Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis
Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis
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DOI：
10.1016/j.rmed.2011.10.019
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发表时间：
2012-02-01
影响因子：
4.3
通讯作者：
Tazawa, Ryushi
中科院分区：
文献类型：
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作者：
Ohashi, Kazumasa;Sato, Atsuyasu;Tazawa, Ryushi
背景：自身免疫性肺泡蛋白沉积症（aPAP）是由肺部粒细胞/巨噬细胞集落刺激因子（GM-CSF）自身抗体引起的。此前，我们报道了 GM-CSF 吸入疗法改善了这些患者的肺泡-动脉氧差和疾病严重程度的血清生物标志物。吸入GM-CSF似乎可以改善肺泡巨噬细胞的功能障碍并促进表面活性剂的清除。然而，治疗对支气管肺泡灌洗液（BALF）成分的影响仍不清楚。目的：了解GM-CSF吸入治疗期间表面活性剂清除率的变化。方法：我们对 19 名 aPAP 患者在 GM-CSF 吸入治疗（ISRCTN18931678，JMA-IIA00013；总剂量 10.5-21 mg，持续时间 12-24 周）前后按照标准化方案从同一支气管获得的 BALF 进行回顾性分析。为了进行评估，参与者被分为两组，肺泡-动脉氧差改善> = 13 mmHg的高反应者（n = 10）和< 13 mmHg的低反应者（n = 9）。结果：治疗期间BALF中的总细胞和肺泡巨噬细胞计数均未增加。然而，高反应者中的总蛋白和表面活性剂蛋白-A (SP-A) 显着降低，但低反应者中则没有，这表明表面活性剂物质的清除与治疗效果相关。在支气管肺泡灌洗液中筛选的94个生物标志物中，我们发现GM-CSF吸入治疗后白细胞介素17和癌抗原125的浓度显着升高。结论：GM-CSF吸入降低了BALF中总蛋白和SP-A的浓度，并增加了改善自身免疫性肺泡蛋白沉积症的肺中白细胞介素17和癌抗原125的浓度。 (C) 2011 Elsevier Ltd. 保留所有权利。
Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear.Objectives: To figure out changes in surfactant clearance during GM-CSF inhalation therapy. Methods: We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference >= 13 mmHg (n = 10) and low responders with that < 13 mmHg (n = 9).Results: Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment.Conclusions: GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. (C) 2011 Elsevier Ltd. All rights reserved.