Targeting CO2 levels in breathing training for asthma

描述（由申请人提供）： 长期以来，呼吸训练（BT）一直被认为是哮喘的一种预防性治疗方法，但很少有对照证据表明其疗效。最近，推荐了一种通气不足训练，声称通过提高基础pCO2水平来改善哮喘控制。生理学研究支持该技术的基本原理，并且一些对照试验已经证明了训练的有限益处。然而，由于这些研究都没有提供基础pCO2水平在训练过程中增加的证据，因此通气不足训练理念的核心假设仍未得到验证。基于这一基本原理和呼吸生理学证据，我们最近开发了一种基于家庭的pCO2生物反馈辅助BT，并对哮喘患者进行了试点测试。该培训的主要目标是教患者如何增加基础pCO2水平。结果表明，该程序成功地缓解了症状，改善了哮喘的控制，并降低了肺功能的昼夜变化，这是哮喘严重程度的客观指标。我们建议进行一项为期4年的研究，系统评估基于通气不足的BT作为哮喘辅助治疗的疗效。该研究是一项随机对照试验，比较了5次通气不足训练与呼吸规律性和意识训练对照干预的短期和长期益处。我们将随机分配120名哮喘患者。将通过哮喘控制的多水平标准测量测试组合评价结局，包括病理生理学测量（峰值流量变异性、呼出一氧化氮引起的气道炎症、对乙酰甲胆碱的气道高反应性、基础肺功能）、自我报告的哮喘控制和症状以及自我用药行为（支气管扩张剂使用）。还将评估对哮喘管理（皮质激素吸入器依从性、感知控制和管理有效性、感知触发因素）、总体健康状况（感知健康、压力、焦虑、抑郁）和日常生活中的心肺功能（多系统动态呼吸感应体积描记术、二氧化碳测定、呼吸监测）的影响。我们预计二氧化碳测定辅助呼吸训练对哮喘控制的实质性益处，我们还将探索通过训练作为哮喘控制变化的介导物改善哮喘管理和总体健康（感知健康、压力、焦虑和抑郁情绪）的作用，以及呼出的一氧化氮预测整个治疗期间其他哮喘控制措施的临床显著变化的潜力。本研究将探讨一种新的呼吸训练对哮喘患者的益处，这种训练加在常规药物治疗中。训练的目的是减少过度换气，这是已知的，使哮喘恶化，但尚未成功地通过先前的呼吸训练方法的目标。我们希望我们的培训能够改善哮喘控制，减少症状和药物需求，并改善患者的健康状况。 公共卫生相关性段落：研究表明，哮喘患者可能经常高血压，这使他们的症状恶化。在这个项目中，我们将测试一种呼吸训练，这种训练可以在手持设备的帮助下减少过度通气，帮助患者监测他们的呼吸。患者将参加为期四周的干预，包括五次培训课程和呼吸家庭练习，预计将改善他们的哮喘控制和健康状况。

DESCRIPTION (provided by applicant): Breathing training (BT) has long been proposed as an adjunctive treatment for asthma, but little controlled evidence is available on its efficacy. Recently, a hypoventilation training has been recommended that claims improvements in asthma control by raising basal pCO2 levels. Physiological research supports the rationale of the technique, and a number of controlled trials have demonstrated limited benefits of the training. However, because none of these studies has provided evidence for increases in basal pCO2 levels across training, the central assumption of the hypoventilation training idea remains untested. Based on this rationale and the evidence from respiratory physiology, we recently developed and pilot-tested a home-based pCO2 biofeedback assisted BT with a handheld capnometry device for asthma patients. The primary goal of this training was to teach patients how to increase their basal pCO2 levels. The results showed that this procedure was successful in relieving symptoms, improving control of asthma, and reducing diurnal variability of lung function, an objective indicator of asthma severity. We are proposing a 4-year study to systematically assess the efficacy of hypoventilation-based BT as an adjunct treatment for asthma. The study is a randomized, controlled trial comparing the short- and long-term benefits of 5 sessions of hypoventilation training compared to a control intervention of breathing regularity and awareness training. We will randomize a total of 120 asthma patients. The outcome will be evaluated by a multi-level standard measures test battery of asthma control including measures of pathophysiology (peak flow variability, airway inflammation by exhaled nitric oxide, airway hyperreactivity to methacholine, basal lung function), self- reported asthma control and symptoms, and self-medication behavior (bronchodilator use). Effects on, asthma management (corticoid inhaler adherence, perceived control and efficacy of management, perceived triggers), general well-being (perceived health, stress, anxiety, depression), and cardio-respiratory function in daily life (multi-system ambulatory respiratory inductance plethysmography, capnometry, spiromtery) will also be assessed. We expect substantial benefits of the capnometry-assisted breathing training on asthma control, We will also explore the role of improvements in asthma management and general well- being (perceived health, stress, anxious and depressed mood) through training as a mediators of change in asthma control, as well as the potential of exhaled nitric oxide to predict clinically significant change in other asthma control measures throughout therapy. This study will explore the benefits of a novel breathing training for asthma patients added to their regular medication treatment. The trainings aims at reducing hyperventilation, which is known to make asthma worse, but which has not been targeted successfully by prior breathing training methods. We expect our training to improve asthma control, reduce symptoms and medication needs, as well as improve patients' well-being. Public Health Relevance Paragraph: Research suggests that asthma patients may often hyperventilate, which makes their symptoms worse. In this project we will test a breathing training that reduces hyperventilation with the help of a hand-held device that helps patients monitor their breathing. Patients will participate in a four-week intervention with five training sessions and breathing home exercises, which is expected to improve their asthma control and well-being.