Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli and alveolar macrophages due to abnormal surfactant homoeostasis. Identification of the granulocyte-macrophage colony-stimulating factor (GM-CSF) as an indispensable mediator of macrophage maturation and surfactant catabolism was the key discovery leading to the current understanding of the pathogenesis of most forms of PAP. Impaired GM-CSF bioavailability due to anti-GM-CSF autoimmunity is the cause of approximately 90% of adult PAP cases. Abnormal macrophage function due to endogenous or exogenous triggers, GM-CSF receptor defects, and other genetic abnormalities of surfactant production account for the remainder of causes. The usual physiological consequence of PAP is impairment of gas exchange, which can lead to dyspnoea, hypoxaemia, or even respiratory failure and death. Pulmonary fibrosis occurs occasionally in patients with PAP. For patients with moderate to severe disease, whole lung lavage is still the first-line treatment of choice. Supplemental GM-CSF is also useful, but details about indications, choice of agent, and dosing remain unclear. Other therapies, including rituximab, plasmapheresis, and lung transplantation have been described but should be reserved for refractory cases.

中文翻译：

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成人肺泡蛋白沉着症：病理生理学和临床方法。

肺泡肺泡蛋白沉着症（PAP）是一种弥漫性肺部疾病，是由于异常表面活性剂的均流引起的脂蛋白物质在肺泡和肺泡巨噬细胞中的积累而导致的。识别粒细胞-巨噬细胞集落刺激因子（GM-CSF）是巨噬细胞成熟和表面活性剂分解代谢的必不可少的介质是导致目前了解大多数PAP发病机理的关键发现。由于抗GM-CSF自身免疫性导致GM-CSF生物利用度受损是大约90％的成人PAP病例的原因。内源性或外源性触发因素引起的巨噬细胞功能异常，GM-CSF受体缺陷和表面活性剂生产的其他遗传异常是造成其余原因的原因。PAP的常见生理后果是损害气体交换，可能导致呼吸困难，低氧血症，甚至呼吸衰竭和死亡。PAP患者偶尔会发生肺纤维化。对于中度至重度疾病的患者，全肺灌洗仍然是首选的一线治疗方法。补充性GM-CSF也很有用，但有关适应症，​​药物选择和给药的细节仍不清楚。已经描述了其他疗法，包括利妥昔单抗，血浆置换和肺移植，但应保留用于难治性病例。