Pittsburgh Hearing Research Center and Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
J Assoc Res Otolaryngol. 2019 Apr;20(2):115-131. doi: 10.1007/s10162-018-00709-9. Epub 2019 Mar 1.
In this position review, we propose to establish a path for replacing the empirical classification of tinnitus with a taxonomy from precision medicine. The goal of a classification system is to understand the inherent heterogeneity of individuals experiencing and suffering from tinnitus and to identify what differentiates potential subgroups. Identification of different patient subgroups with distinct audiological, psychophysical, and neurophysiological characteristics will facilitate the management of patients with tinnitus as well as the design and execution of drug development and clinical trials, which, for the most part, have not yielded conclusive results. An alternative outcome of a precision medicine approach in tinnitus would be that additional mechanistic phenotyping might not lead to the identification of distinct drivers in each individual, but instead, it might reveal that each individual may display a quantitative blend of causal factors. Therefore, a precision medicine approach towards identifying these causal factors might not lead to subtyping these patients but may instead highlight causal pathways that can be manipulated for therapeutic gain. These two outcomes are not mutually exclusive, and no matter what the final outcome is, a mechanistic-driven precision medicine approach is a win-win approach for advancing tinnitus research and treatment. Although there are several controversies and inconsistencies in the tinnitus field, which will not be discussed here, we will give a few examples, as to how the field can move forward by exploring the major neurophysiological tinnitus models, mostly by taking advantage of the common features supported by all of the models. Our position stems from the central concept that, as a field, we can and must do more to bring studies of mechanisms into the realm of neuroscience.
在本次位置审查中，我们建议建立一条路径，用精准医学的分类法取代耳鸣的经验分类。分类系统的目标是理解经历和受耳鸣困扰的个体的固有异质性，并确定区分潜在亚组的因素。识别具有不同听力学、心理物理学和神经生理学特征的不同患者亚组将有助于耳鸣患者的管理，以及药物开发和临床试验的设计和执行，而这些临床试验在很大程度上尚未得出明确的结果。精准医学方法在耳鸣中的另一个结果可能是，额外的机制表型不一定会在每个个体中识别出不同的驱动因素，而是可能表明每个个体可能表现出因果因素的定量混合。因此，精准医学方法识别这些因果因素可能不会导致对这些患者进行亚组化，但可能会突出可以为治疗收益而操纵的因果途径。这两种结果并不相互排斥，无论最终结果如何，一种基于机制的精准医学方法都是推进耳鸣研究和治疗的双赢方法。尽管耳鸣领域存在一些争议和不一致之处，这里不会讨论，但我们将举几个例子，说明如何通过探索主要的神经生理学耳鸣模型来推进该领域，主要是利用所有模型都支持的共同特征。我们的立场源于一个核心概念，即作为一个领域，我们可以而且必须做更多的工作，将机制研究纳入神经科学领域。
