Fentanyl or morphine for persistent dyspnoea in COPD: a multicentre randomised crossover trial.

Opioids, mostly morphine, have been investigated and suggested as treatment in palliative care guidelines.

在姑息治疗指南中，已经对阿片类药物，主要是吗啡进行了研究，并被建议作为治疗手段。

However, in recent years multiple trials on morphine for persistent dyspnoea have shown no clinical benefit, and there are concerns regarding adverse events.

然而，近年来多项关于持续性呼吸困难使用吗啡的试验显示没有临床益处，且有关不良事件的担忧。

Transdermal fentanyl has not yet been investigated for this indication.

经皮芬太尼尚未针对这一适应症进行研究。

Methods

We performed a multicentre, crossover, double-dummy randomised controlled trial, investigating transdermal fentanyl (12 μg·h-1), morphine (10 mg per os twice daily) and placebo, during three treatment periods of 2 weeks (including a 3-day washout period).

我们开展了一项多中心、交叉、双盲随机对照试验，研究了在三个为期2周的治疗期（包括3天的洗脱期）中，经皮芬太尼（12 μg·h-1）、口服吗啡（每日两次，每次10 mg）和安慰剂的效果。

Patients with persistent dyspnoea despite optimal therapy and modified Medical Research Council dyspnoea scale score ≥3 caused by COPD, forced expiratory volume in 1 s (FEV1) <50% predicted and stable disease were included.

纳入了尽管接受最佳治疗但仍有持续性呼吸困难、由慢性阻塞性肺疾病（COPD）引起的改良版医学研究委员会呼吸困难量表评分≥3、第一秒用力呼气量（FEV1）<50%预计值且病情稳定的患者。

The primary end-point was change in mean daily dyspnoea score on a Numeric Rating Scale (NRS).

主要终点是使用数字评分量表（NRS）评估的平均每日呼吸困难评分的变化。

Secondary outcomes were change in worst daily dyspnoea (NRS), health status (Clinical COPD Questionnaire), anxiety (Hospital Anxiety and Depression Scale-Anxiety), hypercapnia (capillary blood gas), mastery (Chronic Respiratory Questionnaire-Mastery) and sleep quality (NRS).

次要结果包括最差每日呼吸困难评分（NRS）、健康状况（COPD临床问卷）、焦虑（医院焦虑抑郁量表-焦虑部分）、高碳酸血症（毛细血管血气）、自我控制能力（慢性呼吸问卷-自我控制部分）和睡眠质量（NRS）的变化。

Results

Between April 2019 and November 2024, 59 randomisations were performed in 58 participants (mean±sd 69±7 years; 54% female; FEV1 33±10% predicted); 37 participants completed the study.

在2019年4月至2024年11月期间，共有58名参与者接受了59次随机分组（平均年龄69±7岁，54%为女性，FEV1预测值为33±10%）；其中37名参与者完成了研究。

The main reasons for study discontinuation were exacerbations (n=13) and side-effects (n=7).

研究中断的主要原因包括急性加重（n=13）和副作用（n=7）。

There were no significant differences between both fentanyl and morphine compared to placebo for mean and worst dyspnoea, sleep, health status, mastery, anxiety, hypercapnia or side-effects (except for a possible difference in vomiting).

在平均和最严重的呼吸困难、睡眠、健康状况、控制感、焦虑、高碳酸血症或副作用方面，芬太尼和吗啡与安慰剂相比没有显著差异（除可能的呕吐差异外）。

Conclusions

This study demonstrated no positive effect of transdermal fentanyl nor oral morphine compared to placebo in the treatment of persistent dyspnoea in COPD.

该研究显示，与安慰剂相比，经皮芬太尼和口服吗啡在治疗COPD持续性呼吸困难方面没有积极效果。