Inhaled GM-CSF for Pulmonary Alveolar Proteinosis
Inhaled GM-CSF for Pulmonary Alveolar Proteinosis
复制标题
DOI：
10.1056/nejmoa1816216
复制
发表时间：
2019-09-05
影响因子：
158.5
通讯作者：
Nakata, Koh
中科院分区：
文献类型：
--
作者：
Tazawa, Ryushi;Ueda, Takahiro;Nakata, Koh
肺泡蛋白沉积症是一种以表面活性剂在肺泡内异常积聚为特征的疾病。大多数病例是自身免疫性的，并与抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）的自身抗体相关，该抗体阻止肺泡巨噬细胞清除肺表面活性剂。一项开放标签的2期研究显示，吸入重组人GM-CSF对严重肺泡蛋白沉积症患者有一定的治疗效果；然而，对轻中度疾病患者的疗效尚不清楚。方法：我们对64例自身免疫性肺泡蛋白沉积症患者进行了双盲、安慰剂对照试验，这些患者在呼吸环境空气低于70 mm Hg（或70 mm Hg）时，动脉氧分压（Pao(2)）低于70 mm Hg（或70 mm Hg），每日吸入重组人GM-CSF (sargramostim)，剂量为125 μ g，每天两次，连续7天，每隔一周，连续24周，或安慰剂
Background Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. Methods We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 mu g twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao(2)) while breathing ambient air of less than 70 mm Hg (or