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乙酰唑胺对慢性阻塞性肺疾病患者前往高原时肺血管血流动力学的影响:一项随机、安慰剂对照、双盲试验。

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial.

作者信息

Lichtblau Mona, Saxer Stéphanie, Mayer Laura, Sheraliev Ulan, Mademilov Maamed, Furian Michael, Buergin Aline, Schweiwiller Philipp M, Schneider Simon R, Tanner Felix C, Sooronbaev Talant, Bloch Konrad E, Ulrich Silvia

机构信息

Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Swiss-Kyrgyz High Altitude Medicine and Research Initiative, Zurich, Switzerland, and Bishkek, Kyrgyz Republic.

出版信息

ERJ Open Res. 2023 Apr 11;9(2). doi: 10.1183/23120541.00412-2022. eCollection 2023 Mar.

Abstract

BACKGROUND

COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP).

METHODS

In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2-3 who were living <800 m and had peripheral oxygen saturation ( ) >92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125-250 mg·day) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG).

RESULTS

112 patients (68% men, mean±sd age 59±8 years, forced expiratory volume in 1 s (FEV) 61±12% pred, 95±2%) were included. Mean±sd TRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of -5 (-9 to -1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sd was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001).

CONCLUSIONS

In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation.

摘要

背景

慢性阻塞性肺疾病(COPD)可能使患者在高海拔地区易出现症状性肺动脉高压。我们研究了患有COPD的平原居民上升到3100米时的血流动力学变化,并评估预防性使用乙酰唑胺治疗是否会减弱海拔引起的肺动脉压(PAP)升高。

方法

在这项随机、安慰剂对照、双盲、平行组试验中,将慢性阻塞性肺疾病全球倡议组织(GOLD)2 - 3级、居住在海拔<800米、外周血氧饱和度( )>92%且动脉血二氧化碳分压<6 kPa的COPD患者随机分为两组,从海拔760米开始上升前24小时及在3100米停留2天期间,分别接受乙酰唑胺(125 - 250毫克·天)或安慰剂胶囊治疗。在海拔760米处及在3100米度过第一个夜晚后进行超声心动图、脉搏血氧饱和度测定和临床评估。主要结局是通过三尖瓣反流压力梯度(TRPG)评估的PAP。

结果

纳入112例患者(68%为男性,平均±标准差年龄59±8岁,第1秒用力呼气容积(FEV)为预计值的61±12%, 95±2%)。分配到安慰剂组的54例患者中,平均±标准差TRPG从22±7 mmHg增至30±10 mmHg,分配到乙酰唑胺组的58例患者中,从20±5 mmHg增至24±7 mmHg(均p<0.05),平均(95%CI)治疗效果为 -5(-9至 -1)mmHg(p = 0.015)。在海拔760米/3100米处分配到安慰剂组的患者中,平均±标准差 为95±2%/88±3%;在乙酰唑胺组中,相应值分别为94±2%/90±3%(均p<0.05),治疗效果为 +2(1至3)%(p = 0.001)。

结论

对于前往3100米的患有COPD的平原居民,预防性使用乙酰唑胺治疗可减弱海拔引起的PAP升高并改善氧合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/897b/10086691/f33c67a392f5/00412-2022.01.jpg

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