徐 飛,崔文強,吳 曉,董競成
?
·專題研究·
布地奈德與全身性激素治療COPD急性加重期療效的Meta分析
徐 飛,崔文強,吳 曉,董競成
目的 通過系統(tǒng)評價的方法,比較布地奈德(BUD)與全身性激素(SCS)治療COPD急性加重期(AECOPD)的有效性與安全性。方法 計算機檢索PubMed、Web of Science、中國知網(wǎng)、維普網(wǎng)、中國生物醫(yī)學(xué)文獻數(shù)據(jù)庫(CBM)中關(guān)于BUD(試驗組)與SCS(對照組)治療AECOPD的文獻,檢索時間均從建庫至2014年7月。提取肺功能、動脈血氣分析、呼吸困難評分、COPD 評估測試(CAT)問卷評分、不良反應(yīng)資料。結(jié)果 納入19篇符合標(biāo)準(zhǔn)的文獻。Meta分析結(jié)果顯示,兩組治療前后第1秒用力呼氣末容積(FEV1)差值比較,治療療程非7天亞組與7天亞組均無統(tǒng)計學(xué)意義〔MD=-0.03,95%CI(-0.11,0.05),P=0.45;MD=-0.01,95%CI(-0.06,0.03),P=0.61〕。兩組治療前后第1秒用力呼氣末容積占預(yù)計值百分比(FEV1%)差值比較,治療療程非7天亞組與7天亞組均無統(tǒng)計學(xué)意義〔MD=-0.80,95%CI(-2.62,1.02),P=0.39;MD=-0.21,95%CI(-1.44,1.03),P=0.74〕。兩組治療前后動脈血氧分壓(PaO2)差值比較,治療療程非7天亞組與7天亞組均有統(tǒng)計學(xué)意義〔MD=-2.12,95%CI(-4.14,-0.10),P=0.04;MD=-1.06,95%CI(-1.85,-0.26),P=0.01〕。兩組治療前后動脈血二氧化碳分壓(PaCO2)差值比較,治療療程非7天亞組與7天亞組均無統(tǒng)計學(xué)意義〔MD=-0.44,95%CI(-1.13,0.26),P=0.22;MD=0.00,95%CI(-0.58,0.57),P=0.99〕。兩組治療前后呼吸困難評分差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.02,95%CI(-0.18,0.13),P=0.76〕。兩組治療前后CAT差值比較,差異無統(tǒng)計學(xué)意義〔MD=0.34,95%CI(-0.23,0.92),P=0.24〕。對照組不良反應(yīng)主要表現(xiàn)為血糖升高、胃部不適和口干;試驗組不良反應(yīng)主要為口腔、咽部及胃部不適。結(jié)論 BUD和SCS均可改善AECOPD患者肺功能及動脈血氣、減輕呼吸困難和降低CAT評分,兩者療效差異不明顯,BUD不良反應(yīng)較SCS少。
布地奈德;全身性激素;肺疾病,慢性阻塞性;療效比較研究;Meta分析
徐飛,崔文強,吳曉,等.布地奈德與全身性激素治療COPD急性加重期療效的Meta分析[J].中國全科醫(yī)學(xué),2015,18(8):873-880.[www.chinagp.net]
Xu F,Cui WQ,Wu X,et al.Comparison of effect of budesonide and systemic corticosteroids on acute exacerbations of COPD:a meta-analysis[J].Chinese General Practice,2015,18(8):873-880.
COPD一般以老年人或具有吸煙史者高發(fā)[1]。我國COPD患者總數(shù)高達4 300萬[2-3],并且由于頻繁急性發(fā)作導(dǎo)致患者肺功能下降、醫(yī)療費用增加、生活質(zhì)量降低及病死率逐年升高。COPD病因是以炎癥為主[4]。根據(jù)病情嚴重程度可分為急性加重期(AECOPD)和緩解期。加拿大胸科協(xié)會(CTS)將AECOPD定義為呼吸困難持續(xù)加重、咳嗽加劇及痰量增多,治療用藥增多,或需聯(lián)合用藥[5]。治療AECOPD的常用藥物包括支氣管擴張劑、糖皮質(zhì)激素和抗生素等[1],激素可分為全身性激素(SCS)和局部性激素。由于AECOPD患者常表現(xiàn)為局部氣道炎癥加重[6],臨床上多采用SCS進行抗炎治療,但是短期大劑量SCS的使用常引起血糖增高、血壓升高和腸道反應(yīng);而吸入性糖皮質(zhì)激素(ICS),如布地奈德(BUD),作為一種局部性激素,對于治療AECOPD同樣具有療效,其直接作用于局部呼吸道,起效時間短,抗炎靶向性較強,且不良反應(yīng)較小。本研究對BUD和SCS治療AECOPD的效果進行系統(tǒng)評價,為臨床合理用藥提供循證醫(yī)學(xué)證據(jù)。
1.1 文獻納入與排除標(biāo)準(zhǔn)
1.1.1 納入標(biāo)準(zhǔn)
1.1.1.1 研究類型 BUD與SCS對比治療AECOPD的隨機對照試驗(RCT),語種限中、英文。
1.1.1.2 研究對象 AECOPD的患者診斷標(biāo)準(zhǔn):(1)有呼吸困難、慢性咳嗽或咳痰等臨床癥狀;(2)有危險因素(吸煙、職業(yè)、空氣污染等)暴露史;(3)吸入支氣管擴張劑后,肺功能檢查第1秒用力呼氣末容積(FEV1)與用力肺活量(FVC)比值 <70%,第1秒用力呼氣末容積占預(yù)計值百分比(FEV1%)為30%~50%?;颊咝詣e、年齡、病程、給藥方式不限。
1.1.1.3 干預(yù)措施 試驗組霧化吸入BUD,對照組口服或靜脈滴注糖皮質(zhì)激素,兩組制劑類型、用量、用法不限,余治療方法均相同。
1.1.1.4 觀察指標(biāo) 主要觀察指標(biāo):(1)肺功能(FEV1、FEV1%);(2)動脈血氣分析〔動脈血氧分壓(PaO2),動脈血二氧化碳分壓(PaCO2)〕、呼吸困難評分、COPD 評估測試(CAT)問卷、不良反應(yīng)。納入文獻的觀察指標(biāo)須包括肺功能或動脈血氣分析。
1.1.2 排除標(biāo)準(zhǔn) (1)動物實驗;(2)試驗組干預(yù)措施含其他吸入成分;(3)試驗組包含不同劑量BUD亞組的研究;(4)觀察指標(biāo)無具體數(shù)據(jù);(5)重復(fù)發(fā)表。
1.2 文獻檢索策略 計算機檢索PubMed、Web of Science、中國知網(wǎng)、維普網(wǎng)、中國生物醫(yī)學(xué)文獻數(shù)據(jù)庫(CBM),檢索時間均從建庫至2014年7月。英文檢索語句為“Budesonid AND (Systemic corticosteroids OR Corticosteroid OR Methylprednisolone OR Prednisone) AND (AECOPD OR Exacerbation of Chronic Obstructive Pulmonary Disease )”;中文檢索詞為“布地奈德、全身性激素(或甲強龍或強的松或潑尼松龍或潑尼松)、慢性阻塞性肺疾病(或AECOPD)”,并追蹤查閱相似文獻與參考文獻。
1.3 資料提取 根據(jù)事先自行制定的資料提取表格,由2名研究者獨立對納入研究的文獻進行全文閱讀并提取資料。當(dāng)意見不一致時,由第三者進行分析評定。對于資料不全或有歧義的文獻,則聯(lián)系作者獲取準(zhǔn)確結(jié)果。
1.4 偏倚風(fēng)險評價 根據(jù)Cochrane偏倚風(fēng)險評估工具RevMan 5.3對納入文獻進行偏倚風(fēng)險評估,包括6個方面:(1)是否采用隨機分配方法;(2)是否采用分配隱藏;(3)是否采用盲法;(4)結(jié)果數(shù)據(jù)是否完整;(5)是否無選擇性報道結(jié)果;(6)是否無其他偏倚來源。每條標(biāo)準(zhǔn)按照“是”“否”“不清楚”來劃分,分別表示偏倚風(fēng)險低、高和不確定。
1.5 統(tǒng)計學(xué)方法 采用Cochrane協(xié)作網(wǎng)提供的RevMan 5.3統(tǒng)計軟件進行統(tǒng)計分析。采用Q檢驗對文獻異質(zhì)性進行定性分析,I2檢驗對文獻異質(zhì)性進行定量分析,當(dāng)P≥0.10或I2≤50%時,表示各文獻無統(tǒng)計學(xué)異質(zhì)性,采用固定效應(yīng)模型分析;否則表示各文獻存在統(tǒng)計學(xué)異質(zhì)性,采用隨機效應(yīng)模型進行分析,若異質(zhì)性過大,則行描述性分析[7]。計量資料采用均數(shù)差(MD)表示,區(qū)間估計采用95%可信區(qū)間(95%CI)。以P<0.05為差異有統(tǒng)計學(xué)意義。
2.1 文獻檢索 檢索出相關(guān)文獻116篇,閱讀摘要后排除44篇,閱讀全文后,根據(jù)納入和排除標(biāo)準(zhǔn),共19篇文獻[8-26]符合納入標(biāo)準(zhǔn),其中中文18篇,英文1篇。文獻篩選流程圖見圖1,納入文獻的基本特征見表1。
2.2 偏倚風(fēng)險評估 僅4篇文獻[15,17,20,26]以隨機數(shù)字表法進行隨機分配,2篇文獻[17,26]提及盲法,各文獻均未提及分配隱藏、樣本量估算或采用意向性治療(ITT)分析(見表2)。
注:BUD=布地奈德,①=FEV1,②=FEV1%,③=PaO2,④=PaCO2,⑤=呼吸困難評分,⑥=COPD評估測試問卷,⑦=不良反應(yīng)
圖1 文獻篩選流程圖
2.3 Meta分析結(jié)果
2.3.1 FEV19篇文獻[8,10,12,14,16,19-20,24-25]報道了治療前后FEV1變化,根據(jù)療程分為非7天亞組3篇[10,16,20]和7天亞組6篇[8,12,14,19,24-25]。非7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.12,I2=53%),采用固定效應(yīng)模型。Meta分析顯示,兩組治療前后FEV1差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.03,95%CI(-0.11,0.05),P=0.45,見圖2〕。7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.95,I2=0),采用固定效應(yīng)模型進行分析。Meta分析顯示,兩組治療前后FEV1差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.01,95%CI(-0.06,0.03),P=0.61,見圖2〕。
圖2 兩組治療前后FEV1差值比較的森林圖
Figure 2 Forest plot for comparison of the differences of FEV1before and after treatment between the two groups
2.3.2 FEV1% 7篇文獻[11,13,15,17-18,22-23]報道了治療前后FEV1%變化,根據(jù)療程分為非7天亞組4篇[11,13,15,23]和7天亞組3篇[17-18,22]。非7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.74,I2=0),采用固定效應(yīng)模型。Meta分析顯示,兩組治療前后FEV1%差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.80,95%CI(-2.62,1.02),P=0.39,見圖3〕。7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.91,I2=0),采用固定效應(yīng)模型進行分析。Meta分析顯示,兩組治療前后FEV1%差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.21,95%CI(-1.44,1.03),P=0.74,見圖3〕。
圖3 兩組治療前后FEV1%差值比較的森林圖
Figure 3 Forest plot for comparison of the differences of FEV1% before and after treatment between the two groups
2.3.3 PaO217篇文獻[8-19,21-22,24-26]報道了治療前后PaO2變化,根據(jù)療程分為非7天亞組7篇[9-11,13,15-16,26]和7天亞組10篇[8,12,14,17-19,21-22,24-25]。非7天亞組各文獻間存在統(tǒng)計學(xué)異質(zhì)性(P<0.01,I2=74%),采用隨機效應(yīng)模型。Meta分析顯示,兩組治療前后PaO2差值比較,差異有統(tǒng)計學(xué)意義〔MD=-2.12,95%CI(-4.14,-0.10),P=0.04,見圖4〕。7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.73,I2=0),采用固定效應(yīng)模型進行分析。Meta分析顯示,兩組治療前后PaO2差值比較,差異有統(tǒng)計學(xué)意義〔MD=-1.06,95%CI(-1.85,-0.26),P=0.009,見圖4〕。
圖4 兩組治療前后PaO2差值比較的森林圖
Figure 4 Forest plot for comparison of the differences of PaO2before and after treatment between the two groups
2.3.4 PaCO217篇文獻[8-19,21-22,24-26]報道了治療前后PaCO2變化,根據(jù)療程分為非7天亞組7篇[9-11,13,15-16,26]和7天亞組10篇[8,12,14,17-19,21-22,24-25]。非7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.99,I2=0),采用固定效應(yīng)模型。Meta分析顯示,兩組治療前后PaCO2差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.44,95%CI(-1.13,0.26),P=0.22,見圖5〕。7天亞組各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.85,I2=0),采用固定效應(yīng)模型進行分析。Meta分析顯示,兩組治療前后PaCO2差值比較,差異無統(tǒng)計學(xué)意義〔MD=0.00,95%CI(-0.58,0.57),P=0.99,見圖5〕。
圖5 兩組治療前后PaCO2差值比較的森林圖
Figure 5 Forest plot for comparison of the differences of PaCO2before and after treatment between the two groups
2.3.5 呼吸困難評分 3篇文獻[18,22-23]報道了治療前后呼吸困難評分,各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.47,I2=0),采用固定效應(yīng)模型。Meta分析顯示,兩組治療前后呼吸困難評分差值比較,差異無統(tǒng)計學(xué)意義〔MD=-0.02,95%CI(-0.18,0.13),P=0.76,見圖6〕。
圖6 兩組治療前后呼吸困難評分差值比較的森林圖
Figure 6 Forest plot for comparison of the differences of dyspnea Scores before and after treatment between the two groups
2.3.6 CAT 2篇文獻[19-20]報道了治療前后CAT,各文獻間無統(tǒng)計學(xué)異質(zhì)性(P=0.25,I2=23%),采用固定效應(yīng)模型。Meta分析顯示,兩組治療前后CAT差值比較,差異無統(tǒng)計學(xué)意義〔MD=0.34,95%CI(-0.23,0.92),P=0.24,見圖7〕。
圖7 兩組治療前后CAT比較的Meta分析
Figure 7 Forest plot for Comparison of the differences of CAT before and after treatment between the two groups
2.3.7 不良反應(yīng) 13篇文獻[10,12-15,17-21,23,25-26]對不良反應(yīng)進行了監(jiān)測,綜合各文獻結(jié)果顯示,對照組不良反應(yīng)主要表現(xiàn)為血糖升高、胃部不適和口干;試驗組不良反應(yīng)主要表現(xiàn)為口腔、咽部及胃部不適(見表3)。
2.4 偏倚分析 分別對關(guān)于PaO2、PaCO2的文獻繪制漏斗圖(見圖8、9)。結(jié)果顯示,散點偏向左側(cè),漏斗圖對稱性差,存在一定程度的發(fā)表偏倚,可能與文獻質(zhì)量較低、樣本量小及其他偶然性因素等有關(guān)。
圖8 PaO2的發(fā)表偏倚的漏斗圖
組別例數(shù)血糖升高胃部不適(包括惡心)口干口腔不適(包括假絲酵母菌感染)咽部不適血壓升高其他合計對照組50541(8.1)34(6.4)14(2.8)1(0.2)0 6(1.2)3(0.6)99(19.6)試驗組5200 3(0.6)10(1.9)7(1.3)11(2.1)07(1.3)38(7.3)
圖9 PaCO2發(fā)表偏倚的漏斗圖
3.2 治療 臨床常選用SCS和ICS兩類激素治療AECOPD。SCS抗炎效果非常明顯,長期以來普遍用于治療AECOPD,但長期使用機體產(chǎn)生激素抵抗,治療效果下降[40],且其不良反應(yīng)較為嚴重。ICS同樣可有效治療AECOPD[41],BUD作為臨床上常用的ICS,不僅可以直接作用于氣道,顯著降低局部氣道炎癥反應(yīng)[42-43],還可以通過首過代謝降低全身炎性反應(yīng),降低外周血C反應(yīng)蛋白、血清IL-8和TNF-α水平[44]。此外,ICS與氣道上皮細胞內(nèi)糖皮質(zhì)受體結(jié)合,抑制促炎基因[45];也可提高Pro-SFTPB水平[46],抑制炎性反應(yīng)。
本研究結(jié)果顯示,BUD和SCS均可改善AECOPD患者肺功能及動脈血氣、減輕呼吸困難和降低CAT,除改善PaO2具有統(tǒng)計學(xué)意義外,其余療效差異無統(tǒng)計學(xué)意義??傮w來看,兩者療效接近。另外,BUD和SCS治療也均有不良反應(yīng)發(fā)生,BUD的不良反應(yīng)主要表現(xiàn)在消化系統(tǒng),如口干、咽部不適,胃部不適,嚴重者可出現(xiàn)上消化道出血。有研究顯示,BUD不良反應(yīng)較少且程度較輕[44],可長期使用[47],但長期使用會增加患肺炎的概率,且與BUD劑量呈正相關(guān)[48],需臨床應(yīng)用時注意。Sun等[47]研究發(fā)現(xiàn),BUD和甲潑尼龍SCS均可改善AECOPD臨床癥狀、肺功能、動脈血氣分析,且兩者無差異。值得注意的是,BUD不良反應(yīng)較輕,且聯(lián)合選擇性腎上腺素β2受體激動藥沙丁胺醇或福莫特羅可進一步提高AECOPD的治療效果[49]。但有文獻報道,ICS并不能改善AECOPD患者肺功能,即使大劑量使用也不能改善FEV1[50]。短期(2周)大劑量SCS也只能稍微改善肺功能,但可明顯增強總體治療效果,縮短住院時間,同時會出現(xiàn)嚴重的不良反應(yīng);長期(8周)使用其治療效果并未有所提升[51]。也有研究報道,SCS藥效迅速,尤其適用于AECOPD,而ICS是穩(wěn)定期COPD的關(guān)鍵藥物[52]。2014年《慢性阻塞性肺疾病全球倡議》(GOLD)也指出SCS為急性加重期的推薦藥物,可促進病情緩解和肺功能的恢復(fù),并且SCS治療AECOPD短療程5 d和常規(guī)療程14 d的急性加重率、病死率及FEV1改變均無差異,但目前尚未有足夠的證據(jù)對激素治療AECOPD的療程提供確切的結(jié)論。同時,GOLD指出ICS作為穩(wěn)定期的推薦藥物,需與長效β2受體激動劑聯(lián)合應(yīng)用,同樣此方案尚缺乏臨床證據(jù),其治療AECOPD是否有效未提及[1]。
綜上所述,BUD和SCS治療AECOPD均具有顯著療效,兩者療效差異不明顯。由于語種的限制,本研究只納入中、英文文獻,國內(nèi)文獻占多數(shù),對符合標(biāo)準(zhǔn)的其他語種類文獻未進行統(tǒng)計分析;納入文獻大多數(shù)未詳細描述隨機的方法、具體的分配隱藏方法、盲法和退出、失訪、隨訪情況,多數(shù)文獻質(zhì)量不高,因此,本研究結(jié)果與GOLD存在一定的差異,SCS和BUD治療AECOPD的劑量、療程、療效以及不良反應(yīng)等有待臨床進一步探索與驗證。
[1]Global Initiative for Chronic Obstructive Lung Disease(Revised 2014)[EB/OL].http://www.goldcopd.org.
[2]楊璞.專家為您解讀COPD[N].中國中醫(yī)藥報,2014-11-27(1).
[3]Mu L.The efficacy of Xuebijing in the treatment of chronic obstructive pulmonary disease in exacerbations[J].Chinese Journal of Clinical Rational Drug Use,2014,7(9):136-137.(in Chinese) 穆林.血必凈注射液治療慢性阻塞性肺病急性加重期的療效觀察[J].臨床合理用藥雜志,2014,7(9):136-137.
[4]Caramori G,Adcock IM,Stefano A,et al.Cytokine inhibition in the treatment of COPD[J].Int J Chron Obstruct Pulmon Dis,2014(9):397-412.
[5]McKenna P,MacLeod K,Le C,et al.Management of acute exacerbation of COPD in rural Alberta emergency departments[J].Can J Rural Med,2015,20(1):7-14.
[6]Chin CL,Manzel LJ,Lehman EE,et al.Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers[J].Am J Respir Crit Care Med,2005,172(1):85-91.
[7]Zhou ZR,Zhu XD,Liang ZG,et al.Hormonal therapy plus radiotherapy for prostate cancer in different treatment courses:a meta-analysis [J].Chinese Journal of Evidence-Based Medicine,2012,12(10):1195-1202.(in Chinese) 周支瑞,朱小東,梁忠國,等.放療聯(lián)合不同療程激素治療前列腺癌療效和安全性的Meta分析[J].中國循證醫(yī)學(xué)雜志,2012,12(10):1195-1202.
[8]Chen GZ,Xu HW,Zhang Q,et al.The effect of inhaled budesonide in persons with a cute exacerbations of chronic obstructive pulmonary disease[J].Chinese General Practice,2005,8(10):1667-1668.(in Chinese) 陳國忠,徐輝文,張琦,等.吸入布地奈德治療慢性阻塞性肺疾病急性加重期的療效研究[J].中國全科醫(yī)學(xué),2005,8(10):1667-1668.
[9]Zhang XY,Zheng CX,Zhou W,et al.Compare the efficacy of budesonide inhalation and intravenous prednisolone in treatment of acute exacerbations of chronic obstructive pulmonary disease[J].Chinese Journal of Gerontology,2006,26(8):1050-1051.(in Chinese) 張星宇,鄭翠俠,周巍,等.霧化吸入布地奈德和靜脈用潑尼松龍治療慢性阻塞性肺病急性加重期療效比較[J].中國老年學(xué)雜志,2006,26(8):1050-1051.
[10]謝艷萍,聶森,王建春,等.霧化吸入布地奈德混懸液在慢性阻塞性肺疾病急性加重期的作用[C].湖州:2007年(第二十九屆)浙江省醫(yī)學(xué)會呼吸病學(xué)學(xué)術(shù)年會,2007.
[11]Cao TT,Cheng Z.Compare the efficacy of budesonide with methylprednisolone in tne acute exacerbation period of COPD[J].Journal of Medical Forum,2008,29(14):89-90.(in Chinese) 曹婷婷,程哲.布地奈德與甲基強的松龍在COPD急性加重期療效比較[J].醫(yī)藥論壇雜志,2008,29(14):89-90.
[12]Wang JZ,Zuo XH.The comparative analysis of the efficacy of hormone inhalation and systemic application in the treatment of AECOPD[J].Journal of Clinical Pulmonary Medicine,2009,14(9):1218-1219.(in Chinese) 王建筑,左現(xiàn)海.激素霧化吸入與全身性應(yīng)用治療AECOPD的療效比較分析[J].臨床肺科雜志,2009,14(9):1218-1219.
[13]Yan ZC,Liu YH.Clinical efficacy of inhalation of oxygen-driven aerosols of budesonide for acute exacerbationg phase of chronic obstructive pulmonary disease[J].Chinese Modern Doctor,2009,47(30):44-45.(in Chinese) 閆忠誠,劉穎卉.布地奈德混懸液氧驅(qū)動霧化治療AECOPD療效分析[J].中國現(xiàn)代醫(yī)生,2009,47(30):44-45.
[14]Yang XY,Tang BS,Huang YQ,et al.The efficacy of budesonide inhalation in the therapy of AECOPD[J].Journal of Clinical Research,2010,27(6):1113-1114.(in Chinese) 楊湘永,唐炳松,黃藝群,等.布地奈德霧化吸入治療AECOPD的療效觀察[J].醫(yī)學(xué)臨床研究,2010,27(6):1113-1114.
[15]王艷飛,薛燕,王紅燕,等.霧化吸入與全身應(yīng)用糖皮質(zhì)激素在AECOPD中的臨床研究[J].實用心腦肺血管病雜志,2011,19(3):361-362.
[16]Xue JF.Analysis of inhaling budesonide in the treatment of a cute exacerbations of chronic obstructive pulmonary disease[J].Journal of Clinical Lung,2011,16(8):1173-1174.(in Chinese) 薛金鳳.霧化吸入布地奈德混懸液治療AECOPD療效分析[J].臨床肺科雜志,2011,16(8):1173-1174.
[17]雷蕾.布地奈德霧化吸入治療慢性阻塞性肺疾病急性加重期的臨床研究[D].西安:第四軍醫(yī)大學(xué),2011.
[18]Zhang MJ.Clinical observation of curative effect of high-dose inhaled corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease[J].Journal of Clinical Lung,2013,18(7):1250-1251.(in Chinese) 章明杰.吸入大劑量糖皮質(zhì)激素對AECOPD療效的臨床觀察[J].臨床肺科雜志,2013,18(7):1250-1251.
[19]莫萬勇,李再清,肖進國,等.布地奈德霧化治療慢性阻塞性肺疾病急性加重期臨床觀察[J].中外醫(yī)療,2013,32(25):118-119.
[20]Hu BD,Ding Z.Clinical analysis of efficacy of budesonideatomizing in halationin elderly patients with AECOPD[J].Journal of Clinical Pulmonary Medicine,2013,18(12):2184-2186.(in Chinese) 胡碧丹,丁震.霧化吸入布地奈德在AECOPD中的療效分析[J].臨床肺科雜志,2013,18(12):2184-2186.
[21]符大俠.甲潑尼松龍與布地奈德分別治療64例慢性阻塞性肺疾病急性加重期的療效比較[J].中國民族民間醫(yī)藥,2014,3:69-70.
[22]王慎臨,陳更亞.糖皮質(zhì)激素治療慢性阻塞性肺疾病急性加重期的效果觀察[J].寧夏醫(yī)學(xué)雜志,2014,36(5):424-426.
[23]He RL.Analysis of atomization inhalation of budesonide in the treatment of acute exacerbations of chronic obstructive pulmonary disease[J].Chinese Journal of Modern Drug Application,2014,11:38-40.(in Chinese) 和瑞蓮.霧化吸入布地奈德混懸液治療慢性阻塞性肺疾病急性加重期的療效分析[J].中國現(xiàn)代藥物應(yīng)用,2014,11:38-40.
[24]王俊霞,李淑媛,郝志芳,等.霧化吸入布地奈德混懸液在AECOPD的作用[J].臨床肺科雜志,2008,13(7):860.
[25]Zhou X,Han W.Effect of nebulized budesonide on acute exacerbations of chronic obstructive pulmonary disease with severe restriction of airflow[J].Shanghai Medical Journal,2004,27(12):882-885.(in Chinese) 周新,韓偉.布地奈德溶液霧化在重度慢性阻塞性肺疾病急性加重期的應(yīng)用[J].上海醫(yī)學(xué),2004,27(12):882-885.
[26] Maltais F,Ostinelli J,Bourbeau J,et al.Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease:a randomized controlled trial[J].Am J Respir Crit Care Med,2002,165(5):695-703.
[27]Welte T,Groneberg DA.Asthma and COPD[J].Exp Toxicol Pathol,2006,57(Suppl 2):35-40.
[28]Reid DJ,Carlson A.Clinical use of aclidinium in patients with COPD[J].Int Journal Chron Obstruct Pulmon Dis,2014,9:369-379.
[29]Harkness LM,Kanabar V,Sharma HS,et al.Pulmonary vascular changes in asthma and COPD[J].Pulm Pharmacol Ther,2014,29(2):144-155.
[30]Saetta M,Baraldo S,Zuin R.Neutrophil chemokines in severe exacerbations of chronic obstructive pulmonary disease:fatal chemo-attraction?[J].Am J Respir Crit Care Med,2013,168(8):911-913.
[31]Zhu J,Qiu YS,Majumdar S,et al.Exacerbations of Bronchitis:bronchial eosinophilia and gene expression for interleukin-4,interleukin-5,and eosinophil chemoattractants[J].Am J Respir Crit Care Med,2001,164(1):109-116.
[32]Gayan-Ramirez G,Decramer M.Mechanisms of striated muscle dysfunction during acute exacerbations of COPD[J].J Appl Physiol,2013,114(9):1291-1299.
[33]Jeffery PK.Remodeling and inflammation of bronchi in asthma and chronic obstructive pulmonary disease[J].Proc Am Thorac Soc,2004,1(3):176-183.
[34]Wedzicha JA,Singh R,Mackay AJ.Acute COPD exacerbations[J].Clin Chest Med,2014,35(1):157-163.
[35]MacNee W.Systemic inflammatory biomarkers and co-morbidities of chronic obstructive pulmonary disease[J].Annals Med,2013,45(3):291-300.
[36]Rochat T.COPD:a disease with systemic inflammation[J].Rev Mal Respir,2012,29(4):537-544.
[38]Mat Z,Grensemann B,Yakin Y,et al.Effect of lipoteichoic acid on IL-2 and IL-5 release from T lymphocytes in asthma and COPD[J].Int Immunopharmacol,2012,13(3):284-291.
[39]Fujimoto K.Up-to-date COPD treatment[J].Rinsho Byori,2014,62(5):471-477.
[40]Walters JA,Wang W,Morley C,et al.Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease[J].Cochrane Database Syst Rev,2011,10:CD006897.
[41]Cates C.Inhaled corticosteroids in COPD:quantifying risks and benefits[J].Thorax,2013,68(6):499-500.
[42]Jatakanon A,Kharitonov S,Lim S,et al.Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma[J].Thorax,1999,54(2):108-114.
[43]Gauvreau GM,Doctor J,Watson RM,et al.Effects of inhaled budesonide on allergen-induced airway responses and airway inflammation[J].Am J Respir Crit Care Med,1996,154(5):1267-1271.
[44]Gaude GS,Nadagouda S.Nebulized corticosteroids in the management of acute exacerbation of COPD[J].Lung India,2010,27(4):230-235.
[45]Hodgson D,Mortimer K,Harrison T.Budesonide/formoterol in the treatment of asthma[J].Expert Rev Respir Med,2010,4(5):557-566.
[46]Um SJ,Lam S,Coxson H,et al.Budesonide/formoterol enhances the expression of pro surfactant protein-B in lungs of COPD patients[J].PLoS One,2013,8(12):e83881.
[47]Sun X,He Z,Zhang J,et al.Compare the efficacy of inhaled budesonide and systemic methylprednisolone on systemic inflammation of AECOPD[J].Pulm Pharmacol Ther,2014.doi:10.1016/j.pupt.2014.09.004.
[48]White P.Inhaled fluticasone and budesonide increased the risk of serious pneumonia in COPD[J].Evid Based Med,2014,19(3):116.
[49]Lazarinis N,Jorgensen L,Ekstrom T,et al.Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction[J].Thorax,2014,69(2):130-136.
[50]Saha S,Siva R,Brightling CE,et al.COPD:an inhaled corticosteroid-resistant,oral corticosteroid-responsive condition[J].Eur Respir J,2006,27(4):863-865.
[51]Homed A,Boushey MD.Glucocorticoid therapy for chronic obstructive pulmonary disease[J].New Eng J Med,1999,340(25):1990-1991.
[52]Nakawah MO,Hawkins C,Barbandi F.Asthma,chronic obstructive pulmonary disease (COPD),and the overlap syndrome[J].J Am Board Fam Med,2013,26(4):470-477.
(本文編輯:吳立波)
Comparison of Effect of Budesonide and Systemic Corticosteroids on Acute Exacerbations of COPD:A Meta-analysis
XUFei,CUIWen-qiang,WUXiao,etal.
DepartmentofIntegrativeMedicine,HuashanHospitalAffiliatedtoFudanUniversity,InstituteofIntegratedTraditionalChineseandWesternMedicine,FudanUniversity,Shanghai200040,China
Objective To systematically review the efficacy and safety of budesonide(BUD) and systemic corticosteroids(SCS) on patients with AECOPD.Methods We searched literature concerning studies in which patients with AECOPD receiving BUD treatment were assigned as trial group and SCS as control group from PubMed,Web of Science,CNKI,VIP database and CBM Data with the time range of searching set from establishment of the databases to July 2014.The extracted data covered pulmonary function analysis,arterial blood gas analysis,score of dyspnea,score of CAT and adverse events.Results A total of 19 pieces of valid literature were included.The meta analysis showed that there was no significant difference in FEV1before and after treatment either in non-seven-day treatment subgroup or seven-day treatment subgroup〔MD=-0.03,95%CI(-0.11,0.05),P=0.45;MD=-0.01,95%CI(-0.06,0.03),P=0.61〕;there was no significant difference in FEV1% before and after treatment either in non-seven-day treatment subgroup or seven-day treatment subgroup〔MD=-0.80,95%CI(-2.62,1.02),P=0.39;MD=-0.21,95%CI(-1.44,1.03),P=0.74〕;there was significant difference in PaO2before and after treatment both in non-seven-day treatment subgroup and seven-day treatment subgroup〔MD=-2.12,95%CI(-4.14,-0.10),P=0.04;MD=-1.06,95%CI(-1.85,-0.26),P=0.01〕;there was no significant difference in PaCO2before and after treatment either in non-seven-day treatment subgroup or seven-day treatment subgroup〔MD=-0.44,95%CI(-1.13,0.26),P=0.22;MD=0.00,95%CI(-0.58,0.57),P=0.99〕;there was no significant difference in the scores of dyspnea〔MD=-0.02,95%CI(-0.18,0.13),P=0.76〕;there was no significant difference in CAT〔MD=0.34,95%CI(-0.23,0.92),P=0.24〕.For trial group,the adverse events were mainly increasing level of blood glucose,stomach upset and xerostomia;for control group,the adverse events were mainly discomfort in oral cavity,throat and stomach.Conclusion BUD and SCS are both effective in improving pulmonary function and arterial blood gas,alleviating dyspnea and reducing CAT score in patients with AECOPD.The difference in the effects is not statistically significant and BUD causes less adverse events than SCS.
Budesonid;Systemic corticosteroids;Pulmonary disease,chronic obstructive;Comparative effectiveness research;Meta-analysis
國家自然科學(xué)基金面上項目(81173390);上海市惲氏中西醫(yī)匯通項目
200040上海市,復(fù)旦大學(xué)附屬華山醫(yī)院中西醫(yī)結(jié)合科,復(fù)旦大學(xué)中西醫(yī)結(jié)合研究所(徐飛,吳曉,董競成);復(fù)旦大學(xué)上海醫(yī)學(xué)院中西醫(yī)結(jié)合基礎(chǔ)系(崔文強)
董競成,200040上海市,復(fù)旦大學(xué)附屬華山醫(yī)院中西醫(yī)結(jié)合科,復(fù)旦大學(xué)中西醫(yī)結(jié)合研究所;E-mail:jcdong2004@126.com
R 563.9
A
10.3969/j.issn.1007-9572.2015.08.005
發(fā)表時間(年)隨機方法分配隱藏盲法結(jié)果數(shù)據(jù)完整性無選擇性報告陳國忠[8]2005不清楚不清楚否是是張星宇[9]2006不清楚不清楚否是是謝艷萍[10]2007不清楚不清楚否是是曹婷婷[11]2008不清楚不清楚否是是王建筑[12]2009不清楚不清楚否是是閆忠誠[13]2009不清楚不清楚否是是楊湘永[14]2010不清楚不清楚否是是王艷飛[15]2011隨機數(shù)字表不清楚否否是薛金鳳[16]2011不清楚不清楚否是是雷蕾[17]2011隨機數(shù)字表不清楚雙盲是是章明杰[18]2013不清楚不清楚否是是莫萬勇[19]2013不清楚不清楚否是是胡碧丹[20]2013隨機數(shù)字表不清楚否是是符大俠[21]2014不清楚不清楚否是是王慎臨[22]2014就診順序不清楚否是是和瑞蓮[23]2014不清楚不清楚否是是王俊霞[24]2008不清楚不清楚否是是周新[25]2004不清楚不清楚否是是Maltais[26]2002隨機數(shù)字表不清楚三盲否是
2014-12-20;
2015-02-10)