Intervention Review

Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children

  1. Muireann Ni Chroinin1,*,
  2. Toby J Lasserson2,
  3. Ilana Greenstone3,
  4. Francine M Ducharme4

Editorial Group: Cochrane Airways Group

Published Online: 17 FEB 2010

Assessed as up-to-date: 8 DEC 2008

DOI: 10.1002/14651858.CD007949

Database Title

Additional Information

How to Cite

Ni Chroinin M, Lasserson TJ, Greenstone I, Ducharme FM. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD007949. DOI: 10.1002/14651858.CD007949.

Author Information

  1. 1

    Cork University Hospital, Division of Children's Services, Cork, Ireland

  2. 2

    St George's, University of London, Community Health Sciences, London, UK

  3. 3

    Montreal Children's Hospital, Montreal, Canada

  4. 4

    University of Montreal, Research Centre, CHU Sainte-Justine and the Department of Pediatrics, Montreal, Québec, Canada

*Muireann Ni Chroinin, Division of Children's Services, Cork University Hospital, Cork, Ireland. Muireann.NiChroinin@hse.ie.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 FEB 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Long-acting ß2- agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children.

Objectives

To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma.

Search methods

We searched the Cochrane Airways Group Asthma Trials Register (May 2008).

Selection criteria

We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals.

Data collection and analysis

Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible.

Main results

A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS:

(1) The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV1 at baseline was 80% of predicted or above in 10 studies; FEV1 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1 with the addition of LABA (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant group differences in symptom-free days, hospital admission, quality of life, use of reliever medication, and adverse events. Withdrawals occurred significantly less frequently with the addition of LABA.

(2) A total of seven studies assessed the addition of LABA to ICS therapy compared with an increased dose of ICS randomising 1021 children. The mean age of participants was 8 years with 67% of males. The baseline mean FEV1 was 80% of predicted or above in 2 of the 3 studies reporting this characteristic. All trials enrolled participants who were inadequately controlled on a baseline dose equivalent to 400 mcg/day of beclomethasone or less. There was no group significant difference in the risk of an exacerbation requiring oral steroids with the combination of LABA and ICS compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The increased risk of hospital admission with combination therapy was also not statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose ICS, use of LABA was associated with a significantly greater improvement in morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were insufficient data to aggregate data on FEV1, symptoms, rescue reliever use, and quality of life. There was no statistically significant difference in the overall risk of all cause withdrawals (five studies; RR 0.71; 95% CI 0.42 to 1.20. There was no group difference in the risk of overall adverse effects detected. Short term growth was significantly greater in children treated with combination therapy compared to double dose ICS (two studies: MD 1.2 cm/year; 95% CI 0.72 to 1.7).

Authors' conclusions

In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but was superior for improving lung function compared to the same dose of ICS. Similarly, compared to a double dose ICS, the combination of LABA and ICS did not significantly increase the risk of exacerbations requiring oral steroids, but was associated with a significantly greater improvement in PEF and growth. The possibility of an increased risk of rescue oral steroids and hospital admission with LABA therapy needs to be further examined.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children

Most consensus statements recommend the use of long-acting ß2-agonists (LABA) as adjunct therapy to inhaled corticosteroids for poorly controlled asthma. The purpose of this review was to identify the benefits and safety profile of adding long-acting ß2-agonists to inhaled corticosteroids in asthmatic children. Based on the identified paediatric randomised trials, the addition of long-acting ß2-agonists did not significantly reduce the risk of asthma exacerbations requiring rescue systemic steroids, but improved lung function compared to ongoing treatment with a similar dose of inhaled corticosteroids. There was no evidence of increased serious side effects or withdrawals with the addition of long-acting ß2-agonists. Compared to doubling the dose of inhaled corticosteroids, the combination of LABA and inhaled steroids did not lead to a significant reduction in the rate of moderate exacerbations or hospital admissions, but it improved lung function and lead to greater growth.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

添加長效型支氣管擴張劑(longacting betaagonists)至吸入型類固醇(inhaled corticosteroids)中對於治療幼童慢性氣喘的效果

將長效型支氣管擴張劑(longacting betaagonists， LABA)和吸入型類固醇(inhaled corticosteroids，ICS)合併使用的治療方式越來越常見於氣喘幼童的治療處方中。

目標

比較添加LABA至ICS中(ICS使用同劑量或較高劑量)對於幼童氣喘治療的安全性及效益。

搜尋策略

我們檢索了Cochrane Airways Group Asthma Trials Register資料庫(2008年5月)。

選擇標準

納入針對合併使用LABA和ICS和單獨使用同劑量或較高劑量ICS，對於幼童或青少年氣喘治療進行比較的隨機對照試驗，主要結果定義為症狀惡化到需要使用口服類固醇的比率，次要結果包括肺功能、症狀、不良事件和停藥等。

資料收集與分析

研究會由2位審閱作者分別針對方法學品質和萃取出的數據進行評估，在可能的狀況下會由試驗作者進行確認。

主要結論

本回顧納入25個試驗，其中包括31個對照介入性治療的比較結果，受試者為隨機挑選的5572位幼童。大多數的受試者在現行使用的ICS劑量下其症狀無法獲得適當的控制。我們將LABA添加至相同劑量及更高劑量的ICS中，並評估其治療功效：(1)將LABA添加至ICS中與使用同劑量ICS進行比較，在24個試驗中有16個試驗每天使用400微克以下的beclomethasone，受試者的平均年齡為10歲，受試者中有64％為女性族群，在10個試驗中基準值上平均的FEV1值為預期的80％以上，在8個試驗中，FEV1值為預估值的61至79％，而剩下的試驗沒有這樣數值的報告，除了7個試驗之外，所有的試驗在進行隨機化分配之前患者的氣喘症狀都沒有獲得適當的控制，相對於單獨使用ICS來說，添加LABA至ICS中與症狀惡化至需要使用口服類固醇的機率明顯降低無關(7個試驗的RR值為0.92，95％的CI 介於0.60至1.40之間)。相對於單獨使用ICS來說，添加LABA可以明顯改善FEV1值(9個試驗，0.08公升，95％的CI 介於0.06至0.11之間)，但是對於沒有症狀發作天數、住院率、生活品質、使用舒緩藥劑等數據來說，在各組別之間沒有統計學上的明顯差異，添加LABA也可以明顯降低停藥頻率。(2)針對7個試驗隨機選取的1021位幼童，比較添加LABA至ICS中和增加ICS使用劑量的效果，受試者的平均年齡為8歲，其中有67％為女性，3個試驗中有2個試驗報告基準的平均FEV1值為預期的80％以上，所有納入試驗的受試者在接受相當於每天400微克beclomethasone以下的基本劑量治療時，症狀都無法或的適當的控制，在比較使用LABA和ICS的混合藥劑和2倍劑量ICS藥劑的功效時，在症狀惡化至需要使用口服類固醇的風險數據上兩組之間並沒有出現顯著差異(2個試驗，RR值為1.5，95％的CI 介於0.65至3.48之間)，因為使用混合藥物治療而造成住院率增加的風險也沒有統計學上的顯著差異(RR值為2.21，95％的CI 介於0.74至6.64之間)，相對於使用雙倍ICS劑量來說，使用混合式藥劑與早晨PEF值(4個試驗，MD值為每分鐘7.55公升，95％的CI 介於3.57至11.53之間)和傍晚PEF值(3個試驗，MD值為每分鐘5.5公升，95％的CI 介於1.21至9.79之間)的明顯改善有關，但是缺乏有效的數據來總計說明FEV1、症狀、使用緊急舒緩劑和生活品質的變化，全原因停藥的整體風險值上，各組之間也沒有出現顯著差異(5個試驗，RR值為0.71，95％的CI 介於0.42至1.20之間)，對於整體不良事件發生風險上並沒有偵測到組別之間的差異，使用混合藥劑治療的幼童會比使用倍ICS劑量治療的幼童在短期成長的數值上有更明顯的增加(2個試驗，MD值為每年1.2公分，95％的CI 介於0.72至1.7之間)。

作者結論

對於患有持續性氣喘的幼童來說，將LABA添加至ICS中與症狀惡化至需要使用全身性類固醇的機率明顯降低無關，但是相對於使用相同劑量的ICS來說，卻能使肺部功能有明顯的改善，相同的，與使用雙倍ICS劑量相較，將LABA和ICS混合使用並不會明顯增加因症狀惡化而需要使用口服式類固醇的風險，但是卻與PEF值和生長狀況有明顯的改善有關，使用LABA治療是否會增加使用緊急口服式類固醇和住院的風險仍需要進一步進行評估。

翻譯人

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

總結

大多數的共識聲明都會建議將LABA當作ICS的附加治療藥劑來控制氣喘症狀，本研究想要確認將LABA添加至ICS中對於氣喘幼童進行治療的安全性及有效性。針對幼童進行的隨機試驗來看，相對於正在使用相同劑量ICS的組別來說，添加LABA並不會明顯降低因為症狀惡化而需要緊急使用全身性類固醇的風險，但是可以改善肺部功能。目前也沒有證據可以證明嚴重副作用和停藥機率的增加是因為添加LABA所致，相對於使用雙倍劑量ICS的組別來說，將LABA和ICS混合使用並不會明顯降低中度症狀惡化比例或是住院率，但是可以改善肺部功能和提升生長速率。

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