High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children

  • Review
  • Intervention

Authors


Abstract

Background

Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma.

Objectives

To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS.

Search methods

We searched the Cochrane Airways Group trials register and reference lists of articles.Date of last search: January 2003

Selection criteria

Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS.

Data collection and analysis

Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies).

Main results

31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV1 ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ) . Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS.

Authors' conclusions

For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.

摘要

背景

以高劑量及低劑量吸入式皮質類固醇作為成年及兒童氣喘患者之起始治療

吸入式皮質類固醇(ICS)是氣喘的維持治療之基本成份,其效應已充分確立。最近的回顧顯示,ICS的效益曲?相對平坦而增加ICS的劑量則增加副作用。高劑量經常被處方而目前已有使用高劑量ICS會發生顯著副作用的報告。這些議題呈現出確立ICS治療氣喘的起始劑量的需求。

目標

評估使用高劑量及低劑量ICS作為未使用ICS之氣喘患者起始治療的效益來確立ICS的最佳起始劑量。

搜尋策略

我們搜尋Cochrane Airways Group trials register及文章的參考文獻。最近一次搜尋是在2003年1月。

選擇標準

比較同一ICS之兩種不同劑量用於原先沒有使用ICS或口服皮質類固醇的成年及兒童氣喘患者之隨機對照試驗。

資料收集與分析

由兩位審查者獨立地評估試驗品質及摘錄數據,並聯繫研究的作者來確認。試驗的分析是依據下列ICS劑量作比較;逐步減量與恆定劑量ICS相比(n = 7);高劑量與中劑量相比(n = 11);高劑量與低劑量相比(n = 9);中劑量與低劑量相比(n = 11);劑量的倍數變化(所有研究)。

主要結論

本回顧包括由26項試驗結果所報導的31篇論文。比較漸減劑量與固定的中/低ICS劑量的研究並未顯示兩種治療在肺功能、症狀、救援藥物或氣喘控制有顯著的差異。在FEV1預測百分比有顯著但臨床上僅為輕微的改善(WMD 5.32,95% CI 0.65至9.99),高劑量與中劑量ICS的比較則顯示在晨間PEF的變化有未達統計意義的改善。在高劑量與低劑量ICS兩者間之治療效益並無顯著差異。相較於低劑量ICS,中劑量ICS較能在晨間PEF 1/min比基線值(WMD 11.14,95% CI 1.34至20.93)及夜間症狀(SMD −0.29,95% CI −0.53至−0.06)有顯著的進步。開始即使用中或低劑量雙倍或四倍劑量ICS並未比開始時使用基本劑量有較大的效應。有幾項研究報導高劑量ICS對氣道過度反應有較大的改善。

作者結論

需用ICS的氣喘患者在開始時使用中劑量ICS與開始時使用高劑量ICS然後再逐漸調降劑量之效能相當。與中劑量及低劑量ICS相較,開始即使用高劑量ICS所得到微幅有意義的效益並不足以因而倡導它的使用。起始時使用中劑量ICS顯然優於起始時使用低劑量ICS。高劑量ICS可能較中劑量或低劑量ICS在氣道過度反應更有效果。在穩定的氣喘患者使用雙倍或四倍劑量的ICS並無好處。

翻譯人

本摘要由中國醫藥大學附設醫院陳祖裕翻譯。

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

總結

使用吸入式皮質類固醇(ICS)治療氣喘的指引各有不同。本回顧比較ICS在治療氣喘的起始劑量。結果顯示開始時使用中劑量ICS與開始時使用高劑量然後監測症狀來減低劑量的效果相當。這些結果亦顯示開始時使用中劑量ICS比開始時使用低劑量ICS可能較為有效。開始時使用雙倍或四倍劑量的ICS並無額外效益。氣喘患者開始接受治療時應使用低劑量至中劑量的ICS。

Plain language summary

High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children

Guidelines vary in their recommendations for the initial dose of inhaled corticosteroid (ICS) for asthma. This review compared initial ICS doses for asthma . The results showed that commencing with a moderate dose ICS is as effective as commencing with a high dose ICS and then reducing the dose whilst monitoring symptoms. These results also show that initial moderate dose ICS maybe more effective than initial low dose ICS. No extra benefit was gained by doubling or quadrupling the starting ICS dose. People with asthma should start their treatment with low to moderate doses of ICS.

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