Recurrent pulmonary alveolar proteinosis secondary to agammaglobulinemia

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant derived material in the lung of patients. PAP is rare in children. The patient presented with respiratory failure. In the history she was diagnosed with agammaglobulinemia at 8 months of age and has been treated by IVIG once in a month. She had two pulmonary alveolary proteinosis attacks before. Chest X-ray showed bilateral diffuse infiltrates. Initial diagnosis were pneumonia, ARDS, and lung edema. Whole-lung lavage revealed lipoproteinaceous material similar to surfactant. This findings and high level of LDH was as evaluated pulmonary alveolary proteinosis. She discharged from the hospital without any respiratory complication on the ninth day. This is the first case report recurrent PAP associated with agammaglobulinemia.     

Liquid ventilation in an infant with pulmonary alveolar proteinosis

Partial liquid ventilation (PLV) has been applied in various pulmonary diseases. We describe the use of partial liquid ventilation as a lavage method following normal saline (NS) lavage in an infant with pulmonary alveolar proteinosis (PAP) and severe hypoxemia. A 6 weeks old 3.4 kg former 36 weeks gestation boy on supplemental oxygen was transferred to our NICU with persistent tachypnea, dry cough, and increasing oxygen requirements. A lingular open lung biopsy revealed PAP. He developed progressive respiratory failure requiring ventilatory support, necessitating conventional NS lavage, followed by lung lavage with perflubron (LiquiVent; Alliance Pharmaceutical Corp. and Hoechst Marion Roussel) while on venovenous extracorporeal life support (ECLS). Lung lavage with NS and perflubron yielded minimal cloudy effluent. Gas exchange and pulmonary function deteriorated following NS lavage and attempts to discontinue ECLS were poorly tolerated. In contrast, tidal volume, P_aO₂, and pulmonary compliance increased after PLV, while the (A-a) DO₂ decreased to a point where ECLS was no longer required. Once perflubron was added repeatedly to the ventilator circuit to correct for evaporation over the 4 days of PLV. Cardiovascular status remained stable for several days; however, eventually he required reinitiation of ECLS and more mechanical ventilatory support with each trial off ECLS. He was maintained on high pressures and F_iO₂ without any possibility to wean him from mechanical ventilation. Life support was withdrawn 1 month after admission. The survival from PAP in infants remains dismal, even with total lung NS lavage. While both NS and perflubron lavage in this patient were not effective in removing the proteinaceous alveolar debris, PLV following NS lavage was associated with an improvement in gas exchange and lung compliance. Pediatr Pulmonol. 1998; 26:283–286. © 1998 Wiley-Liss, Inc.     

肺泡蛋白沉积症研究进展

肺泡蛋白沉积症(PAP)是一种肺部少见病,以肺泡腔和细支气管腔沉积PAS染色阳性的不可溶性富磷脂蛋白质物质为特征.可分为因表面活性蛋白或GM-CSF受体基因突变导致的先天性PAP、因GM-CSF抗体阻断了肺泡巨嗟细胞的激活导致的自身免疫性PAP和继发于血液系统疾病或吸入有毒气体导致的继发性PAP.临床表现主要为进行性气促、低氧血症,胸部高分辨率CT主要表现为毛玻璃样高密度影和“疯狂堆砌”改变,支气管肺泡灌洗液PAS染色阳性可确诊.肺泡灌洗治疗有效,GM-CSF替代疗法和针对GM-CSF抗体的治疗是正在研究的治疗方法.     

粒-巨噬细胞集落刺激因子和肺泡蛋白沉积症

肺泡蛋白沉积症(pulmonary alveolar proteinosis,PAP)是一种少见疾病,特征是类肺泡表面活性物质在肺泡内的沉积,关于其发病机制不甚清楚。但是从对缺乏粒-巨噬细胞集落刺激因子(granulocyte-macrophage colony-stimulating factor,GM-CSF)转基因小鼠的研究,以及测得抗GM-CSF抗体,偶然发现了PAP更深入的分子学机制。本文就GM-CSF在PAP发病机制和治疗方面的进展作一综述。     

肺泡蛋白沉着症10例临床分析

目的通过临床病例分析,了解肺泡蛋白沉着症（PAP）的临床和影像学表现,提高诊断水平。方法回顾分析确诊的10例PAP患者的临床资料。结果男8例,女2例,平均年龄46．7岁。病程慢性迁延,主要症状活动后气促,咳嗽等,体征较少。胸部影像表现呈多样化,可归纳为：地图样表现、碎石路样表现、肺实变样表现、肺水肿样表现及肺间质纤维化样表现等。10例经支气管镜肺活检（TBLB）和支气管肺泡灌洗（BALF）明确。结论肺部影像可以充分显示肺泡蛋白沉积症的特点,尽早作TBLB、BALF确诊。     

Membranous nephropathy and pulmonary alveolar proteinosis

A 47-year-old woman with a severe cough and high-grade fever demonstrated proteinuria of 3.2 g/day. Chest radiograph and CT scan revealed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lungs. The serum levels of surfactant A, surfactant D, and KL-6 were increased to 190 ng/ml (normal: 0-43.8), 360 ng/ml (normal: 0-110), and 4850 U/ml (normal: 0-500), respectively. Video-assisted thoracoscopic lung biopsy revealed eosinophilic amorphous material within alveoli and thickened alveolar septa, which is compatible with pulmonary alveolar proteinosis. Kidney biopsy exhibited membranous nephropathy (Stage I-II) accompanied by granular IgG deposition along the glomerular basement membrane. Although the patient refused treatment with granulocyte macrophage colony stimulating factor (GM-CSF) for pulmonary alveolar proteinosis, her proteinuria and the pulmonary lesion gradually diminished and disappeared after one year.     

Secondary pulmonary alveolar proteinosis in hematologic malignancies

Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as “intra-alveolar coagulum”. This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte–macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab.     

肺泡蛋白沉积症的研究进展

肺泡蛋白沉积症（pulmonary alveolar proteinosis，PAP）是一种少见疾病，病因未明，1958年由罗森首先报道，以肺泡及小气道内沉积大量可溶性磷脂蛋白样物质为主要病理特征，过碘酸雪夫（periodic acid Schiff，PAS）反应阳性，临床表现和病程进展多样。从新生儿到老年人均可发病，呈世界性分布，90％以上病例为特发性。近年来，随着对粒细胞-巨噬细胞集落刺激因子（granulocyte macrophage colony stimulating factor，GM-CSF）研究的深入，目前对PAP有了进一步的认识。下面主要就特发性PAP的发病机制、诊断及治疗进展进行综述。     

Defective lung macrophages in pulmonary alveolar proteinosis.

Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment.     

自身免疫性肺泡蛋白沉积症治疗进展

自身免疫性肺泡蛋白沉积症是一种发病率低、临床表现多样的疾病,全肺灌洗是目前治疗的标准方法,但并不是所有的患者治疗有效.本文将对最近出现的针对其发病机制的治疗方法进行综述.     

A case of idiopathic pulmonary alveolar proteinosis

Idiopathic pulmonary alveolar proteinosis (PAP) is a rare disease due to impaired alveolar macrophage function caused by neutralising anti-granulocyte-macrophage colony-stimulating autoantibodies. A nineteen years old male patient was admitted with the complaints of cough, sputum production, dyspnea and fever. There were bilaterally inspiratory fine crackles. The chest radiographs showed bilateral air-space consolidation. On thorax computed tomography; pre-carinal lymph nodes enlargement, ground glass opacities, septal thickening and crazy-paving appearance were determined. Bronchoalveolar lavage was performed and reported was PAP.     

肺泡蛋白沉积症11例临床分析

目的探讨肺泡蛋白沉积症（PAP）的临床特点及治疗方法。方法回顾性分析11例确诊的PAP患者。比较支气管肺泡灌洗（BAL）及全肺灌洗前后血气分析、肺功能及影像学变化。结果11例患者均为隐匿起病,主要症状和体征：咳嗽（11例）,咳痰（11例）,进行性呼吸困难（9例）;8例测定血清乳酸脱氢酶（LDH）的患者中,有4例血清LDH增高;6例患者经肺功能测定,5例表现为限制性通气功能障碍及弥散功能下降,部分患者表现为呼吸衰竭;9例患者的CT表现：7例为双肺弥漫性分布片状磨玻璃样影,1例主要表现为双肺网状纤维条索影,仅有少量片状磨玻璃样,另有1例表现为两肺弥漫分布的斑点状影伴少量网状纤维条索影;肺灌洗后大部分患者临床症状和影像表现有所改善。用力肺活量（FVC）由（67．75±18．21）％提高到（77．06±19．37）％,P〉0．05;DLCO由（53．95±22．11）％提高到（59．98±11．76）％,P〉0．05。结论CT扫描有助于早期诊断PAP,肺灌洗可以改善患者的症状影像表现。     

Therapeutic efficacy of GM-CSF in pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a rare disease characterized by the deposit of lipid-rich proteinaceous material in alveolar spaces. The only effective treatment known to date has been periodic alveolar lavage, a technique that is laborious and requires that the patient be under general anesthesia, with selective endotracheal-bronchial intubation. Complications are not unknown. Progress in our understandint of the pathogenesis of pulmonary alveolar proteinosis has shown it to be related to changes it to be related to changes in alveolar macrophagocytic capability. We describe a patient in whom 8 weeks of subdermal GM-CSF treatment led to significant clinical, radiologic and lung function improvement.     

肺泡蛋白沉积症的研究进展

肺泡蛋白沉积症(pulmonaryalveolarproteinosis,PAP)是一种发病率较低,起病隐匿,确诊困难的肺部疾病,呈特发性或继发于其它疾病。本文就其临床表现、诊断方法及近年来的病因、发病机制研究进展和治疗进展作一综述。