Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia.
Respir Med. 2010 Aug;104(8):1110-20. doi: 10.1016/j.rmed.2010.04.003. Epub 2010 Apr 28.
Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting beta(2)-agonist (LABA) withdrawal is unclear. Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled. This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration.
Adults using salmeterol/fluticasone combination (SFC) 50/500 microg bd were randomized to SFC 50/500 microg bd or fluticasone propionate (FP) 500 microg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations.
82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV(1) 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 microg, FP:816 microg, p = 0.3), but final dose was lower with SFC (534 microg cf. 724 microg, p = 0.005). ICS dose was reduced by >or=80% in 41% SFC and 15% FP patients. Ambulatory lung function was significantly higher with SFC, but there were no differences between groups in rescue beta(2)-agonist use, clinic spirometry, airway responsiveness, ACQ, sputum eosinophils or FeNO. Baseline airway responsiveness, and pre-reduction blood eosinophils, were significant predictors of mean daily FP dose and dose reduction failure respectively.
Many patients prescribed high-dose combination therapy may be over-treated. Substantial reductions in dose can be achieved with a clinical algorithm, reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity.
This study was commenced before mandatory registration of clinical trials.
哮喘指南建议将吸入性皮质激素（ICS）降至最小有效剂量，但长效β2-激动剂（LABA）的停药时间尚不清楚。最近的 FDA 指南建议一旦哮喘得到良好控制，就停止使用 LABA。这项为期 13 个月的接受高剂量联合治疗的患者双盲研究，调查了在 ICS 剂量减少之前停止使用 LABA 的效果。
使用沙美特罗/氟替卡松（SFC）50/500μg bid 的成年人被随机分配到 SFC 50/500μg bid 或丙酸氟替卡松（FP）500μg bid，随后使用临床算法每 8 周进行一次 ICS 剂量减少。主要结局是平均每日 FP 剂量，包括因加重而使用 ICS。
82 名患者被随机分配。哮喘在基线时得到良好控制，FEV1 平均为预测值的 84.8%，哮喘控制问卷（ACQ）评分为 0.9。平均每日 FP 剂量（SFC：721μg，FP：816μg，p=0.3）无显著差异，但 SFC 的最终剂量较低（534μg 比 724μg，p=0.005）。SFC 组中有 41%的患者和 FP 组中有 15%的患者 ICS 剂量减少了>80%。SFC 组的日间肺功能显著较高，但两组之间的急救β2-激动剂使用、门诊肺功能检查、气道反应性、ACQ、痰嗜酸性粒细胞或 FeNO 无差异。基线气道反应性和预减血嗜酸性粒细胞是平均每日 FP 剂量和剂量减少失败的显著预测因子。
许多接受高剂量联合治疗的患者可能治疗过度。通过临床算法可以实现剂量的大幅减少，与 FP 相比，SFC 可以达到更低的 FP 剂量，而不会失去哮喘控制或增加疾病活动度。
本研究在临床试验强制性注册之前开始。
