NEJM:白血病药物伊马替尼在严重高气道反应性哮喘中的应用

2017-05-18 zhangfan MedSci原创

伊马替尼可减少重症哮喘患者高气道反应,降低肥大细胞计数并减少类胰蛋白酶的释放

糖皮质激素治疗无法去除哮喘患者呼吸道中的肥大细胞,可导致患者生活质量差和哮喘控制效果不佳。干细胞因子及其受体KIT是维持肥大细胞的重要因素。近日研究人员开展了一项概念证明试验评价KIT抑制剂伊马替尼在严重哮喘患者中对高气道反应性、严重哮喘生理指标以及气道肥大细胞数和活化程度的影响。

研究人员招募了接受最大剂量激素药物治疗后控制效果不佳的严重高气道反应性哮喘患者,接受为期24周的随机双盲伊马替尼治疗。主要终点是PC20测定的高气道反应性的变化。

共62名患者参与研究,伊马替尼治疗比安慰剂表现出更大程度的降低气道高反应性。6个月时,伊马替尼组可增加PC20量1.73±0.60,而安慰剂组为1.07±0.60(P=0.048)。相比于安慰剂,伊马替尼可更大程度地降低血清类胰蛋白酶水平(减少2.02±2.32 vs. 0.56±1.39 ng/ml,P=0.02)。两组气道肥大细胞计数均下降。伊马替尼组比安慰剂组更容易出现肌肉痉挛和低磷血症不良事件。

伊马替尼可减少重症哮喘患者高气道反应,降低肥大细胞计数并减少类胰蛋白酶的释放。该结果表明KIT相关的肥大细胞在重症哮喘的病理学过程中具有重要作用,有望成为新的药物靶点。

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