Physiological effects of hyperosmotic vocal fold surface fluid

描述（由申请人提供）：本申请的目的是测量高渗液体环境对声带粘膜生理和声带功能的影响。以往的研究表明，声带的等渗流体环境是调节声带粘膜生理和发声的必要条件。然而，声带的等渗流体环境很容易受到日常暴露于条件不良的吸入空气，烟雾和污染物的干扰。这些扰动提高了高渗透性声带表面液对声带功能和粘膜生理表面液的影响中的盐、蛋白质和微粒的浓度，形成了高渗透性环境。来自其他生物组织的数据表明，高渗透性表面环境对组织生理有害，但高渗透性声带表面液（VFSF）对声带粘膜生理和声带功能的影响尚不清楚。该应用程序将利用天然组织协议和人体受试者实验的组合来(1)测量高渗透性表面液体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声带疲劳的说话者的高渗透性VFSF的化学成分。(3)检查低湿度口腔呼吸诱导的高渗透性VFSF的生理效应是否在发音阈压的临床测量中明显；(4)通过加湿吸入空气证明口腔呼吸诱导的高渗透性VFSF的逆转作用。这些转化实验将通过证明高渗透性VFSF在声带疲劳的说话者中持续存在，来解决研究高渗透性表面液体对声带粘膜生理学影响的相关性。此外，该应用将为加湿环境空气在恢复声带局部流体环境中的有益作用提供新的经验证据。更好地了解VFSF的化学成分，以及VFSF在调节粘膜生理中的作用，对于开发科学的水化治疗和个性化的语音问题药物策略至关重要。高渗透性声带表面液体是由于日常对局部声带环境的挑战造成的。本应用将证明高渗透性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性来预防。鉴于治疗声音问题需要付出巨大的经济和社会成本，因此重视预防既及时又有意义。

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.