Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis
Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis
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DOI：
10.1164/ajrccm.161.4.9906044
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发表时间：
2000-04-01
影响因子：
24.7
通讯作者：
Stoller, JK
中科院分区：
文献类型：
--
作者：
Kavuru, MS;Sullivan, EJ;Stoller, JK
肺泡蛋白沉积症（PAP）是一种罕见的肺部疾病，其特征是在肺泡内积聚脂蛋白物质。最近的研究表明，粒细胞-巨噬细胞集落刺激因子（GM-CSF）可能参与PAP的发病机制。为了扩大这一理解并阐明GM-CSF替代是否会带来益处，我们报告了一项开放标签研究中GM-CSF治疗PAP中度加重的前四名患者的初步结果。所有4例患者均经开肺活检证实为特发性PAP。GM-CSF皮下自给药，每日1次，持续12周（剂量从3至9 μ g/kg/d递增）。通过症状评分、动脉血气测量、肺功能测试和胸片来评估疗效。4例患者中有3例使用GM-CSF后症状、生理和影像学改善。应答者在氧合方面有了充分的改善，从而消除了补充氧的需要，并且一名患者从肺移植的等待名单中被删除。氧合改善直到治疗开始后8至12周才明显。值得注意的是，外周血白细胞计数并未出现预期的增加，这表明PAP缺乏对外源性GM-CSF的造血反应。我们得出的结论是，GM-CSF似乎对一部分成人PAP患者有益，并且可能是治疗该疾病的全肺灌洗的替代方法。
Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of lipoproteinaceous material within the alveoli. Recent data suggest that granulocyte-macrophage colony- stimulating factor (GM-CSF) may be involved in the pathogenesis of PAP. To extend this understanding and clarify whether GM-CSF replacement confers benefit, we report the preliminary results for the first four patients in an open-label study of GM-CSF treatment for moderate exacerbation of PAP. All four patients had idiopathic PAP confirmed by open lung biopsy. Subcutaneous GM-CSF was self-administered once daily for 12 wk (dose escalation from 3 to 9 mu g/kg/d). Response was assessed from symptom scores, arterial blood gas measurements, pulmonary function testing, and chest radiographs. Three of the four patients experienced symptomatic, physiologic, and radiographic improvement with GM-CSF. Responders experienced sufficient improvement in oxygenation as to eliminate the need for supplemental oxygen, and one patient was removed from the waiting list for lung transplantation. Improved oxygenation was not apparent until 8 to 12 wk after the start of therapy. Notably, expected increases in the peripheral white blood cell count did not occur, suggesting lack of a hematopoietic response to exogenous GM-CSF in PAP. We conclude that GM-CSF appears to benefit a subset of patients with adult PAP, and may represent an alternative to whole-lung lavage in treating the disease.