Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease.
Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease.
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DOI：
10.1002/14651858.cd006829.pub2
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发表时间：
2012-09-12
影响因子：
8.4
通讯作者：
Poole, Phillippa
中科院分区：
文献类型：
--
作者：
Javier Nannini, Luis;Lasserson, Toby J.;Poole, Phillippa
关键词：
Adrenal Cortex Hormones [*administration & dosage; adverse effects]Adrenergic beta-Agonists [*administration & dosage; adverse effects]Bronchodilator Agents [administration & dosage; adverse effects]Drug CombinationsDrug Therapy, CombinationNebulizers and VaporizersPneumonia [chemically induced]Pulmonary Disease, Chronic Obstructive [*drug therapy; mortality]Quality of LifeRandomized Controlled Trials as TopicAdultHumans
吸入性类固醇（ICS）和长效β 2受体激动剂（LABA）都用于慢性阻塞性肺疾病（COPD）的治疗。这篇更新的综述比较了复方LABA加ICS治疗（LABA/ICS）与LABA组分药物单独给药。评估ICS和LABA在单一吸入器中与单组分LABA单独治疗COPD成人的疗效。我们检索了科克伦航空集团专业试验注册。最近一次检索日期为2011年11月。我们纳入了随机、双盲对照试验。我们纳入了在COPD患者中比较复方ICS和LABA制剂及其组分LABA制剂的试验。两位作者独立评估了研究偏倚风险并提取了数据。主要结局为急性加重、死亡率和肺炎，次要结局为健康相关生活质量（通过有效量表测量）、肺功能、因缺乏疗效而退出研究、因不良事件和副作用而退出研究。二分数据分析为随机效应模型比值比或率比，95%置信区间（CI），连续数据分析为平均差异和95% CI。根据GRADE工作组的建议，我们对急性加重、死亡率和肺炎的证据质量进行了评价。14项研究符合纳入标准，随机分配了11，794名重度COPD患者。我们观察了任何LABA + ICS吸入器（LABA/ICS）与单独使用相同LABA组分的情况，然后我们分别观察了10项评估氟替卡松+沙美特罗（FPS）的研究和4项评估布地奈德+福莫特罗（BDF）的研究。这些研究设计良好，随机化和设盲的偏倚风险较低，但脱落率较高，这降低了我们对死亡率以外结局结果的信心。9项随机化9921例受试者的研究中，低质量证据表明使用LABA/ICS吸入器的患者的急性加重率低于单独使用LABA的患者（率比0.76; 95% CI 0.68 - 0.84）。这相当于LABA组每人每年发生1次急性加重，ICS/LABA组每人每年发生0.76次急性加重。我们对这一效应的信心受到研究结果之间的统计异质性（I2 = 68%）和研究间高退出率偏倚风险的限制。当分析研究过程中发生一次或多次急性加重的人数时，FPS降低了急性加重的几率，比值比（OR）为0.83（95% CI 0.70至0.98，6项研究，3357例受试者）。LABA组在一年内加重的风险为47%，预计接受LABA/ICS治疗的患者中有42%会发生加重。对报告偏差影响的担忧导致我们将这种影响的证据质量从高降级为中等。住院率无显著差异（率比0.79; 95% CI 0.55 - 1.13，由于偏倚风险、统计学不精确性和不一致性，证据质量极低）。根据10项研究（10，680名参与者），使用联合吸入器的患者与使用LABA的患者之间的死亡率无显著差异（OR 0.92; 95%CI 0.76至1.11，由于统计不精确，降级为中等质量证据）。肺炎在随机分配至联合吸入器组的人群中更常见，来自12项研究（11，076例受试者）（OR 1.55; 95% CI 1.20 - 2.01，由于与损耗相关的偏倚风险，中等质量证据），LABA单药治疗的年风险约为3%，而联合治疗的年风险为4%。在增加不同剂量或类型吸入性皮质类固醇的试验中，急性加重或肺炎的结果之间没有显著差异。ICS/LABA在改善由St乔治呼吸问卷测量的健康相关生活质量方面比单独使用LABA更有效（FPS低1.58个单位; BDF降低2.69个单位），呼吸困难（FPS组降低0.09单位），症状（使用BDF时降低0.07个单位），急救药物（FPS组每天减少0.38揿，BDF组每天减少0.33揿）和一秒用力呼气量（FEV1）（FPS高70 mL，BDF高50 mL）。与SAL相比，FPS更易发生念珠菌病（OR 3.75）和上呼吸道感染（OR 1.32）。我们没有将与念珠菌病相关的联合收割机不良事件数据合并用于BDF研究，因为结果非常不一致。对研究数据的分析和可用性的担忧使人们对ICS/LABA在预防急性加重方面优于单独使用LABA提出了质疑。对住院的影响不一致，需要进一步探索。有中等质量的证据表明ICS/LABA会增加肺炎的风险。有中等质量的证据表明，治疗对死亡率有类似的影响。ICS/LABA组的生活质量、症状评分、急救药物使用和FEV1改善程度高于LABA组，但这些结局的平均差异可能无临床意义。对于个体患者，肺炎风险的增加需要与急性加重的可能减少相平衡。更多关于使用不同剂量吸入性皮质类固醇的组合吸入器的相对益处和不良事件发生率的信息将是有用的。需要头对头比较的证据来评估不同组合吸入器的相对风险和益处。
Both inhaled steroids (ICS) and long-acting beta2-agonists (LABA) are used in the management of chronic obstructive pulmonary disease (COPD). This updated review compared compound LABA plus ICS therapy (LABA/ICS) with the LABA component drug given alone. To assess the efficacy of ICS and LABA in a single inhaler with mono-component LABA alone in adults with COPD. We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search was November 2011. We included randomised, double-blind controlled trials. We included trials comparing compound ICS and LABA preparations with their component LABA preparations in people with COPD. Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia, while secondary outcomes were health-related quality of life (measured by validated scales), lung function, withdrawals due to lack of efficacy, withdrawals due to adverse events and side-effects. Dichotomous data were analysed as random-effects model odds ratios or rate ratios with 95% confidence intervals (CIs), and continuous data as mean differences and 95% CIs. We rated the quality of evidence for exacerbations, mortality and pneumonia according to recommendations made by the GRADE working group. Fourteen studies met the inclusion criteria, randomising 11,794 people with severe COPD. We looked at any LABA plus ICS inhaler (LABA/ICS) versus the same LABA component alone, and then we looked at the 10 studies which assessed fluticasone plus salmeterol (FPS) and the four studies assessing budesonide plus formoterol (BDF) separately. The studies were well-designed with low risk of bias for randomisation and blinding but they had high rates of attrition, which reduced our confidence in the results for outcomes other than mortality. There was low quality evidence that exacerbation rates in people using LABA/ICS inhalers were lower in comparison to those with LABA alone, from nine studies which randomised 9921 participants (rate ratio 0.76; 95% CI 0.68 to 0.84). This corresponds to one exacerbation per person per year on LABA and 0.76 exacerbations per person per year on ICS/LABA. Our confidence in this effect was limited by statistical heterogeneity between the results of the studies (I2 = 68%) and a risk of bias from the high withdrawal rates across the studies. When analysed as the number of people experiencing one or more exacerbations over the course of the study, FPS lowered the odds of an exacerbation with an odds ratio (OR) of 0.83 (95% CI 0.70 to 0.98, 6 studies, 3357 participants). With a risk of an exacerbation of 47% in the LABA group over one year, 42% of people treated with LABA/ICS would be expected to experience an exacerbation. Concerns over the effect of reporting biases led us to downgrade the quality of evidence for this effect from high to moderate. There was no significant difference in the rate of hospitalisations (rate ratio 0.79; 95% CI 0.55 to 1.13, very low quality evidence due to risk of bias, statistical imprecision and inconsistency). There was no significant difference in mortality between people on combined inhalers and those on LABA, from 10 studies on 10,680 participants (OR 0.92; 95% CI 0.76 to 1.11, downgraded to moderate quality evidence due to statistical imprecision). Pneumonia occurred more commonly in people randomised to combined inhalers, from 12 studies with 11,076 participants (OR 1.55; 95% CI 1.20 to 2.01, moderate quality evidence due to risk of bias in relation to attrition) with an annual risk of around 3% on LABA alone compared to 4% on combination treatment. There were no significant differences between the results for either exacerbations or pneumonia from trials adding different doses or types of inhaled corticosteroid. ICS/LABA was more effective than LABA alone in improving health-related quality of life measured by the St George’s Respiratory Questionnaire (1.58 units lower with FPS; 2.69 units lower with BDF), dyspnoea (0.09 units lower with FPS), symptoms (0.07 units lower with BDF), rescue medication (0.38 puffs per day fewer with FPS, 0.33 puffs per day fewer with BDF), and forced expiratory volume in one second (FEV1) (70 mL higher with FPS, 50 mL higher with BDF). Candidiasis (OR 3.75) and upper respiratory infection (OR 1.32) occurred more frequently with FPS than SAL. We did not combine adverse event data relating to candidiasis for BDF studies as the results were very inconsistent. Concerns over the analysis and availability of data from the studies bring into question the superiority of ICS/LABA over LABA alone in preventing exacerbations. The effects on hospitalisations were inconsistent and require further exploration. There was moderate quality evidence of an increased risk of pneumonia with ICS/LABA. There was moderate quality evidence that treatments had similar effects on mortality. Quality of life, symptoms score, rescue medication use and FEV1 improved more on ICS/LABA than on LABA, but the average differences were probably not clinically significant for these outcomes. To an individual patient the increased risk of pneumonia needs to be balanced against the possible reduction in exacerbations. More information would be useful on the relative benefits and adverse event rates with combination inhalers using different doses of inhaled corticosteroids. Evidence from head-to-head comparisons is needed to assess the comparative risks and benefits of the different combination inhalers.