UPPER AIRWAY CONTROL OF TRANSTRACHEAL INSUFFLATION

阻塞性睡眠呼吸暂停的特征是在睡眠期间反复出现咽部阻塞，并伴有公认的心血管、呼吸和神经认知功能障碍。 目前的治疗策略被设计为缓解或绕过上气道阻塞部位，但通常无效或耐受性差。 在这项建议中，我们概述了一种潜在的新方法，用于治疗呼吸暂停患者的高流量经气管吹入（hf-TTI），一种通过细套管将气流输送到气管的方法。 基于目前对睡眠期间上呼吸道阻塞的发病机制的理解，我们利用上呼吸道的独特生理特性来调节hf-TTI给药期间的呼吸模式。 利用上呼吸道的Starling电阻模型，我们将描述控制其属性的机械和反射因素，并建立一个概念框架，用于开发新的策略，以支持睡眠期间的通气。 在三个特定目标中，我们探索了在hf-TTI给药期间通过上气道的气流动力学，并描绘了调节上气道可膨胀性和流出阻力的机制。 在具体目标1中，我们将对睡眠期间呼吸暂停患者在（a）稳态和（B）动态hf-TTI条件下的上气道生物力学进行建模。 在具体目标2中，我们将探讨为什么在（a）稳定睡眠和（B）过渡睡眠期间，对hf-TTI给药的反射反应会不同地调节上呼吸道通透性。 在具体目标3中，我们建立在从早期目标获得的见解的基础上，并提出了两种新的hf-TTI策略，用于通气（a）严重上气道阻塞的患者和（B）睡眠期间不同程度上气道阻塞的动物。 实验最初被提出来优化睡眠期间呼吸暂停患者的上气道功能和通气。 在动物中的补充研究，建议扩大我们的见解，以人类在睡眠期间的上呼吸道阻塞程度较低。 将使用标准生理记录方法进行这些实验。 这些实验将有助于我们进一步了解上呼吸道阻塞的潜在发病机制，并为睡眠呼吸暂停患者支持通气的新方法奠定基础。

Obstructive sleep apnea is characterized by recurrent periods of pharyngeal occlusion during sleep with recognized cardiovascular, respiratory and neurocognitive dysfunction. Current treatment strategies have been designed to either relieve or bypass the site of upper airway obstruction, but are often ineffective or poorly tolerated. In this proposal, we outline a potentially novel approach for treating apneic patients with high flow transtracheal insufflation (hf-TTI), a method for delivering airflow to the trachea through a thin cannula. Based on current understanding of the pathogenesis of upper airway obstruction during sleep, we take advantage of the unique physiologic properties of the upper airways to regulate breathing patterns during hf-TTI administration. Utilizing a Starling resistor model of the upper airways, we will characterize the mechanical and reflex factors that control their properties, and build a conceptual framework for developing new strategies to support ventilation during sleep. In each of three Specific Aims, we explore airflow dynamics through the upper airway during hf-TTI administration and delineate the mechanisms which modulate upper airway collapsibility and outflow resistance. In Specific Aim 1, we will model the biomechanics of the upper airway under (a) steady-state and (b) dynamic hf-TTI conditions in apneic patients during sleep. In Specific Aim 2, we will explore why reflex responses to hf-TTI administration modulate upper airway collapsibility differently during (a) stable and (b) transitional sleep. In Specific Aim 3, we build upon insights gained from the earlier aims, and propose two novel hf-TTI strategies for ventilating (a) patients with severe upper airway obstruction and (b) animals with varying degrees of upper airway obstruction during sleep. Experiments are proposed initially to optimize upper airway function and ventilation in apneic patients during sleep. Complementary studies in animals are proposed to extend our insights to humans with lesser degrees of upper airway obstruction during sleep. Standard physiologic recording methods will be utilized to perform these experiments. The proposed experiments will serve to further our understanding of the underlying pathogenesis of upper airway obstruction as well as build the foundation for novel approaches to support ventilation in sleeping apneic patients.