National Center for Rehabilitative Auditory Research (NCRAR), VA Portland Health Care System, OR.
Department of Otolaryngology-Head & Neck Surgery, Oregon Health & Science University, Portland.
Am J Audiol. 2021 Oct 11;30(3S):825-833. doi: 10.1044/2020_AJA-20-00117. Epub 2021 Mar 4.
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.
目的 患有囊性纤维化 (CF) 的个体常接受静脉 (IV) 氨基糖苷 (AG) 抗生素治疗以控制危及生命的细菌感染。临床前动物数据表明,除了损害耳蜗毛细胞外,此类抗生素还可能引起耳蜗突触病和/或损害更高的听觉结构。声反射生长功能 (ARGF) 是听觉系统中神经功能的一种非侵入性、客观的测量方法。在啮齿动物和人类研究中,由于噪声暴露导致的突触病与 ARGF 变浅(中耳功能随刺激水平增加而发生的反射诱导变化较小)有关。在这项研究中,获得了听力正常的 CF 患者的 ARGF,其中一些患者接受了 IV AG 治疗,以及一个没有 CF 的对照组。假设是由于耳毒性引起的耳蜗突触病,接受 IV-AG 暴露的患者会出现 ARGF 变浅。方法 在四组听力正常的参与者中检查了宽带 ARGF:一个没有 CF 的对照组 29 人;以及根据终生 IV-AG 暴露情况分组的 57 名 CF 患者:15 名无暴露,21 名低暴露,21 名高暴露。程序包括纯音测听、临床阻抗、宽带声阻抗电池,包括 ARGF 和瞬态诱发耳声发射。结果 与对照组和无 IV-AG 暴露的 CF 参与者相比,具有正常纯音阈值且终生 IV-AG 暴露较高或较低的 CF 受试者的 ARGF 增强。各组的瞬态诱发耳声发射信号噪声比无差异。结论 这些结果与噪声诱导的耳蜗突触病研究中观察到的 ARGF 变浅模式不同,提示 AG 诱导的耳毒性患者存在听觉功能障碍的中枢机制。