Physiological effects of hyperosmotic vocal fold surface fluid

描述(申请人提供)：本申请的目的是测量高渗液环境对声带粘膜生理和发声功能的影响。以往的研究表明，声带的等渗液环境是调节声带粘膜生理和声音产生的必要条件。然而，声带的等渗流体环境很容易受到每天暴露在条件不佳的吸入空气、烟雾和污染物中的干扰。这些扰动增加了高渗透声带表面液中盐类、蛋白质和颗粒的浓度，影响了发声功能和粘膜生理表面液，创造了高渗透环境。来自其他生物组织的数据表明，高渗透表面环境对组织生理是有害的，但高渗透声带表面液(VFSF)对声带粘膜生理和发声功能的影响尚不清楚。这项应用将结合自然组织方案和人体实验来(1)测量高渗透表面液对声带粘膜离子运输和炎症介质产生的影响(2)表征健康受试者和报告发声疲劳的说话者的高渗透VFSF的化学成分，他们在低湿度下完成口头呼吸挑战(3)检查在低湿度下口腔呼吸诱导的高渗透VFSF的生理效应是否在发声阈值压力的临床测量中明显，以及(4)通过湿化吸入空气，证明在口腔呼吸期间诱导的高渗透VFSF的影响被逆转。这些翻译实验将通过证明高渗VFSF在发声疲劳的说话者中持续存在，来研究高渗表面液对声带粘膜生理学的影响的相关性。此外，这一应用将为湿化环境空气在恢复声带局部流体环境中的有益效果提供新的经验证据。提高对VFSF化学成分的了解，以及VFSF在调节黏膜生理学中的作用，对于为有声音问题的个体开发科学的水化治疗和个性化的药理策略至关重要。高渗的声带表面液体是由于日常对局部声带环境的挑战造成的。这项应用将证明，高渗的声带表面液体对粘膜生理有不利影响，是一种促炎应激，但这些有害影响可以通过检查因变量之间的相互依赖关系来预防。鉴于与治疗嗓音问题相关的巨大经济和社会成本，对预防的关注既及时又相关。

DESCRIPTION (provided by applicant): The goal of this application is to measure the effects of hyperosmotic fluid environment on vocal fold mucosal physiology and vocal function. Previous research has suggested that the isosmotic fluid environment of the vocal folds is necessary for regulating vocal fold mucosal physiology and ease of voice production. However, the isosmotic fluid environment of the vocal folds is easily perturbed by everyday exposure to poorly conditioned inhaled air, smoke, and pollutants. These perturbations raise the concentration of salts, proteins, and particulate in the effects of hyperosmotic vocal fold surface fluid on vocal function and mucosal physiology surface fluid, creating a hyperosmotic environment. Data from other biological tissues indicate that a hyperosmotic surface environment is detrimental to tissue physiology, but, the effects of hyperosmotic vocal fold surface fluid (VFSF) on vocal fold mucosal physiology and vocal function are not known. This application will utilize a combination of native tissue protocols and human subject experiments to (1) Measure the effects of hyperosmotic surface fluid on vocal fold mucosal ion transport, and production of inflammatory mediators (2) Characterize the chemical composition of hyperosmotic VFSF in healthy subjects and speakers reporting vocal fatigue, who are completing an oral breathing challenge at low humidity (3) Examine whether the physiological effects of hyperosmotic VFSF induced by oral breathing at low humidity are evident in clinical measures of Phonation Threshold Pressure and (4) Demonstrate reversal of the effects of hyperosmotic VFSF induced during oral breathing, by humidifying inhaled air. These translational experiments will address the relevance of studying the effects of hyperosmotic surface fluid on vocal fold mucosal physiology by demonstrating that hyperosmotic VFSF persists in speakers with vocal fatigue. Further, this application will offer novel empirical evidence for the beneficial effects of humidifying ambient air in restoring the local fluid environment of the vocal folds. Improved understanding of the chemical composition of VFSF, and the role of VFSF in regulating mucosal physiology, are paramount to developing scientifically-grounded hydration treatments, and personalized pharmacological strategies for individuals with voice problems. Hyperosmotic vocal fold surface fluid results from everyday challenges to the local vocal fold environment. This application will demonstrate that hyperosmotic vocal fold surface fluid adversely affects mucosal physiology and is a proinflammatory stress, but that these detrimental effects can be prevented by to examine the interdependencies among the dependent variables. Given the enormous economic and societal costs associated with treating voice problems, the focus on prevention is both timely and relevant.