National Center for Rehabilitative Auditory Research (NCRAR), VA Portland Health Care System, Portland, Oregon, USA.
Ear Hear. 2018 Jan/Feb;39(1):69-84. doi: 10.1097/AUD.0000000000000464.
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.
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.
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.
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.
本研究旨在探讨瞬态诱发耳声发射(TEOAEs)和中耳吸声测量在接受耳毒性药物治疗的囊性纤维化(CF)患者中监测听觉功能的应用。TEOAEs 使用扩展带宽(0.71 至 8 kHz)的啁啾刺激来诱发,以比传统 TEOAEs 更高的频率测量耳蜗功能。宽带(0.25 至 8 kHz)的吸声提供中耳功能信息。这些高效测量的结合有可能识别出耳毒性听力损失的早期迹象。
使用纵向研究设计监测 91 名接受已知耳毒性药物(如妥布霉素)预防或治疗肺部细菌感染的 CF 患者(中位年龄=25 岁;年龄范围=15 至 63 岁)的听力。结果与 37 名听力正常的年轻成年人(中位年龄=32.5 岁;年龄范围=18 至 65 岁)进行了比较,这些成年人没有 CF 或类似治疗的病史。临床测试包括 226-Hz 鼓室图、0.25 至 16 kHz 的纯音空气传导阈值测试以及 0.25 至 4 kHz 的骨传导测试。实验测试包括在环境和鼓室图峰压下的宽带吸声以及 TEOAEs 在三种刺激条件下:在环境压力和鼓室图峰压下使用具有恒定入射压力水平的啁啾刺激,以及在环境压力下使用具有恒定吸收声功率的啁啾刺激频率。
在初次就诊时,行为听力测试结果表明,157 只耳朵中有 76 只(48%)来自 CF 患者的耳朵听力正常,而这些耳朵中有 81 只(52%)至少有一个频率的感音神经性听力损失。在研究过程中,有 4 名患者的 7 只耳朵出现了≥3 次听力阈值的行为改变。受试者工作特征曲线分析表明,所有三种 TEOAE 条件都可用于区分具有正常听力的 CF 耳朵和具有感音神经性听力损失的耳朵,对于从 2.8 到 8 kHz 的频带,方法之间的受试者工作特征曲线下面积值范围为 0.78 至 0.92。案例研究说明了在研究过程中,听力阈值、TEOAEs 和吸声之间的关系。吸声测量允许在表现出暂时听力损失的耳朵中在 5.7 kHz 处识别潜在的中耳功能障碍。
TEOAEs 和吸声的联合使用有可能解释由于耳蜗功能、中耳功能或两者的变化导致的听力阈值波动。这些发现对于 TEOAE 和宽带吸声客观测试联合用于监测耳毒性,特别是对于那些可能因行为听力测试而病情过重的患者来说,是令人鼓舞的。需要在接受耳毒性药物治疗的更多 CF 患者中进行更多的纵向研究,以进一步评估这些措施在耳毒性监测计划中的临床应用。