Liu-Shiu-Cheong Patrick S K, Lipworth Brian J, Weir-McCall Jonathan R, Houston J Graeme, Struthers Allan D
Division of Molecular and Clinical Medicine, University of Dundee, Dundee DD1 9SY, UK.
Department of Respiratory Medicine, Victoria Hospital, NHS Fife, Kirkcaldy KY2 5AH, UK.
Int J Chron Obstruct Pulmon Dis. 2020 Aug 25;15:2015-2024. doi: 10.2147/COPD.S260917. eCollection 2020.
Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD).
We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT).
Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV 60% and resting SpO 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI -4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation.
Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.
氧化应激（OS）与肺动脉高压（PH）及心室肥厚的发生有关。黄嘌呤氧化酶是公认的活性氧来源，可导致氧化应激。本概念验证研究的目的是评估别嘌醇（黄嘌呤氧化酶抑制剂）是否能减轻与慢性肺病相关的肺动脉高压（PH-CLD）患者的右心室质量（RVM）。
我们对PH-CLD患者（93%为慢性阻塞性肺疾病，7%为特发性肺纤维化）进行了一项随机、双盲、平行组、安慰剂对照试验，这些患者被随机分配接受别嘌醇或安慰剂治疗12个月。主要结局是通过心脏磁共振成像（CMRI）评估的RVM平均变化。次要结局包括生活质量（QOL）、肺功能测定和六分钟步行试验（6MWT）。
共招募了71名患者：平均年龄71岁，平均肺动脉压30mmHg，第1秒用力呼气容积占预计值百分比为60%，静息时血氧饱和度为96%。12个月后，RVM相对于基线的变化无显著差异（别嘌醇组为1.85g，安慰剂组为0.97g，平均差异为0.88g，可信区间为-4.77至3.01，p=0.7）。MRI测量的其他心脏参数、QOL、肺功能测定和6MWT也无显著变化。亚组分析显示，在气流受限更严重的慢性阻塞性肺疾病患者中，与安慰剂相比，别嘌醇显著降低了RVM，分别为-6.16g和0.75g，平均差异为6.92g（可信区间为1.14至12.69，p=0.02）。
别嘌醇对PH-CLD患者总体无影响，但对气流受限更严重的慢性阻塞性肺疾病患者可能有益。
