Long-acting beta2-agonists for poorly reversible chronic obstructive pulmonary disease

 

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is characterised by partially reversible airflow limitation. Many patients have little reversibility to short acting bronchodilators, but long acting bronchodilators are frequently advocated.

Objectives

To determine the effectiveness of long acting beta-2 adrenoceptor agonists (LABAs) in COPD patients demonstrating poor reversibility to short-acting bronchodilators.

Search methods

The Cochrane Airways Group Specialised Register was searched ('all years' to 2005) along with the reference lists from identified randomised controlled trials (RCTs).

Selection criteria

All RCTs comparing inhaled LABAs (salmeterol or formoterol) with placebo in the treatment of patients with stable, poorly reversible COPD. Studies were a minimum of four weeks in duration.

Data collection and analysis

Two authors independently performed data extraction and study quality assessment. If we required additional data, we contacted authors and pharmaceutical companies sponsoring the identified RCTs.

Main results

Twenty-three published and unpublished studies (6061 participants) were included in the review. There was a significant change in forced expiratory volume in 1 second (FEV1) in favour of salmeterol 50 mcg twice daily (BID) of 51 mls (95% confidence intervals (CI) 32 to 70), end of study morning peak expiratory flow (PEF) 14.89 L/min (95% CI 10.86 to 18.91). Supplemental short-acting bronchodilator usage was reduced by just under one puff per day. There were significant differences in the total, activity and impact domain scores of the St George's respiratory questionnaire in favour of salmeterol 50 mcg BID. Findings from other health status measurements and symptom scores were conflicting. There was no significant difference in exercise tolerance. The number of participants experiencing exacerbations was significantly reduced with salmeterol 50 mcg treatment compared with placebo (numbers needed to treat to benefit 24).

Authors' conclusions

This review shows that the treatment of patients with COPD with salmeterol 50 mcg produces modest increases in lung function. There were varying effects for other important outcomes such as health related quality of life or reduction in symptoms. However, there was a consistent reduction in exacerbations which may help people with COPD who suffer frequent deterioration of symptoms prompting healthcare utilisation. The strength of evidence for the use of salmeterol 100 mcg, formoterol 12 mcg, 18 mcg, 24 mcg was insufficient to provide clear indications for practice.

 

Plain language summary

Long-acting beta2-agonists for poorly reversible chronic obstructive pulmonary disease

This review aims to determine the effectiveness of long-acting beta-agonists, salmeterol or formoterol, in the treatment of COPD (emphysema/chronic bronchitis). These drugs improve airflow in the lungs, and enable people with COPD to get on with their daily activities. Twenty-four studies (6061 participants) reported the effects of LABAs in people with COPD. People taking salmeterol 50 mcg daily do have fewer exacerbations than those on placebo, and some improvement in lung function and certain quality of life scores. The findings were not consistent enough to support a general recommendation for the use of these drugs in the group of people with COPD with minimal variation in their lung function, although there is some evidence of improvement in important outcomes and these findings require further exploration in additional trials.

 

摘要

背景

長效BETA2作用劑對低可逆性慢性阻塞性肺病的效用

慢性阻塞性肺病(COPD)的特點是部分可逆的受限呼吸氣流。許多病人不太愛用短效型支氣管擴張劑，但卻喜歡使用長效型的支氣管擴張劑。

目標

要確定長效BETA2腎上腺素接受作用劑(LABAs)在認為對於短效型支氣管擴張劑低可逆性的COPD患者的效用。

搜尋策略

搜尋了The Cochrane Airways Group Specialised Register (直到2005年的所有年份) 以及從確定的隨機對照試驗(RCTs)得來的參考名單。

選擇標準

所有RCTs比較吸入LABAs(salmeterol或formoterol)及安慰劑對於穩定及較差可逆性COPD患者的治療。研究至少有四個星期的時間。

資料收集與分析

兩位作者獨立的進行數據分析和研究品質的評估。如果我們需要更多的數據，我們會接觸作者和贊助被確認的RCTs的製藥公司。

主要結論

23個已發表和未發表的研究報告(包含了6061個受試者)被列入了評估。在1秒鍾出力呼氣量(FEV1)有一個重大變化達到51毫升，當每日2次使用 salmeterol 50微克(BID)(95％信賴區間(CI)32至70)，研究結束時的早上呼氣流量尖峰值(PEF)14.89升/分(95％CI為10.86至18.91)。支持性短效支氣管擴張劑的使用量每天只減少了將近一次的吸入量。對於使用salmeterol 50微克(BID)的St. George呼吸問卷中整體、活動和影響領域分數有顯著性差異。從其他健康狀況的測量和症狀評分所得的結果是矛盾的。運動耐力上無顯著差異。受試者中經歷病情加重情況的數字明顯減少當比較治療時使用salmeterol 50微克與安慰劑。(達到有益的統計數為24)。

作者結論

這項審查表明，使用salmeterol50微克治療COPD患者可以適度的增加肺功能。對其他重要的成果有不同的影響，如健康相關的生活品質或減輕症狀。然而，對緩和病情加重的狀況有一個一致的結果並可能幫助經常性症狀惡化而需就醫的COPD患者。證據的強度對於使用100微克的salmeterol， 12微克、18微克及24微克的formoterol案例，不足以提供給診療明確的指示。

翻譯人

本摘要由臺北醫學大學萬芳醫院劉怡敏翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

本次審查的目的是確定長效BETA2作用劑，salmeterol或formoterol，在治療COPD(肺氣腫 /慢性支氣管炎)的效用。這些藥物改善在肺部的氣流，並使COPD患者能從事日常活動。24個研究(包含6061個受試者)報告LABAs對COPD患者的影響。每天使用50微克salmeterol的確有較少出現病情加重的情況相對於服用安慰劑而言，並且改善肺功能和生活品質分數。相關研究的結果並不一致，且不足以支持對COPD病患建議使用這些藥物且對他們的肺功能只有最小的變化，雖然有一些證據顯示改善的重要成果，但是這些研究結果需要對其他研究做進一步探索。