Pulmonary alveolar proteinosis
Pulmonary alveolar proteinosis
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DOI：
10.1038/s41572-019-0066-3
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发表时间：
2019-03-07
影响因子：
81.5
通讯作者：
McCarthy, Cormac
中科院分区：
文献类型：
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作者：
Trapnell, Bruce C.;Nakata, Koh;McCarthy, Cormac
肺泡蛋白沉积症(PAP)是一种以肺泡表面活性物质积聚和肺泡巨噬细胞功能障碍为特征的综合征。PAP可导致潜伏性进行性呼吸困难、低氧性呼吸衰竭、继发性感染和肺纤维化。PAP可根据发病机制分为不同类型：原发性PAP以粒细胞-巨噬细胞集落刺激因子(GM-CSF)信号中断为特征，可为自身免疫性(由GM-CSF自身抗体水平升高引起)或遗传性(由编码GM-CSF受体亚单位的CSF2RA或CSF2RB突变引起)；继发性PAP由各种潜在疾病引起；先天性PAP由参与表面活性物质产生的基因突变引起。在大多数患者中，发病机制是由于肺泡巨噬细胞依赖GM-CSF的胆固醇清除减少，从而损害了肺泡表面活性物质的清除。在大规模人口研究中，帕金森综合症的流行率至少为每百万人7例，影响所有年龄、族裔和地理位置的男子、妇女和儿童，无论其社会经济地位如何，尽管它在吸烟者中更为普遍。自身免疫性PAP占所有病例的90%。管理的目的是改善症状和生活质量；全肺灌洗有效地清除过多的表面活性物质。新的基于发病机制的疗法正在开发中，目标是GM-CSF信号、免疫调节和胆固醇稳态。
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by the accumulation of alveolar surfactant and dysfunction of alveolar macrophages. PAP results in progressive dyspnoea of insidious onset, hypoxaemic respiratory failure, secondary infections and pulmonary fibrosis. PAP can be classified into different types on the basis of the pathogenetic mechanism: primary PAP is characterized by the disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling and can be autoimmune (caused by elevated levels of GM-CSF autoantibodies) or hereditary (due to mutations in CSF2RA or CSF2RB, encoding GM-CSF receptor subunits); secondary PAP results from various underlying conditions; and congenital PAP is caused by mutations in genes involved in surfactant production. In most patients, pathogenesis is driven by reduced GM-CSF-dependent cholesterol clearance in alveolar macrophages, which impairs alveolar surfactant clearance. PAP has a prevalence of at least 7 cases per million individuals in large population studies and affects men, women and children of all ages, ethnicities and geographical locations irrespective of socioeconomic status, although it is more-prevalent in smokers. Autoimmune PAP accounts for >90% of all cases. Management aims at improving symptoms and quality of life; whole-lung lavage effectively removes excessive surfactant. Novel pathogenesis-based therapies are in development, targeting GM-CSF signalling, immune modulation and cholesterol homeostasis.