Li Hong-tao, Zhang Tian-tuo, Zhou Hong, Qu Xiu-juan, Wu Wei-ming, Huang Jin
Department of Respiratory Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China.
Respiration. 2007;74(1):33-43. doi: 10.1159/000096023. Epub 2006 Sep 27.
Although results from a few meta-analyses were most uniformly supportive of the beneficial effect of combination therapy on lung function, there were inconsistent results on other endpoints such as asthma exacerbation. Single inhalers of salmeterol and fluticasone propionate have been available, and some studies compared the effect of combination products with increased doses of inhaled corticosteroids (ICSs) on several outcome variables.
We reviewed the studies systematically, providing a quantitative summary estimate on the efficacy and safety measures of the combination products.
We searched databases (Medline and Embase) from January 1997 to December 2005 using 'fluticasone and salmerterol' or 'Seretide' or 'Advair', in combination with 'randomized controlled trial'. The databases of GlaxoSmithKline Clinical Trial Register and Cochrane Controlled Trials Register, or relevant articles were searched for additional studies.
Combination products had a comparatively low, but significant improvement in pulmonary function, with morning peak expiratory flow (PEF), evening PEF and FEV1 increasing by 17.86 liters/min, 15.57 liters/min and 0.09 liter, respectively, compared with increased doses of inhaled corticosteroid (ICSs) over 12 weeks' treatment. But there were no statistically significant differences in other endpoints such as asthma exacerbation, overall withdrawal and drug-related adverse events, with the exception of overall adverse events and symptom free 24 h, which favored combination products.
Thecombination products provided a statistically significant improvement in lung function and in symptoms but provided no significantly increased protection against exacerbation. Unless high doses of ICSs are required, there is insufficient evidence at present to recommend the use of combination products rather than increased moderate doses of ICSs as a first-line treatment for patients uncontrolled on their current doses of ICSs.
尽管一些荟萃分析的结果大多一致支持联合治疗对肺功能的有益作用，但在哮喘加重等其他终点方面结果并不一致。沙美特罗替卡松单吸入器已经上市，一些研究比较了联合制剂与吸入性糖皮质激素（ICS）增加剂量对多个结局变量的影响。
我们系统回顾了这些研究，对联合制剂的疗效和安全性指标进行定量汇总评估。
我们检索了1997年1月至2005年12月的数据库（Medline和Embase），检索词为“氟替卡松和沙美特罗”或“舒利迭”或“信必可都保”，并结合“随机对照试验”。检索了葛兰素史克临床试验注册数据库和Cochrane对照试验注册数据库，或相关文章以寻找其他研究。
在12周的治疗中，与吸入性糖皮质激素（ICS）增加剂量相比，联合制剂在肺功能方面有相对较低但显著的改善，早晨呼气峰值流速（PEF）、晚上PEF和第1秒用力呼气容积（FEV1）分别增加17.86升/分钟、15.57升/分钟和0.09升。但在哮喘加重、总体撤药和药物相关不良事件等其他终点方面，除总体不良事件和24小时无症状这两个有利于联合制剂的指标外，没有统计学显著差异。
联合制剂在肺功能和症状方面有统计学显著改善，但在预防病情加重方面没有显著增加的保护作用。除非需要高剂量的ICS，目前没有足够的证据推荐使用联合制剂而非增加中等剂量的ICS作为当前剂量ICS治疗效果不佳患者的一线治疗方法。
