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（由申请人提供）：众所周知，未能将节奏菌株应用于气道平滑肌会导致平滑肌生物力学的变化，其特征是缩短静息长度，并且对药物收缩的敏感性提高。哮喘患者具有生理气道特征，可概括这种情况 - 增加气道张力并提高对甲基苯胺的敏感性。我们的基本假设是，哮喘是通过气道炎症引发的，但在睡眠期间潮汐力降低而持续和促进。如果是真的，那么在睡眠期间增加气道潮气波动的处理可能会扭转这些异常。一种这样的治疗方法是连续的正气道压力（CPAP），可防止末端呼气肺部的下降，并防止肺部依赖区域中气道关闭，从而使潮汐呼吸的应力在呼吸道上施加压力。与使用SHAM CPAP或无CPAP治疗的哮喘病诱导的气道收缩相比，用CPAP处理的哮喘模型中的前线模型显示出对乙酰胆碱诱导的气道收缩的敏感性显着降低。 15种哮喘患者中的人类数据表明，8-10cm H20夜间CPAP的1周与甲基苯胺浓度增加2.7倍，导致FEV1下降20％（PC20）。这项研究的目的是进行5和10 cm H20夜间CPAP的随机，假对照，多中心研究，以确认这些发现。确定在12周内效果的耐用性；评估对这种治疗的耐受性和依从性；并探索CPAP治疗是否转化为临床意义的结果。这项研究将在约翰·霍普金斯大学（Johns Hopkins University）的数据协调中心（DCC）与美国肺协会 - 雅典 - 疾病临床研究中心（ALA-ACRC）的19个中心进行。相关性（请参阅说明）：哮喘是一种常见的慢性疾病，影响2300万美国人，是最常见的童年慢性疾病。目前旨在减少炎症和气道狭窄的药物对于许多哮喘患者来说是不够的，并且对这些药物的长期安全感到担忧。如果晚上CPAP有效，它将代表一种全新的治疗哮喘的方法。 （抽象的结尾）