Head Karen, Chong Lee Yee, Hopkins Claire, Philpott Carl, Schilder Anne G M, Burton Martin J
UK Cochrane Centre, Summertown Pavilion, 18 - 24 Middle Way, Oxford, UK.
Cochrane Database Syst Rev. 2016 Apr 26;4(4):CD011992. doi: 10.1002/14651858.CD011992.pub2.
This review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms.
To assess the effects of a short course of oral corticosteroids as an adjunct ('add-on') therapy in people with chronic rhinosinusitis who are already on standard treatments.
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015.
Randomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids to placebo or no treatment, where all patients were also receiving pharmacological treatment for chronic rhinosinusitis.
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 adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score, and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.
Two trials with a total of 78 participants met the inclusion criteria. Both the populations and the 'standard' treatments differed in the two studies. Oral steroids as an adjunct to intranasal corticosteroids One trial in adults with nasal polyps included 30 participants. All participants used intranasal corticosteroids and were randomised to either short-course oral steroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 21-day treatment course) or no additional treatment. None of the primary outcome measures of interest in this review were reported by the study. There may have been an important reduction in the size of the polyps (measured by the nasal polyps score, a secondary outcome measure) in patients receiving oral steroids and intranasal corticosteroids, compared to intranasal corticosteroids alone (mean difference (MD) -0.46, 95% confidence interval (CI) -0.87 to -0.05; 30 participants; scale 1 to 4) at the end of treatment (21 days). This corresponds to a large effect size, but we are very uncertain about this estimate as we judged the study to be at high risk of bias. Moreover, longer-term data were not available and the other outcomes of interest were not reported. Oral steroids as an adjunct to antibiotics One trial in children (mean age of eight years) without nasal polyps included 48 participants. The trial compared oral corticosteroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 15-day treatment course) with placebo in participants who also received a 30-day course of antibiotics. This study addressed one of the primary outcome measures (disease severity) and one secondary outcome (CT score). For disease severity the four key symptoms used to define chronic rhinosinusitis in children (nasal blockage, nasal discharge, facial pressure, cough) were combined into one score. There was a greater improvement in symptom severity 30 days after the start of treatment in patients who received oral steroids and antibiotics compared with placebo and antibiotics (MD -7.10, 95% CI -9.59 to -4.61; 45 participants; scale 0 to 40). The observed mean difference corresponds to a large effect size. At the same time point there was a difference in CT scan score (MD -2.90, 95% CI -4.91 to -0.89; 45 participants; scale 0 to 24). We assessed the quality of the evidence to be low.There were no data available for the longer term (three months).
AUTHORS' CONCLUSIONS: There might be an improvement in symptom severity, polyps size and condition of the sinuses when assessed using CT scans in patients taking oral corticosteroids when these are used as an adjunct therapy to antibiotics or intranasal corticosteroids, but the quality of the evidence supporting this is low or very low (we are uncertain about the effect estimate; the true effect may be substantially different from the estimate of the effect). It is unclear whether the benefits of oral corticosteroids as an adjunct therapy are sustained beyond the short follow-up period reported (up to 30 days), as no longer-term data were available.There were no data in this review about the adverse effects associated with short courses of oral corticosteroids as an adjunct therapy.More research in this area, particularly research evaluating longer-term outcomes and adverse effects, is required.
本综述是六项Cochrane综述中的一项，旨在探讨慢性鼻窦炎患者的主要药物治疗方案。慢性鼻窦炎是一种常见疾病，涉及鼻腔和鼻窦内衬的炎症。其特征为鼻塞、流涕、面部压迫感/疼痛以及嗅觉丧失。该疾病可伴有或不伴有鼻息肉。口服糖皮质激素用于控制炎症反应并改善症状。
评估短期口服糖皮质激素作为辅助（“附加”）疗法对已接受标准治疗的慢性鼻窦炎患者的疗效。
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7期）；MEDLINE；EMBASE；ClinicalTrials.gov；ICTRP以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。
随机对照试验（RCT），比较短期（最长21天）口服糖皮质激素与安慰剂或不治疗，所有患者同时也接受慢性鼻窦炎的药物治疗。
我们采用了Cochrane期望的标准方法程序。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情绪或行为障碍的不良事件。次要结局包括一般HRQL、内镜鼻息肉评分、计算机断层扫描（CT）扫描评分以及失眠、胃肠道紊乱和骨质疏松的不良事件。我们使用GRADE评估每个结局的证据质量；以斜体表示。
两项共78名参与者的试验符合纳入标准。两项研究中的人群和“标准”治疗均有所不同。口服类固醇作为鼻内糖皮质激素的辅助治疗一项针对有鼻息肉的成年人的试验纳入了30名参与者。所有参与者均使用鼻内糖皮质激素，并随机分为短期口服类固醇组（口服甲泼尼龙，1mg/kg，在21天的治疗过程中逐渐减量）或不进行额外治疗组。该研究未报告本综述感兴趣的任何主要结局指标。与仅使用鼻内糖皮质激素相比，接受口服类固醇和鼻内糖皮质激素治疗的患者在治疗结束时（21天）息肉大小（通过鼻息肉评分测量，为次要结局指标）可能有显著减小（平均差值（MD）-0.46，95%置信区间（CI）-0.87至-0.05；30名参与者；1至4级）。这相当于一个较大的效应量，但由于我们判断该研究存在高偏倚风险，所以对这一估计非常不确定。此外，没有长期数据，且未报告其他感兴趣的结局。口服类固醇作为抗生素的辅助治疗一项针对无鼻息肉的儿童（平均年龄8岁）的试验纳入了48名参与者。该试验将口服糖皮质激素（口服甲泼尼龙，1mg/kg，在15天的治疗过程中逐渐减量）与安慰剂在同时接受30天抗生素治疗的参与者中进行比较。该研究涉及一项主要结局指标（疾病严重程度）和一项次要结局（CT评分）。对于疾病严重程度，用于定义儿童慢性鼻窦炎的四个关键症状（鼻塞、流涕、面部压迫感、咳嗽）合并为一个评分。与接受安慰剂和抗生素治疗的患者相比，接受口服类固醇和抗生素治疗的患者在治疗开始后30天症状严重程度有更大改善（MD -7.10，95%CI -9.59至-4.61；45名参与者；0至40级）。观察到的平均差值相当于一个较大的效应量。在同一时间点，CT扫描评分存在差异（MD -2.90，95%CI -4.91至-0.89；45名参与者；0至24级）。我们评估证据质量为低。没有三个月的长期数据。
当口服糖皮质激素作为抗生素或鼻内糖皮质激素的辅助治疗时，使用CT扫描评估，患者的症状严重程度、息肉大小和鼻窦状况可能有所改善，但支持此结论的证据质量低或非常低（我们对效应估计不确定；真实效应可能与效应估计有很大差异）。目前尚不清楚口服糖皮质激素作为辅助治疗的益处是否能在报告的短期随访期（最长30天）之后持续，因为没有长期数据。本综述中没有关于短期口服糖皮质激素作为辅助治疗相关不良反应的数据。该领域需要更多研究，特别是评估长期结局和不良反应的研究。
