Milan Stephen J, Hart Anna, Wilkinson Mark
Population Health Sciences and Education, St George's University of London, London, UK.
Cochrane Database Syst Rev. 2013 Oct 23;2013(10):CD010391. doi: 10.1002/14651858.CD010391.pub2.
Dietary antioxidants, such as vitamin C, in the epithelial lining and lining fluids of the lung may be beneficial in the reduction of oxidative damage (Arab 2002). They may therefore be of benefit in reducing symptoms of inflammatory airway conditions such as asthma, and may also be beneficial in reducing exercise-induced bronchoconstriction, which is a well-recognised feature of asthma and is considered a marker of airways inflammation. However, the association between dietary antioxidants and asthma severity or exercise-induced bronchoconstriction is not fully understood.
To examine the effects of vitamin C supplementation on exacerbations and health-related quality of life (HRQL) in adults and children with asthma or exercise-induced bronchoconstriction compared to placebo or no vitamin C.
We identified trials from the Cochrane Airways Group's Specialised Register (CAGR). The Register contains trial reports identified through systematic searches of a number of bibliographic databases, and handsearching of journals and meeting abstracts. We also searched trial registry websites. The searches were conducted in December 2012.
We included randomised controlled trials (RCTs). We included both adults and children with a diagnosis of asthma. In separate analyses we considered trials with a diagnosis of exercise-induced bronchoconstriction (or exercise-induced asthma). We included trials comparing vitamin C supplementation with placebo, or vitamin C supplementation with no supplementation. We included trials where the asthma management of both treatment and control groups provided similar background therapy. The primary focus of the review is on daily vitamin C supplementation to prevent exacerbations and improve HRQL. The short-term use of vitamin C at the time of exacerbations or for cold symptoms in people with asthma are outside the scope of this review.
Two review authors independently screened the titles and abstracts of potential studies, and subsequently screened full text study reports for inclusion. We used standard methods expected by The Cochrane Collaboration.
A total of 11 trials with 419 participants met our inclusion criteria. In 10 studies the participants were adults and only one was in children. Reporting of study design was inadequate to determine risk of bias for most of the studies and poor availability of data for our key outcomes may indicate some selective outcome reporting. Four studies were parallel-group and the remainder were cross-over studies. Eight studies included people with asthma and three studies included 40 participants with exercise-induced asthma. Five studies reported results using single-dose regimes prior to bronchial challenges or exercise tests. There was marked heterogeneity in vitamin C dosage regimes used in the selected studies, compounding the difficulties in carrying out meaningful analyses.One study on 201 adults with asthma reported no significant difference in our primary outcome, health-related quality of life (HRQL), and overall the quality of this evidence was low. There were no data available to evaluate the effects of vitamin C supplementation on our other primary outcome, exacerbations in adults. One small study reported data on asthma exacerbations in children and there were no exacerbations in either the vitamin C or placebo groups (very low quality evidence). In another study conducted in 41 adults, exacerbations were not defined according to our criteria and the data were not available in a format suitable for evaluation by our methods. Lung function and symptoms data were contributed by single studies. We rated the quality of this evidence as moderate, but further research is required to assess any clinical implications that may be related to the changes in these parameters. In each of these outcomes there was no significant difference between vitamin C and placebo. No adverse events at all were reported; again this is very low quality evidence.Studies in exercise-induced bronchoconstriction suggested some improvement in lung function measures with vitamin C supplementation, but theses studies were few and very small, with limited data and we judged the quality of the evidence to be low.
AUTHORS' CONCLUSIONS: Currently, evidence is not available to provide a robust assessment on the use of vitamin C in the management of asthma or exercise-induced bronchoconstriction. Further research is very likely to have an important impact on our confidence in the estimates of effect and is likely to change the estimates. There is no indication currently that vitamin C can be recommended as a therapeutic agent in asthma. There was some indication that vitamin C was helpful in exercise-induced breathlessness in terms of lung function and symptoms; however, as these findings were provided only by small studies they are inconclusive. Most published studies to date are too small and inconsistent to provide guidance. Well-designed trials with good quality clinical endpoints, such as exacerbation rates and health-related quality of life scores, are required.
肺部上皮衬里和衬里液中的膳食抗氧化剂,如维生素C,可能有助于减少氧化损伤(阿拉伯,2002年)。因此,它们可能有助于减轻哮喘等炎症性气道疾病的症状,也可能有助于减轻运动诱发的支气管收缩,这是哮喘的一个公认特征,被认为是气道炎症的一个标志。然而,膳食抗氧化剂与哮喘严重程度或运动诱发的支气管收缩之间的关联尚未完全明确。
与安慰剂或不补充维生素C相比,研究补充维生素C对哮喘或运动诱发支气管收缩的成人和儿童病情加重及健康相关生活质量(HRQL)的影响。
我们从Cochrane气道组专业注册库(CAGR)中识别试验。该注册库包含通过对多个书目数据库进行系统检索以及对期刊和会议摘要进行手工检索而识别出的试验报告。我们还检索了试验注册网站。检索于2012年12月进行。
我们纳入随机对照试验(RCT)。纳入诊断为哮喘的成人和儿童。在单独分析中,我们考虑诊断为运动诱发支气管收缩(或运动诱发哮喘)的试验。纳入比较补充维生素C与安慰剂,或补充维生素C与不补充的试验。纳入治疗组和对照组的哮喘管理提供相似背景治疗的试验。本综述的主要重点是每日补充维生素C以预防病情加重并改善HRQL。哮喘患者病情加重时或因感冒症状短期使用维生素C不在本综述范围内。
两位综述作者独立筛选潜在研究的标题和摘要,随后筛选全文研究报告以确定是否纳入。我们采用Cochrane协作网期望的标准方法。
共有11项试验、419名参与者符合我们的纳入标准。10项研究的参与者为成人,仅1项为儿童。大多数研究的研究设计报告不足以确定偏倚风险,且我们关键结局的数据可用性差可能表明存在一些选择性结局报告。4项研究为平行组研究,其余为交叉研究。8项研究纳入哮喘患者,3项研究纳入40名运动诱发哮喘患者。5项研究在支气管激发试验或运动试验前使用单剂量方案报告结果。所选研究中使用的维生素C剂量方案存在显著异质性,这增加了进行有意义分析的难度。一项针对201名哮喘成人的研究报告称,我们的主要结局健康相关生活质量(HRQL)无显著差异,总体而言该证据质量低。没有数据可用于评估补充维生素C对我们的另一个主要结局成人病情加重的影响。一项小型研究报告了儿童哮喘病情加重的数据,维生素C组和安慰剂组均无病情加重(证据质量极低)。在另一项针对41名成人的研究中,病情加重未按照我们的标准定义,且数据格式不适合我们的方法进行评估。肺功能和症状数据由单项研究提供。我们将该证据质量评为中等,但需要进一步研究以评估这些参数变化可能相关的任何临床意义。在这些结局中,维生素C与安慰剂之间均无显著差异。未报告任何不良事件;同样,这是证据质量极低。运动诱发支气管收缩的研究表明补充维生素C后肺功能指标有一些改善,但这些研究数量少且规模非常小,数据有限,我们判断证据质量低。
目前,尚无证据对维生素C用于哮喘或运动诱发支气管收缩的管理进行有力评估。进一步研究很可能对我们对效应估计的信心产生重要影响,并可能改变估计值。目前没有迹象表明维生素C可作为哮喘的治疗药物推荐。有一些迹象表明维生素C在肺功能和症状方面对运动诱发的呼吸困难有帮助;然而,由于这些发现仅由小型研究提供,因此尚无定论。迄今为止,大多数已发表的研究规模太小且不一致,无法提供指导。需要设计良好、具有高质量临床终点(如病情加重率和健康相关生活质量评分)的试验。