Le Prell C G, Johnson A C, Lindblad A C, Skjönsberg A, Ulfendahl M, Guire K, Green G E, Campbell K C M, Miller J M
Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL, USA.
Noise Health. 2011 Nov-Dec;13(55):432-43. doi: 10.4103/1463-1741.90317.
Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.
噪声性听力损失(NIHL)是一个重大的临床、社会和经济问题。开发新型治疗药物以减少NIHL可能会使大量受噪声影响的人群受益。氧化应激已被确定为噪声诱导感觉细胞死亡和NIHL的一个重要因素,目前已经提出了几种抗氧化策略,有望转化应用于人类受试者。其中一种策略是β-胡萝卜素、维生素C和E以及镁的组合,该组合在啮齿动物模型中已显示出预防NIHL的前景,并且正在一系列国际人体临床试验中进行评估,这些试验采用临时(军事枪炮声、使用音频播放器)和永久性(冲压工厂、军事空军基地)阈移模型(NCT00808470)。本报告中描述的最近完成的瑞典军事枪炮声研究中使用的噪声暴露,平均而言,以传统纯音阈值和畸变产物耳声发射(DPOAE)幅度作为指标,并未导致听觉功能出现可测量的变化。然而,对血浆样本的分析证实,口服活性临床用品2小时后,血液中的含量显著升高,表明该剂量是合理的。血浆检测结果令人鼓舞,但任何新型治疗方法能否被临床接受,关键取决于能否在随机、安慰剂对照的前瞻性人体临床试验中证明该药物能减少噪声诱导的阈移。虽然这种噪声刺激并未导致听力损失,但该试验设计和研究方案可应用于其他受到不同噪声刺激的人群。