UPPER AIRWAY CONTROL OF TRANSTRACHEAL INSUFFLATION

阻塞性睡眠呼吸暂停的特征是睡眠期间反复出现咽阻塞，并伴有公认的心血管、呼吸和神经认知功能障碍。目前的治疗策略旨在缓解或绕过上呼吸道阻塞部位，但通常无效或耐受性差。在本提案中，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插管（hf-TTI），一种通过薄套管向气管输送气流的方法。基于目前对睡眠时上呼吸道阻塞发病机制的了解，我们利用上呼吸道独特的生理特性来调节hf-TTI给药期间的呼吸模式。利用上呼吸道的斯特林电阻模型，我们将描述控制其特性的机械和反射因素，并建立一个概念框架，用于开发支持睡眠期间通气的新策略。在三个特定目的中，我们分别探讨了htf - tti给药期间上呼吸道的气流动力学，并描述了调节上呼吸道溃散性和流出阻力的机制。在具体目标1中，我们将模拟睡眠中呼吸暂停患者在(a)稳态和(b)动态hf-TTI条件下上呼吸道的生物力学。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，htf - tti的反射反应对上呼吸道塌陷的调节不同。在具体目标3中，我们基于从早期目标中获得的见解，并提出了两种新的hf-TTI通气策略(a)严重上气道阻塞患者和(b)睡眠期间不同程度上气道阻塞的动物。初步提出了优化呼吸暂停患者睡眠时上呼吸道功能和通气的实验。建议在动物身上进行补充研究，以将我们的见解扩展到睡眠时上呼吸道阻塞程度较轻的人类。这些实验将采用标准的生理记录方法。本实验将有助于我们进一步了解上气道阻塞的潜在发病机制，并为支持睡眠呼吸暂停患者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.