Early Detection of Noise-Induced Hearing Loss

描述（由申请人提供）： 拟议的更新申请的总体目标是识别畸变产物耳声发射（DPOAE）的特征，最终将改善早期检测噪声性听力损失（NIHL）的临床方法，这是退伍军人遭受的主要感官残疾。为此，两个特殊用途的DPOAE措施，我们称之为增强和残留DP-图，沿着相关的DPOAE水平/相位（L/P）地图将获得在兔子之前和之后的标准化噪声暴露事件。这些DP图将测试这样的概念，即当通过使用干扰音（IT）和矢量减法方法分离f2源和基底源产生的DPOAE时，DPOAE响应空间中的细微噪声后变化可以比它们可以通过常见的标准DP图更灵敏地识别。（见初步研究）发现，兔子和其他常见的实验室物种，不像人类那样有来自DPOAE频率位置（fdp）的“反射发射”。然而，令人费解的是，它们仍然表现出垂直的相位带，这是反射发射的主要特征。使用抑制方法获得DPOAE L/P地图，并没有IT放置在L/P空间内的各种频率位置，存在的基础耳蜗源的DPOAE成立。该基础源被揭示为作为“有IT”和“无IT”DPOAE L/P图之间的矢量差获得的残余DPOAE。术语“增强”图或DP-图被创造来描述当用存在的IT获得时的这些频率函数，在这种条件下，“填充”或“掩蔽”损伤图案的真实程度的基础源被去除。污染的基础源的发现有望修改听力场的当前知识的基本过程的DPOAE产生的耳蜗，也可能导致DPOAE测试，更灵敏地识别NIHL的发病阶段的发展。这种测试也可能是有用的退伍军人，谁是诊所的病人，往往有显着的预先存在的听力损失，在较高水平的主要音调可以用来增加信噪比（SNR），同时保持测试的灵敏度和频率特异性。三个具体的目标将实现设计一个最佳的增强DPOAE测试，并评估其在检测NIHL的效用。第一个目标在模拟NIHL条件下使用第4音测试的假设，即可以确定最有效地去除（抑制）污染的基础源，而不影响f2 DPOAE源的各种主色调水平组合的最佳IT水平。第二个具体目标测试了从具体目标#1的实验中得到的优化的“增强”（f2源）和残余DP-图（基础源）的能力，以识别兔在暂时和永久NIHL条件下的耳蜗损伤程度。这里测试的假设是，增强的DP图将在具有噪声诱导的永久性阈值偏移的兔中揭示比标准DP图预测的更大的耳蜗损伤。最后，第三个具体的目标将测试增强DP-gram引起的更高级别的主要音调，以揭示噪声损伤的耳蜗区域的退伍军人与NIHL的能力。这里检查的概念是，高水平的主要音调将是更有用的条件下，预先存在的听力损失比传统的低水平的初级使用优化的增强DP-gram通过删除基础源，发挥作用，以掩盖受损的耳蜗区域的主要音调水平增加。总之，结合实验将提供一个更完整的了解DPOAE的产生，这将允许创建一个有用的临床测试诊断和监测NIHL的发展。 公共卫生相关性： 听力损失的一个常见原因是暴露于过量的噪音，噪音引起的听力损失（NIHL）是退伍军人最常见的残疾之一。计划中的研究探索了一种新技术，该技术隔离了导致听力终末器官（即耳蜗）产生的失真产物耳声发射的几个来源，耳蜗对噪声暴露的不利影响特别敏感。拟议的研究将有助于设计一种新的临床试验，有望改善NIHL早期阶段的检测。这样的测试将提供一种方法来减少或预防NIHL的军事服务人员，以及约3000万其他美国人，他们经常暴露在工作场所的过度噪音中，以及无数其他人，他们间歇性地暴露在与某些娱乐活动相关的强烈声音中。

DESCRIPTION (provided by applicant): The overall goal of the proposed renewal application is to identify features of distortion product otoacoustic emissions (DPOAEs) that will eventually improve clinical methods for the early detection of noise-induced hearing loss (NIHL), which is a major sensory disability suffered by military veterans, in particular. Toward this end, two special-purpose DPOAE measures, which we have termed augmented and residual DP-grams, along with related DPOAE level/phase (L/P) maps will be obtained in rabbits before and after standardized noise- exposure episodes. These DP-grams will test the notion that subtle post-noise changes in the DPOAE response space can be more sensitively identified when the f2- and basal-source generated DPOAEs are isolated by the use of an interference tone (IT) and vector-subtraction methods than they can be by the common standard DP-gram. During our prior studies, we unexpectedly (see Preliminary Studies) discovered that rabbits, and likely other common laboratory species, do not have 'reflection emissions' arising from the DPOAE frequency place (fdp) as do humans. However, inexplicably, they still exhibit vertical phasing banding, which is a cardinal feature of reflection emissions. Using suppression methods to obtain DPOAE L/P maps with and without an IT placed at various frequency locations within the L/P space, the existence of a basal cochlear source of DPOAEs was established. This basal source was revealed as a residual DPOAE obtained as the vector difference between the 'with-IT' and 'without IT' DPOAE L/P maps. The term 'augmented' maps or DP- grams was coined to describe these frequency functions when obtained with the IT present in that, under this condition, the basal source that 'fills in' or 'masks' the true extent of the damage pattern is removed. The discovery of the contaminating basal source promises to modify the hearing field's current knowledge concerning the fundamental processes underlying DPOAE generation by the cochlea, and may also lead to the development of DPOAE tests that more sensitively identify the onset stages of NIHL. Such tests may also be useful in veterans, who are clinic patients, often with significant preexisting hearing losses, in that higher-level primary tones can be used to increase the signal-to-noise ratio (SNR), while maintaining the test's sensitivity and frequency specificity. Three specific aims will be achieved to devise an optimal augmented DPOAE test and to evaluate its utility in detecting NIHL. The first aim under simulated NIHL conditions using a 4th tone tests the hypothesis that an optimal IT level for various primary-tone level combinations can be identified that most effectively removes (suppresses) the contaminating basal source, without affecting the f2 DPOAE source. The second specific aim tests the ability of the optimized 'augmented' (f2 source) and residual DP-gram (basal source) resulting from the experiments of Specific Aim #1 to identify the extent of cochlear damage under both temporary and permanent NIHL conditions in rabbits. The hypothesis tested here is that the augmented DP- gram will reveal in rabbits with noise-induced permanent threshold shifts a larger cochlear lesion than predicted by standard DP-grams. Finally, the third specific aim will test the ability of augmented DP-grams elicited by higher-level primary tones to uncover noise-damaged cochlear regions in veterans with NIHL. The notion examined here is that high-level primary tones will be more useful under conditions of preexisting hearing loss than conventional low-level primaries using the optimized augmented DP-gram by removing basal sources that come into play to obscure damaged cochlear regions as primary-tone levels are increased. Together, the combined experiments will provide a more complete understanding of the generation of DPOAEs, which will permit the creation of a useful clinical test for diagnosing and monitoring the development of NIHL. PUBLIC HEALTH RELEVANCE: A common cause of hearing loss is exposure to excessive noise with noise-induced hearing loss (NIHL) being one of the most common disabilities in military veterans. The planned research explores a new technique that isolates several sources that contribute to the distortion- product otoacoustic emissions produced by the hearing end organ, ie, the cochlea, which is particularly sensitive to the adverse effects of noise exposure. The proposed studies will help design a new clinical test that promises to improve the detection of the early stages of NIHL. Such a test will provide a means to reduce or prevent NIHL in military service personnel, as well as in about 30 million other Americans, who are regularly exposed to excessive noises in the workplace, and countless others, who are intermittently exposed to intense sounds associated with certain recreational activities.