Acute Effects of Aerosolized Iloprost in COPD Related Pulmonary Hypertension - A Randomized Controlled Crossover Trial

BackgroundInhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).
ObjectivesTo evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.
MethodsA randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.
ResultsBoth iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means −1.0%, p = 0.035) as well as high dose iloprost (−2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (−76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (−3.0l/min, p<0.001).
ConclusionsImprovement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.
Trial RegistrationControlled-Trials.com ISRCTN61661881

背景：吸入用伊洛前列素（iloprost）可能改善慢性阻塞性肺疾病（COPD）合并继发性肺动脉高压（PH）患者的血流动力学与气体交换功能。
研究目的：评估雾化吸入伊洛前列素对慢性阻塞性肺疾病相关性肺动脉高压患者的急性效应。
研究方法：本研究于单家三级医疗中心开展，纳入16例经有创检查确认合并肺动脉高压的慢性阻塞性肺疾病患者，采用随机双盲交叉试验设计。所有受试者在不同的研究访视中分别接受单次剂量10微克伊洛前列素（低剂量组）、20微克伊洛前列素（高剂量组）及安慰剂干预。本研究的主要终点为通过6分钟步行距离评估的运动耐量。
研究结果：两种剂量的伊洛前列素均未改善受试者的6分钟步行距离（p=0.36）。低剂量伊洛前列素（平均差值为-1.0%，p=0.035）与高剂量伊洛前列素（平均差值为-2.2%，p<0.001）均会显著损伤静息状态下的氧合功能。三种干预方式下的峰值耗氧量与二氧化碳产生量均存在显著统计学差异（分别对应p=0.002与p=0.003）。与安慰剂组相比，低剂量伊洛前列素干预可导致峰值耗氧量降低（-76ml/min，p=0.002）、二氧化碳分压升高（0.27kPa，p=0.040）以及运动过程中通气功能受损（-3.0L/min，p<0.001）。
研究结论：对于合并轻中度肺动脉高压的慢性阻塞性肺疾病患者，吸入伊洛前列素后其运动耐量得到改善的可能性极低。
试验注册：受控试验网（Controlled-Trials.com）登记号ISRCTN61661881