Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis
Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis
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DOI：
10.1164/ajrccm.163.2.2003146
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发表时间：
2001-02-01
影响因子：
24.7
通讯作者：
Dunn, AR
中科院分区：
文献类型：
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作者：
Seymour, JF;Presneill, JJ;Dunn, AR
肺泡蛋白沉积症（AP）的特征是表面活性物质过度积聚，大多数病例的病因不明。AP的标准治疗是全肺灌洗，这可能无法纠正潜在的缺陷。由于造血细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）是正常的表面活性物质稳态所必需的，我们评估了CM-CSF在特发性AP患者中的治疗活性。14名患者接受5 μ g/kg/d CM-CSF治疗6 - 12周，并连续监测肺泡-动脉氧梯度（[A-a]Do（2））、一氧化碳弥散量、计算机断层扫描和运动试验。对5 μ g/kg/d CM-CSF无反应的患者进行逐步剂量递增，有反应的患者在疾病复发时重新治疗。测定储存的治疗前血清中的CM-CSF中和自身抗体。根据前瞻性标准，14例患者中有5例对5 mug/kg/d GM-CSF有反应，4例患者中有1例在剂量递增（20 mug/kg/d）后有反应。总体缓解率为43%（[A-a]Do（2）平均改善= 23.2 mm Hg）。缓解持续时间的中位数为39周，并且在重新治疗后可以重现。CM-CSF耐受性良好，未观察到晚期毒性。预测缓解的唯一治疗相关因素是CM-CSF诱导的嗜酸性粒细胞增多（p = 0.01）。每12例受试者的治疗前血清中存在GM-CSF中和自身抗体。我们得出结论，GM-CSF对特发性AP具有治疗活性，为全肺灌洗提供了一种潜在的替代方法。
Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of CM-CSF in patients with idiopathic AP. Fourteen patients received 5 mug/kg/d CM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]Do(2)), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 mug/kg/d CM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for CM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 mug/kg/d GM-CSF, and one of four patients responded after dose escalation (20 mug/kg/d). The overall response rate was 43% (mean improvement in [A-a]Do(2) = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. CM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was CM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM-CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.