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

气道正压通气对降低重症患者气道反应性的影响*

• 批准号: 8526520
• 负责人: Michael Frank Busk
• 金额: $ 188.71万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8526520
• 关键词: Acetylcholine; Address; Adherence; Affect; Agonist; American; American Lung Association; Animal Model; Animals; Asthma; Biomechanics; Breathing; Bronchoconstriction; Caliber; Characteristics; Childhood; Chronic Disease; Clinical Research; Continuous Positive Airway Pressure; Data; Data Coordinating Center; Defect; Disease; Failure; Fall prevention; Human; In Vitro; Inflammation; Inflammatory; Instruction; Lead; Length; Literature; Lung; Mechanics; Modeling; Multicenter Studies; Non obese; Oryctolagus cuniculus; Outcome; Participant; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Physiological; Physiology; Prevention; Principal Investigator; Property; Pulmonary Function Test/Forced Expiratory Volume 1; Randomized; Rest; Safety; Severities; Sleep; Smooth Muscle; Stress; Stretching; Subgroup; Symptoms; Testing; Translating; Universities; Wit; abstracting; airway hyperresponsiveness; airway inflammation; arm; base; clinically relevant; constriction; design; falls; human data; improved; in vivo; lung volume; methacholine; novel strategies; pre-clinical; pressure; prevent; respiratory smooth muscle

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)

描述（由申请方提供）：已明确，未能对气道平滑肌施加节律性应变会导致平滑肌生物力学变化，其特征为静息长度缩短和对药理学收缩剂的敏感性增加。哮喘患者的气道生理特征概括了这种情况-气道张力增加和对乙酰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发的，但在睡眠期间，由于潮气力波动减少而持续和促进。如果这是真的，那么在睡眠期间增加气道潮汐力波动的治疗可以逆转这些异常。一种这样的建议的治疗是持续气道正压通气（CPAP），其防止呼气末肺容量的下降并且防止肺的依赖区域中的气道闭合，从而允许潮式呼吸的应力向气道施加应变。在用CPAP治疗的哮喘兔模型中的临床前数据显示，与用假CPAP或无CPAP治疗的那些相比，对乙酰胆碱诱导的气道收缩的敏感性显著降低。15名哮喘患者的人体数据显示，8- 10 cm H20夜间CPAP治疗1周后，乙酰甲胆碱浓度增加2.7倍，导致FEV 1（PC 20）下降20%。本研究的目的是对5 cm H20和10 cm H20夜间CPAP进行一项随机、假对照、多中心研究，以证实这些发现;确定12周内效果的持久性;评估该治疗的耐受性和依从性;并探索CPAP治疗是否转化为有临床意义的结局。本研究将在美国肺脏协会-哮喘临床研究中心（ALA-ACRC）的19个中心进行，数据协调中心（DCC）位于约翰霍普金斯大学。相关性（参见说明）：哮喘是一种常见的慢性疾病，影响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是不够的，人们对这些药物的长期安全性表示担忧。如果夜间CPAP有效，它将代表一种治疗哮喘的全新方法。(End摘要）