Fluticasone at different doses for chronic asthma in adults and children

 

Abstract

Background

Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma.

Objectives

1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma.
2. To test for the presence of a dose-response effect.

Search methods

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

Selection criteria

Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality.

Data collection and analysis

One review author extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using Review Manager.

Main results

Fifty-one published and unpublished trials (representing 55 group comparisons, 10,797 participants) met the inclusion criteria. In asthmatics with mild to moderate disease who were not on oral steroids, FP did not exhibit a dose-response effect in the lower dose comparisons in FEV1 (50mcg, 100mcg, 200mcg and 4-500mcg daily). There were no statistically significant differences between 4-500mcg and 800-1000mcg, and between 50-100 and 800-1000mcg of FP. When 200mcg was compared with 800-1000mcg daily FEV1 favoured the four/five fold increase. For PEF, a dose response was present with FP when low and moderate, and low and high doses of FP were compared. There was no evidence of a dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 µg/day). People with oral steroid-dependent asthma treated with FP (2000 µg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 µg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 µg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day).

Authors' conclusions

We have not found evidence of a pronounced dose response in FEV1 with increasing doses of fluticasone. The number of studies contributing to our primary outcomes was low. At dose ratios of 1:2, there are statistically significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 µg/day) as they do on high doses (800 to 1000 µg/day). More work in severe asthma would help to confirm that doses of FP above 500 µg/day confer greater benefit in this subgroup than doses of around 200 µg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 µg/day.

 

Plain language summary

Fluticasone at different doses for chronic asthma in adults and children

Fluticasone (FP) is an inhaled corticosteroid commonly used to treat inflammation of the airways (passages to the lungs) and improve breathing in people with asthma. This review examined the effectiveness of FP when given at different doses for treating asthma in children and adults. High doses (800 to 1000 microgram per day) led to small improvements in measures of airway opening compared to low doses (50 to 100 microgram per day) in people with mild to moderate asthma. High dose FP did not lead to clear improvements in symptoms over the lower dose and increased the risk of a hoarse voice and fungal mouth infections. In people with severe asthma, very high doses FP (2000 microgram per day) appeared to allow more people on oral steroids to stop or reduce their dose of oral steroid tablets compared to lower doses of FP (1000 to 1500 microgram per day).

 

摘要

背景

使用不同劑量之Fluticasone來治療成人及兒童的慢性氣喘

吸入式fluticasone propionate(FP)是一種用於治療氣喘強效的吸入式類固醇

目標

1. 評估不同日常劑量的吸入式fluticasone在治療慢性氣喘的效益和安全性 2. 測試劑量反應效應

搜尋策略

我們搜尋Cochrane Airways Groups Trials Register(2008年1月)

選擇標準

比較以不同劑量fluticasone治療兒童或成人慢性氣喘之隨機試驗。兩位審查者獨立地評估文章是否納入及其方法與品質。

資料收集與分析

一位審查者摘取數據，另一位審查者則作檢討及確認，量性分析使用Review Manager。

主要結論

主要結論 已刊載及尚未刊載的試驗有51項(代表55個接受比較的組別，參與者共10,797人)。較低劑量的FP(50mcg, 100mcg, 200mcg及4 – 500mcg)在沒有口服類固醇之輕至中度氣喘患者，在FEV1的測量比較下，並未呈現劑量─反應效應。PF 4 – 500mcg與800 – 1000mcg及50 – 100與800 – 1000mcg之間並無統計學上顯著差異。當每日200mcg與800 – 1000mcg的FP作比較時，在FEV，呈現4/5倍的增加。當低與中及低與高劑量做比較時，PEF呈現劑量─反應效應。目前沒有證據顯示在症狀及2促效劑有劑量─反應效應。聲音沙啞及口腔白色唸珠…在使用較高劑量(500至1000mcg/d)者顯著較高的發生機率。依賴口服類固醇之氣喘患者接受FP2000g/d較接受1000至1500g/d之患者能更顯著地減低口服prednisolone測量(Peto勝算比2.8, 95% CI 1.3至6.3)。最高劑量較使用1000 – 1500g/d亦會顯著降低每日口服prednisolone之劑量(WMD 2.5g/d, 95% CI 0.1至4.0g/d)。

作者結論

作者結論 我們沒有找到證據增加fluticasone在FEV1有顯著的劑量─反應效應。能對我們初步結果有貢獻的研究不多。在低劑量範圍中，劑量比例為1：2之比較，使用較高劑量者在清晨頂?流量呈現較佳且統計學上有意義的差異，這些差異引致的臨床上的衝擊仍有待解讀。中度氣喘患者接受中劑量fluticasone(400至500 mcg/d)與接受高劑量者(800 – 1000mcg/d)所獲得氣喘控制的程度相似。對重度氣喘患者需有更多的研究來確認，對於此一氣喘族群能提供較大的效益。依賴口服類固醇的氣喘病人使用FP 2000g/d可減少其對prednisolone的需求量。

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

Fluticasone propionate(FP)是一種常用於治療呼吸道發炎的吸入式皮質類固醇，並可改善氣喘病人的呼吸狀況。本回顧檢視以不同劑量的FP治療兒童及成人氣喘患者的效果。與低劑量(50至100mcg/d)相比，較至中度氣喘患者接受高劑量(800至1000mcg/d)較能稍微改善氣道暢通的情況。在症狀改善方面，高劑量FP並未明確地優於較低劑量者，且增加聲音沙啞及口部黴菌感染的風險。非常高劑量(2000mcg/d)的FP與較低劑量FP(1000至1500mcg/d)相比，可讓較多的嚴重氣喘患者停用或減少口服類固醇的劑量。