability of an ART test to detect SNHL. RESULTS: For the 0.5 kHz activator condition, there were no significant group mean differences in ART between NH and SNHL groups for either ipsilateral or contralateral activator presentation modes for the Clinical or AAW methods. There were significant group mean differences for the 1 and 2 kHz tonal activators and BBN activator for both ipsilateral and contralateral modes with greater differences in ART between groups for the AAW method than the Clinical method. In these conditions, the mean ART was lower for the AAW tests relative to the Clinical test. The greatest difference between groups was for the ipsilateral AAW tests for the comparison of NH with moderate SNHL for the BBN activator. This difference was approximately 20 dB for the AAW tests and 8 dB for the Clinical test. The ROC analysis showed that the area under the ROC curve (AUC) increased with the frequency of the activator stimulus and with the degree of hearing loss and was maximal for the BBN activator for both the AAW and Clinical methods for both ipsilateral and contralateral presentations. CONCLUSIONS: For ipsilateral and contralateral ART tests for activator frequencies above 0.5 kHz and BBN, listeners with SNHL generally had elevated ARTs compared with those with NH. The AAW method resulted in greater differences between SNHL groups and NH than the Clinical method. The AUC for detecting SNHL also increased with activator frequency and degree of hearing loss and was greatest for the BBN activator for the AAW method in both the ambient and TPP conditions. The results are encouraging for the use of an AAW ART method for the assessment of individuals with SNHL.

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients With Cystic Fibrosis.

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. Supplemental Material https://doi.org/10.23641/asha.16624366.

Incorporating Patient Narratives to Enhance Audiological Care and Clinical Research Outcomes.

Purpose The engagement of patients as key stakeholders in their experience of care processes is a critical component of quality improvement efforts for both clinical care and translational research. Increasingly, health care systems are soliciting input from patients on care processes and experiences through surveys, patient interviews, and patient video narratives. The purpose of this viewpoint article is twofold: (a) to describe the increasing role of patient narratives about their experiences with adverse health conditions to inform patient-centered research and quality improvement efforts and (b) to present three patient narratives that highlight the real-world impacts of hearing loss and tinnitus, the life enhancing impacts of aural rehabilitation, and the importance of prospective ototoxicity monitoring in individuals with complex health conditions. Conclusion Patient narratives provide individual patient perspectives that can be used to build awareness of the range of experiences and impact of hearing disorders, and to explore patient preferences for when and how to implement hearing-related clinical services.

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.

Functional Impacts of Aminoglycoside Treatment on Speech Perception and Extended High-Frequency Hearing Loss in a Pediatric Cystic Fibrosis Cohort.

Purpose The purpose of this study is to better understand the prevalence of ototoxicity-related hearing loss and its functional impact on communication in a pediatric and young adult cohort with cystic fibrosis (CF) and individuals without CF (controls). Method We did an observational, cross-sectional investigation of hearing function in children, teens, and young adults with CF (n = 57, M = 15.0 years) who received intravenous aminoglycoside antibiotics and age- and gender-matched controls (n = 61, M = 14.6 years). Participants completed standard and extended high-frequency audiometry, middle ear measures, speech perception tests, and a hearing and balance questionnaire. Results Individuals with CF were 3-4 times more likely to report issues with hearing, balance, and tinnitus and performed significantly poorer on speech perception tasks compared to controls. A higher prevalence of hearing loss was observed in individuals with CF (57%) compared to controls (37%). CF and control groups had similar proportions of slight and mild hearing losses; however, individuals with CF were 7.6 times more likely to have moderate and greater degrees of hearing loss. Older participants displayed higher average extended high-frequency thresholds, with no effect of age on average standard frequency thresholds. Although middle ear dysfunction has not previously been reported to be more prevalent in CF, this study showed that 16% had conductive or mixed hearing loss and higher rates of previous otitis media and pressure equalization tube surgeries compared to controls. Conclusions Individuals with CF have a higher prevalence of conductive, mixed, and sensorineural hearing loss; poorer speech-in-noise performance; and higher rates of multiple symptoms associated with otologic disorders (tinnitus, hearing difficulty, dizziness, imbalance, and otitis media) compared to controls. Accordingly, children with CF should be asked about these symptoms and receive baseline hearing assessment(s) prior to treatment with potentially ototoxic medications and at regular intervals thereafter in order to provide otologic and audiologic treatment for hearing- and ear-related problems to improve communication functioning.

Effects of Otosclerosis on Middle Ear Function Assessed With Wideband Absorbance and Absorbed Power.

OBJECTIVE: Wideband absorbance and absorbed power were evaluated in a group of subjects with surgically confirmed otosclerosis (Oto group), mean age 51.6 years. This is the first use of absorbed power in the assessment of middle ear disorders. Results were compared with control data from two groups of adults, one with normal hearing (NH group) mean age of 31 years, and one that was age- and sex-matched with the Oto group and had sensorineural hearing loss (SNHL group). The goal was to assess group differences using absorbance and absorbed power, to determine test performance in detecting otosclerosis, and to evaluate preoperative and postoperative test results. DESIGN: Audiometric and wideband tests were performed over frequencies up to 8 kHz. The three groups were compared on wideband tests using analysis of variance to assess group mean differences. Receiver operating characteristic (ROC) curve analysis was also used to assess test accuracy at classifying ears as belonging to the Oto or control groups using the area under the ROC curve (AUC). A longitudinal design was used to compare preoperative and postoperative results at 3 and 6 months. RESULTS: There were significant mean differences in the wideband parameters between the Oto and control groups with generally lower absorbance and absorbed power for the Oto group at ambient and tympanometric peak pressure (TPP) depending on frequency. The SNHL group had more significant differences with the Oto group than did the NH group in the high frequencies for absorbed power at ambient pressure and tympanometric absorbed power at TPP, as well as for the tympanometric tails. The greatest accuracy for classifying ears as being in the Oto group or a control group was for absorbed power at ambient pressure at 0.71 kHz with an AUC of 0.81 comparing the Oto and NH groups. The greatest accuracy for an absorbance measure was for the comparison between the Oto and NH groups for the peak-to-negative tail condition with an AUC of 0.78. In contrast, the accuracy for classifying ears into the control or Oto groups for static acoustic admittance at 226 Hz was near chance performance, which is consistent with previous findings. There were significant mean differences between preoperative and postoperative tests for absorbance and absorbed power. CONCLUSIONS: Consistent with previous studies, wideband absorbance showed better sensitivity for detecting the effects of otosclerosis on middle ear function than static acoustic admittance at 226 Hz. This study showed that wideband absorbed power is similarly sensitive and may perform even better in some instances than absorbance at classifying ears as having otosclerosis. The use of a group that was age- and sex-matched to the Oto group generally resulted in greater differences between groups in the high frequencies for absorbed power, suggesting that age-related norms in adults may be useful for the wideband clinical applications. Absorbance and absorbed power appear useful for monitoring changes in middle ear function following surgery for otosclerosis.

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.

Monitoring neonates for ototoxicity.

OBJECTIVES: Neonates admitted to the neonatal intensive care unit (NICU) are at greater risk of permanent hearing loss compared to infants in well mother and baby units. Several factors have been associated with this increased prevalence of hearing loss, including congenital infections (e.g. cytomegalovirus or syphilis), ototoxic drugs (such as aminoglycoside or glycopeptide antibiotics), low birth weight, hypoxia and length of stay. The aetiology of this increased prevalence of hearing loss remains poorly understood. DESIGN: Here we review current practice and discuss the feasibility of designing improved ototoxicity screening and monitoring protocols to better identify acquired, drug-induced hearing loss in NICU neonates. STUDY SAMPLE: A review of published literature. CONCLUSIONS: We conclude that current audiological screening or monitoring protocols for neonates are not designed to adequately detect early onset of ototoxicity. This paper offers a detailed review of evidence-based research, and offers recommendations for developing and implementing an ototoxicity monitoring protocol for young infants, before and after discharge from the hospital.

Ototoxicity monitoring through the eyes of the treating physician: Perspectives from pulmonology and medical oncology.

OBJECTIVES: Integrating audiological management into the care pathways of clinical specialties that prescribe ototoxic medications for essential, often life-preserving medical care that is critical for early hearing loss identification and remediation. Research shows that successful implementation of a new health service or intervention requires alignment of goals among provider groups, institutional leadership and patients. Thoughtful consideration of the physician's viewpoints about ototoxicity and its implications for treatment planning is, therefore, important for the implementation and enduring success of an ototoxicity monitoring programme (OMP). DESIGN: This discussion paper uses qualitative methods to explore the perspectives of four physicians on OMP provision in their patient populations. STUDY SAMPLE: Three pulmonologists and one oncologist completed the written survey or survey-based interview described in this report. RESULTS: Each physician indicated that (i) ototoxicity is a potential problem for their patients; (ii) monitoring hearing is important to ensure good quality of life among their patients and (iii) treatment modification would be considered if an alternative treatment option were available. The physicians differed in their approaches to ototoxicity monitoring, from routine referrals to audiology, to relying on patient self-referral. CONCLUSION: Physician provider input is needed to optimise monitoring schedules and OMP care coordination with audiology.

Chirp-Evoked Otoacoustic Emissions and Middle Ear Absorbance for Monitoring Ototoxicity in Cystic Fibrosis Patients.

OBJECTIVES: The goal of this study was to investigate the use of transient-evoked otoacoustic emissions (TEOAEs) and middle ear absorbance measurements to monitor auditory function in patients with cystic fibrosis (CF) receiving ototoxic medications. TEOAEs were elicited with a chirp stimulus using an extended bandwidth (0.71 to 8 kHz) to measure cochlear function at higher frequencies than traditional TEOAEs. Absorbance over a wide bandwidth (0.25 to 8 kHz) provides information on middle ear function. The combination of these time-efficient measurements has the potential to identify early signs of ototoxic hearing loss. DESIGN: A longitudinal study design was used to monitor the hearing of 91 patients with CF (median age = 25 years; age range = 15 to 63 years) who received known ototoxic medications (e.g., tobramycin) to prevent or treat bacterial lung infections. Results were compared to 37 normally hearing young adults (median age = 32.5 years; age range = 18 to 65 years) without a history of CF or similar treatments. Clinical testing included 226-Hz tympanometry, pure-tone air-conduction threshold testing from 0.25 to 16 kHz and bone conduction from 0.25 to 4 kHz. Experimental testing included wideband absorbance at ambient and tympanometric peak pressure and TEOAEs in three stimulus conditions: at ambient pressure and at tympanometric peak pressure using a chirp stimulus with constant incident pressure level across frequency and at ambient pressure using a chirp stimulus with constant absorbed sound power across frequency. RESULTS: At the initial visit, behavioral audiometric results indicated that 76 of the 157 ears (48%) from patients with CF had normal hearing, whereas 81 of these ears (52%) had sensorineural hearing loss for at least one frequency. Seven ears from four patients had a confirmed behavioral change in hearing threshold for ≥3 visits during study participation. Receiver operating characteristic curve analyses demonstrated that all three TEOAE conditions were useful for distinguishing CF ears with normal hearing from ears with sensorineural hearing loss, with an area under the receiver operating characteristic curve values ranging from 0.78 to 0.92 across methods for frequency bands from 2.8 to 8 kHz. Case studies are presented to illustrate the relationship between changes in audiometric thresholds, TEOAEs, and absorbance across study visits. Absorbance measures permitted identification of potential middle ear dysfunction at 5.7 kHz in an ear that exhibited a temporary hearing loss. CONCLUSIONS: The joint use of TEOAEs and absorbance has the potential to explain fluctuations in audiometric thresholds due to changes in cochlear function, middle ear function, or both. These findings are encouraging for the joint use of TEOAE and wideband absorbance objective tests for monitoring ototoxicity, particularly, in patients who may be too ill for behavioral hearing tests. Additional longitudinal studies are needed in a larger number of CF patients receiving ototoxic drugs to further evaluate the clinical utility of these measures in an ototoxic monitoring program.

Applying U.S. national guidelines for ototoxicity monitoring in adult patients: perspectives on patient populations, service gaps, barriers and solutions.

OBJECTIVES: To promote establishment of effective ototoxicity monitoring programs (OMPs), this report reviews the U.S. national audiology guidelines in relation to "real world" OMP application. Background is provided on the mechanisms, risks and clinical presentation of hearing loss associated with major classes of ototoxic medications. DESIGN: This is a non-systematic review using PubMed, national and international agency websites, personal communications between ototoxicity experts, and results of unpublished research. Examples are provided of OMPs in various healthcare settings within the U.S. civilian sector, Department of Defense (DoD), and Department of Veterans Affairs (VA). STUDY SAMPLE: The five OMPs compared in this report represent a convenience sample of the programs with which the authors are affiliated. Their opinions were elicited via two semi-structured teleconferences on barriers and facilitators of OMP, followed by a self-administered questionnaire on OMP characteristics and practices, with responses synthesized herein. Preliminary results are provided from an ongoing VA clinical trial at one of these OMP sites. Participants were 40 VA patients who received cisplatin chemotherapy in 2014-2017. The study arms contrast access to care for OMP delivered on the treatment unit versus usual care as provided in the audiology clinic. RESULTS: Protocols of the OMPs examined varied, reflecting their diverse settings. Service delivery concerns included baseline tests missed or completed after the initial treatment, and monitoring tests done infrequently or only after cessation of treatment. Perceived barriers involved logistics related to accessing and testing patients, such as a lack of processes to help patients enter programs, patients' time and scheduling constraints, and inconvenient audiology clinic locations. Use of abbreviated or screening methods facilitated monitoring. CONCLUSIONS: The most effective OMPs integrated audiological management into care pathways of the clinical specialties that prescribe ototoxic medications. More OMP guidance is needed to inform evaluation schedules, outcome reporting, and determination of actionable ototoxic changes. Guidance is also lacking on the use of hearing conservation approaches suitable for the mass testing needed to support large-scale OMP efforts. Guideline adherence might improve with formal endorsement from organizations governing the medical specialty stakeholders in OMP such as oncologists, pulmonologists, infectious disease specialists, ototolaryngologists and pharmacists.

Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.

OBJECTIVE: Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2-15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. METHODS: This was a prospective pilot outcomes study of 82 infants (<37 weeks gestational age) admitted to the NICU at Oregon Health & Science University. An ER-200D sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. RESULTS: The mean level of ambient sound was 62.9 dBA (range 51.8-70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of <45.0 dBA. More than 80% of subjects received gentamicin treatment. The referral rate for (i) AABRs, (frequency range: ∼1000-4000 Hz), was 5%; (ii) DPOAEs with a broad F2 frequency range (2063-10031 Hz) was 39%; (iii) DPOAEs with a low-frequency F2 range (<4172 Hz) was 29%, and (iv) DPOAEs with a high-frequency F2 range (>4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). CONCLUSION: All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding higher frequency DPOAE assessments to existing NICU hearing screening protocols could better identify infants at-risk for ototoxicity.

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.

The cumulative effects of intravenous antibiotic treatments on hearing in patients with cystic fibrosis.

BACKGROUND: Aminoglycosides (AGs) and glycopeptides are antibiotics essential for treating life-threatening respiratory infections in patients with cystic fibrosis (CF). The goal of this study was to examine the effects of cumulative intravenous (IV)-AG (amikacin and/or tobramycin) and/or glycopeptide (vancomycin) dosing on hearing status in patients with CF. METHODS: Hearing thresholds were measured from 0.25 to 16.0kHz, in 81 participants with CF. Participants were categorized into two groups: normal hearing in both ears (≤25dB HL for all frequency bands) or hearing loss (>25dB HL for any frequency band in either ear). Participants were also characterized into quartiles by their cumulative IV-AG (with or without vancomycin) exposure. Dosing was calculated using two strategies: (i) total number of lifetime doses, and (ii) total number of lifetime doses while accounting for the total doses per day. This was referred to as the "weighted" method. RESULTS: Participants in the hearing loss group were significantly older than those in the normal-hearing group. After adjusting for gender and age at the time of hearing test, participants in the two highest-quartile exposure groups were almost 5 X more likely to have permanent sensorineural hearing loss than those in the two lowest-quartile exposure groups. There was a small group of CF patients who had normal hearing despite high exposure to IV-antibiotics. CONCLUSIONS: Cumulative IV-antibiotic dosing has a significant negative effect on hearing sensitivity in patients with CF, when controlling for age and gender effects. A trend for increasing odds of hearing loss was associated with increasing cumulative IV-antibiotic dosing.

Normative Wideband Reflectance, Equivalent Admittance at the Tympanic Membrane, and Acoustic Stapedius Reflex Threshold in Adults.

OBJECTIVES: Wideband acoustic immittance (WAI) measures such as pressure reflectance, parameterized by absorbance and group delay, equivalent admittance at the tympanic membrane (TM), and acoustic stapedius reflex threshold (ASRT) describe middle ear function across a wide frequency range, compared with traditional tests employing a single frequency. The objective of this study was to obtain normative data using these tests for a group of normal-hearing adults and investigate test-retest reliability using a longitudinal design. DESIGN: A longitudinal prospective design was used to obtain normative test and retest data on clinical and WAI measures. Subjects were 13 males and 20 females (mean age = 26 years). Inclusion criteria included normal audiometry and clinical immittance. Subjects were tested on two separate visits approximately 1 month apart. Reflectance and equivalent admittance at the TM were measured from 0.25 to 8.0 kHz under three conditions: at ambient pressure in the ear canal and with pressure sweeps from positive to negative pressure (downswept) and negative to positive pressure (upswept). Equivalent admittance at the TM was calculated using admittance measurements at the probe tip that were adjusted using a model of sound transmission in the ear canal and acoustic estimates of ear-canal area and length. Wideband ASRTs were measured at tympanometric peak pressure (TPP) derived from the average TPP of downswept and upswept tympanograms. Descriptive statistics were obtained for all WAI responses, and wideband and clinical ASRTs were compared. RESULTS: Mean absorbance at ambient pressure and TPP demonstrated a broad band-pass pattern typical of previous studies. Test-retest differences were lower for absorbance at TPP for the downswept method compared with ambient pressure at frequencies between 1.0 and 1.26 kHz. Mean tympanometric peak-to-tail differences for absorbance were greatest around 1.0 to 2.0 kHz and similar for positive and negative tails. Mean group delay at ambient pressure and at TPP were greatest between 0.32 and 0.6 kHz at 200 to 300 µsec, reduced at frequencies between 0.8 and 1.5 kHz, and increased above 1.5 kHz to around 150 µsec. Mean equivalent admittance at the TM had a lower level for the ambient method than at TPP for both sweep directions below 1.2 kHz, but the difference between methods was only statistically significant for the comparison between the ambient method and TPP for the upswept tympanogram. Mean equivalent admittance phase was positive at all frequencies. Test-retest reliability of the equivalent admittance level ranged from 1 to 3 dB at frequencies below 1.0 kHz, but increased to 8 to 9 dB at higher frequencies. The mean wideband ASRT for an ipsilateral broadband noise activator was 12 dB lower than the clinical ASRT, but had poorer reliability. CONCLUSIONS: Normative data for the WAI test battery revealed minor differences for results at ambient pressure compared with tympanometric methods at TPP for reflectance, group delay, and equivalent admittance level at the TM for subjects with middle ear pressure within ±100 daPa. Test-retest reliability was better for absorbance at TPP for the downswept tympanogram compared with ambient pressure at frequencies around 1.0 kHz. Large peak-to-tail differences in absorbance combined with good reliability at frequencies between about 0.7 and 3.0 kHz suggest that this may be a sensitive frequency range for interpreting absorbance at TPP. The mean wideband ipsilateral ASRT was lower than the clinical ASRT, consistent with previous studies. Results are promising for the use of a wideband test battery to evaluate middle ear function.

Effect of sepsis and systemic inflammatory response syndrome on neonatal hearing screening outcomes following gentamicin exposure.

OBJECTIVES: Hearing loss in neonatal intensive care unit (NICU) graduates range from 2% to 15% compared to 0.3% in full-term births, and the etiology of this discrepancy remains unknown. The majority of NICU admissions receive potentially ototoxic aminoglycoside therapy, such as gentamicin, for presumed sepsis. Endotoxemia and inflammation are associated with increased cochlear uptake of aminoglycosides and potentiated ototoxicity in mice. We tested the hypothesis that sepsis or systemic inflammatory response syndrome (SIRS) and intravenous gentamicin exposure increases the risk of hearing loss in NICU admissions. METHODS: The Institutional Review Board at Oregon Health & Science University (OHSU) approved this study design. Two hundred and eight infants met initial criteria, and written, informed consent were obtained from parents or guardians of 103 subjects ultimately enrolled in this study. Prospective data from 91 of the enrolled subjects at OHSU Doernbecher Children's Hospital Neonatal Care Center were processed. Distortion product otoacoustic emissions (DPOAEs; f2 frequency range: 2063-10,031 Hz) were obtained prior to discharge to assess auditory performance. To pass the DPOAE screen, normal responses in >6 of 10 frequencies in both ears were required; otherwise the subject was considered a "referral" for a diagnostic hearing evaluation after discharge. Cumulative dosing data and diagnosis of neonatal sepsis or SIRS were obtained from OHSU's electronic health record system, and the data processed to obtain risk ratios. RESULTS: Using these DPOAE screening criteria, 36 (39.5%) subjects would be referred. Seventy-four (81%) subjects had intravenous gentamicin exposure. Twenty (22%) had ≥4 days of gentamicin, and 71 (78%) had <4 days. The risk ratio (RR) of referral with ≥4 days of gentamicin was 1.92 (p=0.01). Eighteen subjects had sepsis or met neonatal SIRS criteria, 9 of whom had ≥5 days of gentamicin and a DPOAE referral risk ratio of 2.12 (p=0.02) compared to all other subjects. Combining subjects with either vancomycin or furosemide overlap with gentamicin treatment yielded an almost significant risk ratio (RR=1.77, p=0.05) compared to the rest of the cohort. CONCLUSIONS: We report an increased risk of referral with DPOAE screening for those receiving ≥4 days of intravenous gentamicin administration that may contribute to the greater prevalence of hearing loss in NICU graduates. We propose an expanded prospective study to gather a larger cohort of subjects, identifying those with sepsis or neonatal SIRS, to increase the statistical power of this study design. Subsequent studies also need to obtain follow-up diagnostic audiological data to verify whether the outcomes of DPOAE screening, in addition to the standard AABR screen, is a reliable predictor of permanent hearing loss following gentamicin exposure in the NICU.

Sources of variability in wideband energy reflectance measurements in adults.

BACKGROUND: Wideband acoustic immittance measurements of the middle ear, such as wideband energy reflectance (ER), can provide information about how the middle ear functions across the traditional audiometric frequency range. These measurements are being investigated as a new means of evaluating conductive hearing disorders, and studies have been reported on a number of middle-ear disorders. However, the normative database for wideband ER is still being developed, and more information is needed about sources of test variability. PURPOSE: The purpose of the present study was to evaluate sources of variability in wideband ER measurements at baseline and across annual tests for up to 5 yr in subjects with normal hearing. STUDY SAMPLE: The main group consisted of 112 subjects (187 ears), 24 females and 88 males, with normal hearing and normal 0.226-kHz admittance tympanometry. An additional 24 adults with abnormal 0.226-kHz tympanometry provided baseline comparison data. RESEARCH DESIGN: A longitudinal design was used in obtaining annual measurements of audiometry, tympanometry, and wideband ER at ambient pressure in adults. DATA COLLECTION AND ANALYSIS: Clinical audiometry and tympanometry data and 1/3-octave wideband ER measurements were obtained at baseline and annually for up to four additional tests. Descriptive statistics and t-tests were used to explore differences in 1/3-octave baseline ER measures in terms of subject age, test ear, sex, and clinical tympanometry. Longitudinal mixed-effects linear regression models at 1.0, 2.0, and 4.0 kHz were used to examine the different sources of variance affecting ER over time. RESULTS: There were small but statistically significant mean differences in ER for baseline measurements as a function of ear, sex, and age. Compared with these results, data for 29 ears with abnormal 0.226-kHz tympanometry differed from mean normal data across a broad frequency range by as much as 20%. ER varied as a function of peak compensated static acoustic admittance (Ytm) for measures at 1.0 kHz but was unrelated to Ytm at 2.0 and 4.0 kHz. ER also varied as a function of the test ear, with significantly higher ER on the left at 1.0 and 2.0 kHz, but was not significantly related to the test ear at 4.0 kHz. The standard deviation for test-retest variability was about 0.1 at each frequency, which is consistent with previous studies. CONCLUSIONS: Mean wideband ER at baseline showed small but significant differences related to sex, ear, and age. ER was significantly related to Ytm at 1.0 kHz in the longitudinal data but not at 2.0 or 4.0 kHz and to the test ear at 1.0 and 2.0 kHz but not at 4.0 kHz. When evaluated at ambient pressure, ER for ears with negative middle-ear pressure was similar to that of ears with abnormally low Ytm. Therefore it might be necessary to evaluate wideband acoustic immittance compensated for middle-ear pressure by using tympanometry to obtain an effective differential diagnosis of middle-ear disorders in adults.

The MOC reflex during active listening to speech.

PURPOSE: The purpose of this study was to test the hypothesis that active listening to speech would increase medial olivocochlear (MOC) efferent activity for the right vs. the left ear. METHOD: Click-evoked otoacoustic emissions (CEOAEs) were evoked by 60-dB p.e. SPL clicks in 13 normally hearing adults in 4 test conditions for each ear: (a) in quiet; (b) with 60-dB SPL contralateral broadband noise; (c) with words embedded (at -3-dB signal-to-noise ratio [SNR]) in 60-dB SPL contralateral noise during which listeners directed attention to the words; and (d) for the same SNR as in the 3rd condition, with words played backwards. RESULTS: There was greater suppression during active listening compared with passive listening that was apparent in the latency range of 6- to 18-ms poststimulus onset. Ear differences in CEOAE amplitude were observed in all conditions, with right-ear amplitudes larger than those for the left. The absolute difference between CEOAE amplitude in quiet and with contralateral noise, a metric of suppression, was equivalent for right and left ears. When the amplitude differences were normalized, suppression was greater for noise presented to the right and the effect measured for a probe in the left ear. CONCLUSION: The findings support the theory that cortical mechanisms involved in listening to speech affect cochlear function through the MOC efferent system.

TEOAE suppression in adults with learning disabilities.

The presentation of contralateral noise during the recording of transient evoked otoacoustic emissions (TEOAEs) reduces the amplitude of the TEOAE in normally-hearing adults. This is known as TEOAE suppression. The present study investigated TEOAE suppression in 18 adults with learning disabilities (LDs) compared to 18 adults without LDs. TEOAEs were elicited by 60 dB p.e. SPL clicks and were suppressed by the presentation of 60 dB SPL contralateral broadband noise. Suppression was measured as a change in the overall TEOAE response amplitude, and also analysed in 2-ms epochs representing different TEOAE frequency-response bands. A significant interaction was evident between group type and ear tested. Participants in the control group had right ear dominance for the suppression effect, whereas the left ear was found to be dominant for the LD group. These findings suggest a mechanism of the medial olivary cochlear bundle and efferent auditory pathway that differs in those with LD compared to those with typical learning abilities.

Effects of stimulus level on cortical auditory event-related potentials evoked by speech.

The effect of stimulus level on cortical auditory event-related potentials (ERPs) evoked by consonant-vowel (CV) contrasts, /ta/, /da/, and /sa/, was investigated. The lowest level at which CVs were discriminated with >95% accuracy was determined for 15 normally hearing adults. ERPs were obtained at 0, 20, and 40 dB SL above this level during active listening. ERP latencies decreased as level increased. P300 amplitude did not vary with CV level or type; however, obligatory ERPs decreased in amplitude as level increased. The effect of level on P300 latency is likely related to the cognitive processing speed needed to perform speech discrimination. Obligatory ERP amplitude results suggest that attention demands vary with level during discrimination of speech features.