Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients wit*

描述（由申请人提供）：已经确定的是，未能对气道平滑肌施加有节奏的张力会导致平滑肌的生物力学变化，其特征是静息长度缩短，对药物收缩剂的敏感性增加。哮喘患者的生理性气道特征概括了这种情况-气道张力增加和对甲胆碱的敏感性增加。我们的基本假设是，哮喘是由气道炎症引起的，但在睡眠期间潮汐力波动的减少会持续和促进哮喘。如果这是真的，那么增加睡眠期间气道潮汐力波动的治疗可以逆转这些异常。其中一种建议的治疗方法是持续气道正压通气（CPAP），它可以防止呼气末肺容量下降，防止肺依赖区域的气道关闭，从而允许潮汐呼吸的压力对气道施加压力。临床前数据显示，与假CPAP或无CPAP治疗相比，CPAP治疗的哮喘兔模型对乙酰胆碱诱导的气道收缩的敏感性显著降低。15例哮喘患者的人体数据显示，1周8-10cm H20夜间CPAP与甲胆碱浓度增加2.7倍相关，导致FEV1 （PC20）下降20%。本研究的目的是进行一项随机、假对照、多中心的5和10 cm H20夜间CPAP研究，以证实这些发现；在12周内确定效果的持久性；评估这种治疗的耐受性和依从性；并探讨CPAP治疗是否转化为有临床意义的结果。该研究将在美国肺脏协会-哮喘临床研究中心（ALA-ACRC）的19个中心与约翰霍普金斯大学的数据协调中心（DCC）进行。相关性（见说明）：哮喘是一种常见的慢性疾病，影响着2300万美国人，是儿童最常见的慢性疾病。目前旨在减少炎症和气道狭窄的药物对许多哮喘患者来说并不足够，而且人们对这些药物的长期安全性提出了担忧。如果夜间CPAP有效，它将代表一种治疗哮喘的全新方法。（摘要结束）

DESCRIPTION (provided by applicant): It is well established that failure to apply rhythmic strain to airway smooth muscle leads to a change in the biomechanics of the smooth muscle characterized by shortened resting length, and increased sensitivity to pharmacologic constrictors. Patients with asthma have physiologic airway characteristics that recapitulate this condition - increased airway tone and increased sensitivity to methacholine. It is our underlying hypothesis that asthma is initiated by airway inflammation, but is sustained and promoted by decreased tidal force fluctuations during sleep. If true, then treatments that increase tidal force fluctuations of airways during sleep could reverse these abnormalities. One such proposed treatment is continuous positive airway pressure (CPAP) which prevents the fall in end expiratory lung volume and prevents closure of airways in dependent regions of the lung ~ thereby permitting the stresses of tidal breathing to apply strain to the airways. Preclinical data in rabbit models of asthma treated with CPAP showed significantly reduced sensitivity to acetylcholine-induced airway constriction compared to those treated with sham CPAP or no CPAP. Human data in 15 asthmatics showed that 1 week of 8-10cm H20 nocturnal CPAP was associated with a 2.7-fold increase in the concentration of methacholine causing a 20% fall in FEV1 (PC20). The objective of this study is to conduct a randomized, sham-controlled, multicenter study of 5 and 10 cm H20 nocturnal CPAP in order to confirm these findings; to determine the durability of the effect over 12 weeks; to assess the tolerability and adherence to this treatment; and to explore if CPAP treatment translates into clinically meaningful outcomes. The study will be conducted at 19 centers of the American Lung Association-Asthma Clinical Research Centers (ALA-ACRC) with a data coordinating center (DCC) at Johns Hopkins University. RELEVANCE (See instructions): Asthma is a common chronic disease that affects 23 million Americans and is the most common chronic disease of childhood. Current drugs, aimed at reducing inflammation and airway narrowing are not adequate for many asthma sufferers, and concerns have been raised about long-term safety of these drugs. If CPAP at night is effective, it will represent an entirely new approach to treating asthma. (End of Abstract)