鼻内用类固醇与安慰剂或不干预治疗慢性鼻-鼻窦炎的比较
Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis.
作者信息
Chong Lee Yee, Head Karen, Hopkins Claire, Philpott Carl, Schilder Anne G M, Burton Martin J
机构信息
UK Cochrane Centre, Oxford, UK.
出版信息
Cochrane Database Syst Rev. 2016 Apr 26;4(4):CD011996. doi: 10.1002/14651858.CD011996.pub2.
BACKGROUND
This review is one of six looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and is characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. The use of topical (intranasal) corticosteroids has been widely advocated for the treatment of chronic rhinosinusitis given the belief that inflammation is a major component of this condition.
OBJECTIVES
To assess the effects of intranasal corticosteroids in people with chronic rhinosinusitis.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) with a follow-up period of at least three months comparing intranasal corticosteroids (e.g. beclomethasone dipropionate, triamcinolone acetonide, flunisolide, budesonide) against placebo or no treatment in patients with chronic rhinosinusitis.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity and the commonest adverse event - epistaxis. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score and the adverse events of local irritation or other systemic adverse events. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
MAIN RESULTS
We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no intervention Only one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence).Our second primary outcome, disease severity , was measured using the Chronic Sinusitis Survey in a second study (134 participants without polyps), which found no important difference (mean difference (MD) 2.84, 95% confidence interval (CI) -5.02 to 10.70; scale 0 to 100). Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group (RR 2.78, 95% CI 1.76 to 4.40; 109 participants). The quality of the evidence was low.Six studies provided data on at least two of the individual symptoms used in the EPOS 2012 criteria to define chronic rhinosinusitis (nasal blockage, rhinorrhoea, loss of sense of smell and facial pain/pressure). When all four symptoms in the EPOS criteria were available on a scale of 0 to 3 (higher = more severe symptoms), the average MD in change from baseline was -0.26 (95% CI -0.37 to -0.15; 243 participants; two studies; low quality evidence). Although there were more studies and participants when only nasal blockage and rhinorrhoea were considered (MD -0.31, 95% CI -0.38 to -0.24; 1702 participants; six studies), the MD was almost identical to when loss of sense of smell was also considered (1345 participants, four studies; moderate quality evidence).When considering the results for the individual symptoms, benefit was shown in the intranasal corticosteroids group. The effect size was larger for nasal blockage (MD -0.40, 95% CI -0.52 to -0.29; 1702 participants; six studies) than for rhinorrhoea (MD -0.25, 95% CI -0.33 to -0.17; 1702 participants; six studies) or loss of sense of smell (MD -0.19, 95% CI -0.28 to -0.11; 1345 participants; four studies). There was heterogeneity in the analysis for facial pain/pressure (MD -0.27, 95% CI -0.56 to 0.02; 243 participants; two studies). The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure.There was an increased risk of epistaxis with intranasal corticosteroids (risk ratio (RR) 2.74, 95% CI 1.88 to 4.00; 2508 participants; 13 studies; high quality evidence).Considering our secondary outcome, general HRQL, one study (134 participants without polyps) measured this using the SF-36 and reported a statistically significant benefit only on the general health subscale. The quality of the evidence was very low.It is unclear whether there is a difference in the risk of local irritation (RR 0.94, 95% CI 0.53 to 1.64; 2124 participants; 11 studies) (low quality evidence).None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis or stunted growth (children). Other comparisons We identified no other studies that compared intranasal corticosteroids plus co-intervention A versus placebo plus co-intervention A.
AUTHORS' CONCLUSIONS: Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life (very low quality evidence). For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).
背景
本综述是针对慢性鼻窦炎患者主要药物治疗方案的六项综述之一。慢性鼻窦炎很常见,其特征是鼻腔和鼻窦内衬的炎症,导致鼻塞、流涕、面部压迫感/疼痛和嗅觉丧失。该病症可伴有或不伴有鼻息肉。鉴于炎症是这种病症的主要组成部分,局部(鼻内)使用皮质类固醇已被广泛提倡用于治疗慢性鼻窦炎。
目的
评估鼻内皮质类固醇对慢性鼻窦炎患者的疗效。
检索方法
Cochrane耳鼻喉信息专家检索了Cochrane耳鼻喉试验注册库;对照试验中央注册库(CENTRAL 2015年第8期);医学期刊数据库;荷兰医学文摘数据库;临床试验.gov;国际临床试验注册平台及其他已发表和未发表试验的来源。检索日期为2015年8月11日。
选择标准
随访期至少三个月的随机对照试验(RCT),比较鼻内皮质类固醇(如二丙酸倍氯米松、曲安奈德、氟尼缩松、布地奈德)与安慰剂或不治疗对慢性鼻窦炎患者的疗效。
数据收集与分析
我们采用了Cochrane预期的标准方法程序。我们的主要结局是疾病特异性健康相关生活质量(HRQL)、患者报告的疾病严重程度以及最常见的不良事件——鼻出血。次要结局包括一般HRQL、鼻内镜下鼻息肉评分、计算机断层扫描(CT)扫描评分以及局部刺激或其他全身不良事件的不良事件。我们使用GRADE评估每个结局的证据质量;这在文中用斜体表示。
主要结果
我们纳入了18项RCT,共2738名参与者。14项研究的参与者有鼻息肉,4项研究的参与者没有鼻息肉。只有一项研究是在儿童中进行的。鼻内皮质类固醇与安慰剂或无干预相比只有一项研究(20名无息肉的成年参与者)使用鼻窦炎结局测量-31(RSOM-31)测量了我们的主要结局疾病特异性HRQL。他们报告无显著差异(无数值数据)(极低质量证据)。我们的第二个主要结局疾病严重程度,在第二项研究(134名无息肉的参与者)中使用慢性鼻窦炎调查进行测量,未发现重要差异(平均差(MD)2.84,95%置信区间(CI)-5.02至10.70;量表0至100)。另一项研究(伴有鼻息肉的慢性鼻窦炎)报告鼻内皮质类固醇组改善的机会增加(RR 2.78,95% CI 1.76至4.40;109名参与者)。证据质量低。六项研究提供了关于2012年欧洲鼻窦炎和鼻息肉意见书(EPOS)标准中用于定义慢性鼻窦炎的至少两种个体症状的数据(鼻塞、流涕、嗅觉丧失和面部疼痛/压迫感)。当EPOS标准中的所有四种症状在0至3的量表上可用时(分数越高 = 症状越严重),从基线变化的平均MD为-0.26(95% CI -0.37至-0.15;243名参与者;两项研究;低质量证据)。尽管仅考虑鼻塞和流涕时研究和参与者更多(MD -0.31,95% CI -0.38至-0.24;1702名参与者;六项研究),但MD与也考虑嗅觉丧失时几乎相同(1345名参与者,四项研究;中等质量证据)。在考虑个体症状的结果时,鼻内皮质类固醇组显示出益处。鼻塞的效应量(MD -0.40,95% CI -0.52至-0.29;1702名参与者;六项研究)大于流涕(MD -0.25,95% CI -0.33至-0.17;1702名参与者;六项研究)或嗅觉丧失(MD -0.19,95% CI -0.28至-0.11;1345名参与者;四项研究)。面部疼痛/压迫感的分析存在异质性(MD -0.27,95% CI -0.56至0.02;243名参与者;两项研究)。鼻塞、流涕和嗅觉丧失的证据质量为中等,但面部疼痛/压迫感的证据质量为低。鼻内皮质类固醇导致鼻出血的风险增加(风险比(RR)2.74,95% CI 1.88至4.00;2508名参与者;13项研究;高质量证据)。考虑我们的次要结局一般HRQL,一项研究(134名无息肉的参与者)使用SF-36进行测量,仅在一般健康子量表上报告了统计学上的显著益处。证据质量极低。尚不清楚局部刺激风险是否存在差异(RR 0.94,95% CI 0.53至1.64;2124名参与者;11项研究)(低质量证据)。没有一项研究对患者进行足够长时间的治疗或随访,以提供关于骨质疏松症风险或生长发育迟缓(儿童)的有意义数据。其他比较我们未发现其他比较鼻内皮质类固醇加联合干预A与安慰剂加联合干预A的研究。
作者结论
现有大多数证据来自慢性鼻窦炎伴鼻息肉患者的研究。关于生活质量的信息很少(极低质量证据)。对于疾病严重程度,似乎所有症状都有改善(低质量证据),鼻塞有中等程度的益处,流涕有小的益处(中等质量证据)。鼻出血的风险增加(高质量证据),但这些数据包括所有严重程度水平;少量血丝可能对患者来说不是主要问题。尚不清楚局部刺激风险是否存在差异(低质量证据)。
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