Koenig Steven M, Murray John J, Wolfe James, Andersen Leslie, Yancey Steve, Prillaman Barbara, Stauffer John, Dorinsky Paul
Division of Pulmonary Medicine and Critical Care, University of Virginia, Hospital Drive, Private Clinics #6590, Charlottesville, VA 22908, USA.
Respir Med. 2008 May;102(5):665-73. doi: 10.1016/j.rmed.2007.12.023. Epub 2008 Mar 6.
Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR.
After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR.
The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037).
This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.
关于生物标志物在常规哮喘管理中指导治疗决策的应用，人们了解甚少。本研究的目的是确定在根据常规临床指标评估（无论是否测量支气管高反应性）进行药物滴定的情况下，在吸入性糖皮质激素（ICS）中添加长效β2受体激动剂（LABA）是否能以总体更低剂量的ICS控制支气管高反应性（BHR）。
经过2周的导入期后，受试者（≥12岁）被随机分为三个治疗组之一。两组遵循BHR治疗策略（基于临床参数[肺功能、哮喘症状和支气管扩张剂使用情况]以及BHR），分别接受丙酸氟替卡松/沙美特罗治疗（FSC(BHR)组）或丙酸氟替卡松治疗（FP(BHR)组）（每组n = 156）。第三组遵循临床治疗算法（仅基于临床参数），接受丙酸氟替卡松治疗（FP(REF)组；n = 154）。所有治疗均通过都保装置给药。根据受试者的病情严重程度分级，每8周根据需要调整治疗剂量，共40周，病情严重程度分级基于哮喘控制的临床指标，无论是否有BHR。
在双盲治疗期间，FSC(BHR)组的每日吸入糖皮质激素（ICS）平均总剂量低于FP(BHR)组，尽管差异无统计学意义（差值为 -42.9 mcg；p = 0.07）。与FP(REF)组相比，FSC(BHR)组的每日ICS平均总剂量更高（差值为85.2 mcg），而FP(BHR)组显著更高（差值为131.2 mcg，p = 0.037）。
本研究表明，对于大多数受试者，当治疗针对临床参数的控制时，BHR得以维持。此外，与沙美特罗同时使用时，存在以更低剂量ICS控制BHR和临床指标的趋势。
