Treatment of Sleep Apnea using a Positive Airway Pressure Rebreathing Modulator

使用气道正压再呼吸调节器治疗睡眠呼吸暂停

• 批准号: 8200404
• 负责人: MATTHEW D. TARLER
• 金额: $ 28.42万
• 依托单位: CLEVELAND MEDICAL DEVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-09 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8200404
• 关键词: Acute; Admixture; Affect; Air; Air Pressure; Apnea; Attention; Back; Breathing; Carbon Dioxide; Central Sleep Apnea; Characteristics; Chronic; Clinical; Clinical Research; Complex; Congestive Heart Failure; Device Designs; Device or Instrument Development; Devices; Diagnostic; Disease; Environmental air flow; Exhalation; Failure; Flushing; Gases; Goals; Heart failure; Hypercapnia; Hypocapnia; Investigation; Israel; Kidney Failure; Legal patent; Life; Masks; Mediating; Medical; Medical center; Methods; Mixed Sleep Apnea; Modeling; Obstructive Sleep Apnea; Patients; Pattern; Phase; Phenotype; Physicians; Physiological; Polysomnography; Population; Prevention; Probability; Research; Resistance; Rights; Simulate; Sleep; Sleep Apnea Syndromes; Syndrome; System; Techniques; Technology; Testing; Titrations; Toxicity Tests; Variant; Work; adverse outcome; clinical efficacy; commercialization; cost; design; efficacy testing; improved; novel strategies; patient population; post stroke; pressure; prevent; programs; prototype; research clinical testing; research in practice; sensor; success

DESCRIPTION (provided by applicant): Although obstructive sleep apnea has received the lion's share of recognition and investigation in research and practice, more troubling forms of sleep apnea, like those that are mediated by chemoreflex instability, exist and continue to have inadequate treatment. Central apneas and periodic breathing (now called the Cheyne Stokes breathing pattern) are the classic polysomnographic markers of strong chemoreflex modulation of sleep apnea. A recently described variant, "complex sleep apnea", demonstrates sustained induction of central apneas or severe periodic breathing during positive pressure titration for what seems to be obstructive disease on the diagnostic polysomnogram. The number of the affected population is large, especially when specific populations such as congestive heart failure are considered. It is estimated that complex sleep apnea alone makes up 10%-15% of the overall sleep apnea patient population or over 1.5 million patients (assuming a conservative estimate of $10 million overall sleep apnea population). In those with significant chemoreflex modulatory effects, the probability of failure of conventional positive airway pressure therapy is high. Positive airway pressure therapies tend to flush out and reduce the level of carbon dioxide (CO2); prevention of this hypocapnia state during the application of positive airway pressure therapies is an important stabilizing factor for chemoreflex-modulated sleep apnea syndromes. The Positive Airway Pressure Gas Modulator (PAPGAM), a new class of positive airway pressure device designed to prevent chemoreflex instability by carefully maintaining CO2 levels just above the CO2-dependent apneic threshold, has shown excellent acute results. Chronic effects with a modified dead space approach, called Enhanced Expiratory Rebreathing Space, have shown some success, but are less precise than directly controlling the CO2 level. This proposal will investigate the use of exhaled air to provide the CO2 that is mixed with the inlet air of the positive airway pressure device. By controlled mixing, we hope to completely eliminate the need for the high pressure tank, or at a minimum markedly increase its life. Thus, the aim is to obtain the precision of PAPGAM treatment but with reduced cost, marked improvements in ease of use, and minimized adverse outcomes from technical failures. The goals of the phase I research include: 1) building prototypes capable of diverting or pulling the exhaled air from the patient to the inlet of the positive airway pressure device; 2) determining if a passive or an active rebreathing mechanism is required; 3) determining what maximum concentrations are possible using each technique; and 4) clinically assessing the system. Successful implementation will result in a poweful new treatment for chemoreflex-modulated sleep apnea. PUBLIC HEALTH RELEVANCE: Abnormal control of breathing during sleep causes central or mixed forms of sleep apnea and is especially common in heart failure and kidney failure patients. The usual treatment for obstructive sleep apnea, a mask and air pressure device, does not work well in those with central / mixed sleep apnea. Recent research indicates that the air pressure device decreases the normal level of carbon dioxide and excellent treatment results have been achieved by increasing carbon dioxide levels back to normal levels. The proposed research will develop methods to use carbon dioxide exhaled by the patient to provide stability of breathing patterns during sleep. Success in development of this device, called the Positive Airway Pressure Rebreathing Modulator (PAPREM, to be used with air pressure treatments) will markedly improve treatment of complicated forms of sleep apnea.

描述（由申请人提供）：尽管阻塞性睡眠呼吸暂停在研究和实践中得到了大部分的认可和调查，但更多令人不安的睡眠呼吸暂停形式，如那些由化学反射不稳定介导的形式，仍然存在，并且仍然没有足够的治疗。中心性呼吸暂停和周期性呼吸（现在称为Cheyne Stokes呼吸模式）是睡眠呼吸暂停的强化学反射调节的经典多导睡眠图标志。最近描述的一种变体，“复杂睡眠呼吸暂停”，在诊断性多导睡眠图上，正压滴定时显示持续诱导中枢性呼吸暂停或严重的周期性呼吸。受影响人群的数量很大，特别是当考虑到充血性心力衰竭等特定人群时。据估计，仅复杂睡眠呼吸暂停就占整个睡眠呼吸暂停患者人数的10%-15%，或超过150万患者（假设保守估计为1000万美元的整体睡眠呼吸暂停患者）。在那些具有明显化学反射调节作用的患者中，常规气道正压治疗失败的概率很高。气道正压疗法倾向于排出并降低二氧化碳（CO2）水平；在应用气道正压治疗期间预防这种低碳酸血症状态是化学反射调节性睡眠呼吸暂停综合征的重要稳定因素。气道正压气体调节器（PAPGAM）是一种新型气道正压装置，旨在通过小心地将二氧化碳水平维持在二氧化碳依赖的呼吸暂停阈值以上来防止化学反射不稳定，已显示出良好的急性效果。一种被称为“增强呼气再呼吸空间”（Enhanced Expiratory Rebreathing space）的改良死区方法的慢性效果已经取得了一些成功，但不如直接控制二氧化碳水平精确。本提案将研究使用呼出的空气提供与气道正压装置的入口空气混合的二氧化碳。通过控制混合，我们希望完全消除对高压储罐的需要，或至少显着增加其寿命。因此，目标是获得PAPGAM治疗的精度，同时降低成本，显著改善易用性，并最大限度地减少技术故障造成的不良后果。第一阶段研究的目标包括：1)建立能够将患者呼出的空气转移或拉到气道正压装置入口的原型；2)确定是否需要被动或主动再呼吸机制；3)确定每种技术可能达到的最大浓度；4)临床评价。成功的实施将导致化学反射调节睡眠呼吸暂停强有力的新疗法。