The Effect of Inhaled Nitric Oxide (iNO) on Physiologic Dead Space in Patients With Mild Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Inspiratory neural drive
研究概览
简要总结
Chronic obstructive pulmonary disease (COPD) is a progressive disease of the respiratory system that generally develops as a result of smoking. Most people with COPD are classified as having "mild" disease severity and may not have significantly impaired lung function (e.g. flow) as measured by traditional lung function tests. However, multiple studies have shown that patients with mild disease already have significant damage to the small airways and blood vessels of the pulmonary system. This results in a considerable portion of the lung that does not participate in gas exchange, a phenomenon called physiologic dead space. Mild COPD patients develop symptoms of intolerable breathlessness early in exercise compared with healthy individuals. Previous studies have shown that pulmonary vasodilators, which locally increase blood vessel radius, may improve gas exchange and reduce symptoms of breathlessness in patients with mild COPD. Therefore, the objective of this study is to determine the effect of reducing dead space with a pulmonary vasodilator on the intensity of breathlessness during exercise in patients with mild COPD. This five visit, double-blinded, placebo-controlled crossover study will test the impact of inhaled nitric oxide, a direct vasodilator, during cardiopulmonary exercise on dead space and breathlessness intensity. Use of an esophageal catheter during testing will additionally permit measurement of neural drive to breathe and pulmonary mechanics throughout the protocol. Though patients with mild COPD represent the majority of the COPD population, their symptoms remain poorly managed by current, inefficient standard of care. The proposed study will examine dead space reduction as a novel therapeutic target for improving breathlessness and exercise tolerance in patients with mild COPD.
详细描述
This study will recruit 20 current or ex-smokers who meet the criteria for mild chronic obstructive pulmonary disease (COPD), measured by lung function tests. Participation is voluntary and participants may withdraw from the study at any time.
Procedures:
General Medical Examination: All participants will undergo a physical examination conducted by a physician. Concomitant medications will be recorded as well as body height and weight; blood pressure; heart rate rhythm using a 12-lead electrocardiogram (ECG); and blood oxygen saturation. The physician will identify any contraindications to exercise testing that would prevent safe participation.
Pulmonary Function Tests: Standard lung function tests include: spirometry (measuring respiratory flow during a maximal breath outward); body plethysmography (measuring lung volumes); diffusing capacity for carbon monoxide (DLCO; measuring gas exchange across the lung); maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) maneuvers (evaluating respiratory muscle strength); and impulse oscillometry (IOS; measuring lung mechanics). Each test will be performed at least 2-3 times to ensure the results are consistent. For all tests, the participant will breathe through a rubber mouthpiece with nose clips on to occlude the nasal passage.
Cardiopulmonary Exercise Tests: The participants will perform exercise on a stationary bicycle at each visit. While exercising, they will breathe through a mouthpiece with nose clips on, which allows for the breath-by-breath recording of physiologic variables throughout exercise. For each test, the participant will begin by sitting on the bike at rest (no pedaling) for approximately 6 minutes to establish a consistent measure of their baseline breathing. They will then begin pedaling for 1 minute against no resistance to warm-up. The load will then increase either by 10 Watts every minute (Visit 1) or to a constant work rate that will be maintained for 4 minutes (Visits 2-5). Every 2 minutes, the participant will be asked to take a full breath all the way in (an inspiratory capacity (IC) maneuver). The participant will also be asked to rate their breathing discomfort, their leg discomfort, how unpleasant their breathing feels, and how difficult it is to breathe in and out, using a 10-point Borg Scale.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •clinically stable as defined by stable hemodynamic status, optimized medical treatment, no changes in medication dosage or frequency of administration with no hospital admission in the preceeding 6 weeks
- •current or ex-smokers (>=20 pack-years)
- •male or female >45 years of age
- •mild COPD as defined by Medical Research Council dyspnea scale >=3 and post-bronchodilator FEV1 >=80% predicted and FEV1/FVC <0.7 and <LLN
- •ability to perform all study procedures and provide/sign informed consent
排除标准
- •women of childbearing age who are pregnant or trying to become pregnant
- •active cardiopulmonary disease or other comorbidities that could contribute to dyspnea and exercise limitation
- •important contraindications to clinical exercise testing, including inability to exercise because of neuromuscular or musculoskeletal disease(s)
- •use of daytime oxygen, or exercise-induced O2 desaturation to <80% on room air
- •body mass index (BMI) <18.5 or =>35.0 kg/m2
- •echocardiographic evidence of pulmonary hypertension
- •prior history of pulmonary thromboembolism or systemic vasculopathy
研究组 & 干预措施
Inhaled Nitric Oxide
Inhaled nitric oxide administered throughout 4 min exercise protocol at 800 ppm.
干预措施: Nitric Oxide (Drug)
Placebo
Inhaled room air administered throughout 4 min exercise protocol at FiO2 = 0.21.
干预措施: Placebo (Drug)
结局指标
主要结局
Inspiratory neural drive
时间窗: At 4 minutes from start of exercise
Primary objective is to measure inspiratory neural drive (IND) by diaphragm activation (EMGdi/EMGdi max) at isotime (maximum exercise time achieved by all participants) during cardiopulmonary exercise testing (cycle ergometer).
Dyspnea Intensity
时间窗: At 4 minutes from start of exercise
Primary objective is to measure perceptual (e.g. intensity of dyspnea and leg discomfort) responses at isotime (maximum exercise time achieved by all participants) during a standardized cardiopulmonary exercise testing (cycle ergometer).
次要结局
- Lung volumes(At 4 minutes from start of exercise)
- Trans-diaphragmatic Pressure (Pdi)(At 4 minutes from start of exercise)
- Gastric Pressure (Pga)(At 4 minutes from start of exercise)
- Metabolic and gas exchange(At 4 minutes from start of exercise)
- Esophageal Pressure (Pes)(At 4 minutes from start of exercise)
研究者
Dr. Denis O'Donnell
Principal Investigator
Queen's University