The Effect of Inhaled Nitric Oxide on Dyspnea and Exercise Tolerance in Interstitial Lung Disease.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 主要终点
- Exercise capacity
研究概览
简要总结
Interstitial Lung Disease (ILD) is a is a lung disorder which makes breathing more difficult. During exercise, patients with ILD are not efficient breathers and this leads to serious breathing difficulties, which often causes these patients to stop exercise at low intensities. The investigators think that these patients with ILD have problems exchanging fresh gas (i.e., oxygen) into the blood stream because of poor lung blood vessel function. The investigators will test whether inhaled medications, specifically nitric oxide, can improve lung blood vessel function and decrease breathing difficulties during exercise. With this research, the investigators will understand more about breathing efficiency and lung blood vessel function in mild ILD patients, and find out whether improving lung blood vessel function helps ILD patients breathe easier and exercise longer. Understanding the reasons behind the feeling of difficult breathing may lead to more effective therapy and improved quality of life in ILD patients.
详细描述
BACKGROUND
Interstitial Lung Disease (ILD) is a respiratory disorder characterized by chronic inflammation and fibrosis of the lung parenchyma. Exertional dyspnea (perceived breathlessness) is a hallmark of ILD regardless of severity and is the primary reason for the observed exercise intolerance, typically observed in this population. Dyspnea in ILD has been shown to profoundly reduce quality of life, physical activity, and impair the ability of participants with ILD to complete day-to-day tasks. Previous work in ILD has demonstrated that exertional dyspnea is the result of increased work of breathing during exercise, and that this increased work of breathing comes from: 1) an exaggerated ventilatory response to exercise (i.e. increased minute ventilation relative to carbon dioxide production, V̇E/V̇CO2), and 2) airflow limitation (i.e. expiratory flow limitation and resulting dynamic hyperinflation). A growing body of work has focused on respiratory mechanics in ILD; however, very little has been done to understand and treat the exaggerated ventilatory response to exercise in ILD.
Several previous studies in ILD have consistently shown an elevated ventilatory response (i.e. greater V̇E/V̇CO2) during exercise. This increased V̇E/V̇CO2 in ILD appears to be secondary to increased deadspace ventilation (i.e. sections of the lung with ventilation, but no perfusion), and this increased deadspace ventilation results in a compensatory increase in total minute ventilation (i.e. increased V̇E/V̇CO2) to maintain effective alveolar ventilation and arterial blood gas homeostasis. The underlying mechanism(s) for the increased deadspace ventilation and V̇E/V̇CO2 during exercise in mild ILD is currently unclear; however, pulmonary microvascular abnormalities and hypoperfusion of pulmonary capillaries are potential pathophysiologic mechanisms. Individuals with ILD have a reduced pulmonary capillary blood volume and, in more severe ILD, present with pulmonary vascular dysfunction and are prone to developing exercise-induced pulmonary arterial hypertension. It is likely that the pulmonary vascular dysfunction, in ILD, may impair pulmonary capillary perfusion, leading to ventilation (V̇A) -perfusion (Q̇) inequality (specifically, areas of high, V̇A/Q̇, which is indicative of increased deadspace), however this has not yet been examined. Inhaled nitric oxide (NO) is commonly used to test for pulmonary vasodilatory responses in individuals with pulmonary arterial hypertension (PAH), as it increases NO bioavailability and improves pulmonary vascular function. Previous work in PAH and heart failure (HF) has shown that standard doses (20-40 parts per million (ppm)) of inhaled NO can reduce pulmonary vascular resistance and increase peak oxygen consumption (V̇O2peak). If inhaled NO can reduce vascular dysfunction and increase perfusion in ILD, this would result in a reduction in V̇E/V̇CO2 and dyspnea, and improved exercise tolerance.
STUDY PURPOSE
Purpose: To examine the effect of inhaled NO on exercise capacity (V̇O2peak), ventilation and dyspnea in ILD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ILD participants free of any significant cardiovascular, metabolic or neuromuscular disease. Specific criteria are:
- •Established physician diagnosis of ILD
- •Forced vital capacity 50-80 % predicted
- •Diffusing capacity for carbon monoxide 35-60 % predicted
- •Able to complete a 6-minute walk test
- •Participants will range from 18-85 years old.
- •There are no restrictions on pulmonary medications, however, participants will be asked to withdraw from long-acting beta agonists 48 hours prior to trials.
排除标准
- •Participants with current or previous history of myocardial infarction or angina pectoris will be excluded.
- •Participants with a lowest arterial oxygen saturation < 84% during the initial CPET (day 1) on room air will be excluded.
- •Patient receiving treatment for isosorbide mononitrate or pulmonary arterial hypertension (PAH) medications will be excluded.
研究组 & 干预措施
Nitric Oxide
Inhaled nitric oxide, which consists of breathing medical grade air (21% O2) with 40 parts per million of nitric oxide.
干预措施: Nitric Oxide (Drug)
Placebo
Inhaled placebo, which consists of breathing medical grade air (21% O2).
干预措施: Placebo (Drug)
结局指标
主要结局
Exercise capacity
时间窗: Within 20-25 minutes post-dose
Exercise capacity as determined by peak power output and oxygen uptake (V̇O2peak).
次要结局
- Perceived breathing discomfort (Modified Borg 0-10 categorical ratio scale)(Within 20-25 minutes post-dose)
- Pulmonary vascular function(Within 5 minutes post-dose)
- Ventilation(Within 20-25 minutes post-dose)