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Budesonide at different doses for chronic asthma

  • Review
  • Intervention

Authors


Abstract

Background

Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma.

Objectives

To assess the efficacy and safety of budesonide at different doses in order to establish whether a clinically significant dose response profile exists.

Search methods

A search was carried out for Controlled Clinical Trials using the Cochrane Airways Group trial register.

Selection criteria

Randomised trials in children and adults comparing one dose of budesonide to a second dose in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.

Data collection and analysis

One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager 4.0.4 with MetaView 3.1.

Main results

24 studies met the inclusion for the review (3907 participants). In non-oral steroid treated, mild to moderately severe asthma, no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation was apparent when treating patients with BUD 800 mcg/d compared to 200 mcg/d: Relative Risk 3.93 (95% confidence interval, 1.4 to 10.9). This result was weighted largely by a single, large, high quality RCT. In severe asthma significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 but not morning PEFR. This finding was based on two large RCTs of good quality. In oral steroid treated asthmatics no dose dependent oral steroid sparing effect was apparent for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d was apparent but the clinical significance of these findings is unclear.

Authors' conclusions

Budesonide exhibits a significant dose response effect between low and high dose for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear.

摘要

背景

以不同劑量的Budesonide治療慢性氣喘

有一系列劑量的吸入式budesonide(BUD)可用於治療慢性氣喘

目標

評估以不同劑量的budesonide治療慢性氣喘的療效及安全性,藉以確認具有臨床意義的劑量反應輪廓(dose response profile)是否存在。

搜尋策略

在搜尋Cochrane Airways Group Trial Register搜尋對照臨床試驗。

選擇標準

本回顧納入比較兩種劑量的budesonide用以治療兒童及成人慢性氣喘的隨機試驗。兩位評論者獨立地評估文獻的納入及方法學的品質。

資料收集與分析

其中一位評論者負責摘錄數據,並聯繫作者訪查欠缺的資訊。量性分析是使用Review Manager 4.0.4及Meta View 3.1。

主要結論

有24項研究符合回顧的納入標準(3907名受試者)。在非口服類固醇治療之輕至中度氣喘,無論是FEV1、清晨PEER、症狀評分或使用貝他2型促效劑救援,在200 – 1600 mcg/日此一劑量範圍內並無臨床上有意義的差異。然而,對中至重度的氣喘,使用800 mcg/日相較於使用200 mcg/日,受試者因氣喘惡化而退出試驗的可能性則呈有意義的降低。相對風險 3.93(95%信任區間 1.4 – 10.9)。此一結果主要依據一項大型高品質的RCT。高劑量BUD(1600 mcg/日)較低劑量BUD(200 mcg/日)能顯著地改善重度的氣喘是藉由FEV1而非清晨PEER的數值顯示。此一結果是基於兩項大型高品質的RCTs。在口服類固醇治療之氣喘病患,使用1600 mcg/日、800 mcg/日及400 mcg/日之BUD並未呈現劑量相關性的類固醇助減效益。注射合成ACTH後之24小時尿液游離可體松及血清可體松,在800 – 3200 mcg/日此一劑量範圍內呈現具有統計學意義的劑量相關性抑制,但這些發現在臨床上的意義卻不清楚。

作者結論

高、低劑量budesornide的劑量相關效應可見於重度的氣喘FEV1的改善及中至重度的氣喘氣喘惡化發作的減少。在非口服類固醇治療之輕至中度氣喘,則未見FEV1、PEER或症狀呈現劑量相關的改善。以敏感方法測量下丘腦垂體腎上腺功能則見有劑量相關的變化,但這些變化在臨床上的意義卻不清楚。

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

很少證據指出增加budesonide的劑量能改善輕度且控制良好氣喘患者的症狀。然而,重度氣喘病患使用高劑量budesonide會可能獲得效益。Budesonide是一種用以治療氣喘時呼吸道發炎的吸入式類固醇。本回顧顯示不同劑量budesonide對不同程度的氣喘病患所產生的效應。使用低劑量(200 mcg/日)與高劑量(1600 mcg/日)的輕至中度氣喘病患,其在氣道開程度及症狀等方面均無重大差別。然而,與使用低劑量(200 mcg/日)相較,嚴重的氣喘病患在常規使用高劑量(1600 mcg/日)時較不會發生急性惡化。未來的研究應報導更詳盡的結果,且應使用生活品質問卷。

Plain language summary

Budesonide at different doses for asthma

Budesonide is an inhaled corticosteroid used to treat the inflammation of airways (passages to the lungs) that occurs in asthma. This review presents the effects of budesonide at different doses for people with varying degrees of asthma. In patients with mild-moderate asthma no important differences were apparent between the lowest dose (200 mcg/d) and the highest dose (1600 mcg/d) for measures of airway opening and symptoms. However, patients with more severe asthma are less likely to experience an acute worsening of their asthma control when a higher dose (1600 mcg/d) is used regularly compared to a lower dose (200 mcg/d). Future research should report results more comprehensively, and should use quality of life questionnaires.

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