1 Service de Pneumologie.
Am J Respir Crit Care Med. 2015 Jun 1;191(11):1242-9. doi: 10.1164/rccm.201410-1818OC.
Systemic steroids are the standard treatment for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) despite their poor efficacy and disabling side effects.
To evaluate the effectiveness and tolerance of budesonide/formoterol as an alternative treatment for BOS after HSCT.
In this randomized, double-blind, placebo-controlled study, we randomly assigned 32 HSCT recipients with mild/severe BOS to receive budesonide/formoterol or placebo for 6 months. The primary outcome was the change in the FEV1 after 1 month of treatment (M1) compared with the baseline value. Patients were unblinded at M1 if there was no improvement in the FEV1. Those who had initially received placebo were switched to budesonide/formoterol. Intention-to-treat analysis was performed to assess the primary outcome. Additional analyses took scheduled treatment contamination into account.
At M1, the median FEV1 increased by 260 ml in the budesonide/formoterol arm compared with 5 ml in the placebo arm (P = 0.012). The median increases in the FEV1 at M1 relative to the baseline value for the treated and placebo groups were 13 and 0%, respectively (P = 0.019). Twenty-five patients received budesonide/formoterol during the study. The median difference in the FEV1 between the baseline and after 1 month of treatment for these patients was +240 ml (P = 0.0001). The effect of budesonide/formoterol on the FEV1 was maintained in the 13 patients who completed 6 months of treatment.
Budesonide/formoterol administration led to a significant improvement in the FEV1 in patients with mild/severe BOS after allogeneic HSCT. Clinical trial registered with www.clinicaltrials.gov (NCT00624754).
尽管全身皮质类固醇治疗异体造血干细胞移植（HSCT）后闭塞性细支气管炎综合征（BOS）的疗效差且副作用大，但仍是其标准治疗方法。
评估布地奈德/福莫特罗作为异体 HSCT 后 BOS 的替代治疗方法的有效性和耐受性。
在这项随机、双盲、安慰剂对照研究中，我们将 32 例 HSCT 后轻/重度 BOS 患者随机分为布地奈德/福莫特罗或安慰剂组，接受治疗 6 个月。主要结局是治疗 1 个月（M1）时 FEV1 与基线值相比的变化。如果 FEV1 没有改善，患者在 M1 时将揭盲。最初接受安慰剂的患者将转为布地奈德/福莫特罗治疗。采用意向治疗分析评估主要结局。额外分析考虑了计划治疗的污染。
在 M1 时，布地奈德/福莫特罗组的 FEV1 中位数增加 260ml，而安慰剂组仅增加 5ml（P=0.012）。治疗组和安慰剂组在 M1 时的 FEV1 相对于基线值的中位数增加分别为 13%和 0%（P=0.019）。25 例患者在研究期间接受了布地奈德/福莫特罗治疗。这些患者的 FEV1 基线值与治疗后 1 个月的中位数差值为+240ml（P=0.0001）。在完成 6 个月治疗的 13 例患者中，布地奈德/福莫特罗对 FEV1 的作用得以维持。
在异体 HSCT 后轻/重度 BOS 患者中，布地奈德/福莫特罗的使用导致 FEV1 显著改善。该研究已在 www.clinicaltrials.gov 注册（NCT00624754）。
