A case of pulmonary alveolar proteinosis with invasion of macrophages in alveolar interstitial region]

A 24-year-old woman was admitted to our hospital on November 2, 1989 for investigation and treatment of abnormal shadows detected in her routine chest radiograph on July 19, 1989. The chest X-ray film on admission showed diffuse infiltrative shadows in the peripheral regions of the bilateral middle and lower lung fields. In addition centrilobular shadows in the subpleural regions with increases irregular densities were found on chest CT. We therefore suspected pulmonary alveolar proteinosis. Bronchoalveolar lavage from the right middle bronchus and transbronchial lung biopsy of the right upper and lower lobes were performed. Electron microscopic examination of a specimen of bronchoalveolar lavage fluid revealed many multilamellar bodies, characteristic of pulmonary alveolar proteinosis. In addition, proteinaceous material containing multilamellar bodies was observed within the alveolar lumina. We diagnosed this case as pulmonary alveolar proteinosis. Electron microscopy also revealed many macrophages in the alveolar walls, some of which contained a few or numerous multilamellar bodies within the secondary lysosomes. We treated this patient with oral and inhaled Ambroxol, with improvement of her clinical condition.     

Remission of pulmonary alveolar proteinosis during antituberculosis chemotherapy]

The patient was a 32-year-old man in whom pulmonary tuberculosis had occurred 5 years after the presumptive onset of pulmonary alveolar proteinosis. A diagnosis of pulmonary tuberculosis was made by sputum smears positive for acid-fast bacilli. Computer tomography of the chest showed ground glass opacities, consolidation and cavitation. Rifampicin, isoniazid and ethambutol were given daily, and streptomycin three times a week. Serial chest radiographs revealed progressive clearing not only of the new but also of the old lung infiltrates thought to be due to pulmonary alveolar proteinosis. Serum LDH and CEA returned to normal values. This case indicates the possibility of improving pulmonary alveolar proteinosis by tuberculosis infection or antituberculosis therapy.     

A case of silicoproteinosis with pneumothorax]

A 46-year-old man was admitted because of an increasingly severe cough and dyspnea on exertion. For 13 years, he had inhaled sand containing 100% crystalline silica (SiO2). Chest radiographs revealed right pneumothorax and diffuse small nodular and ground-glass opacities in both lungs (especially in the upper lung fields). A chest CT scan disclosed several bullae in both upper lobes, and an open lung biopsy was performed along with resection of these bullae. Subsequently, silicotic nodules containing silica and PAS-positive materials were recognized in the alveolar spaces in the histological findings, and a diagnosis of silicoproteinosis was made. We have reported on this case of silicoproteinosis with pneumothorax which progressed for over one year and which showed unusual radiological findings dissimilar to those of primary pulmonary alveolar proteinosis.     

Pulmonary alveolar proteinosis noted in a patient with thymoma

A 74-year-old woman had general fatigue and mild fever in August 2004. Her chest X-ray showed slight ground glass opacities in the upper and middle lung fields of both lungs. Though she was prescribed antibacterial drugs, the abnormal shadows on chest X-ray did not improve. The chest CT showed ground glass opacities and reticular shadows with thickened alveolar septa (crazy-paving appearance) in both lungs, and a clearly defined mass in the anterior mediastinum. She underwent thymo-thymectomy with wedge resection of the upper lobe of the left lung. Anterior mediastinum tumor was pathologically diagnosed as thymoma. Lung biopsy demonstrated alveoli filled with SP-A positive granular materials, and we diagnosed pulmonary alveolar proteinosis. About 1 month after operation, the shadows on chest CT showed improvement. We think there might be some relationship between thymoma and pulmonary alveolar proteinosis.     

Early stage pulmonary alveolar proteinosis detected by chest CT scan in a medical examination]

We report a case of pulmonary proteinosis detected at an early stage and followed up on chest CT. A 49-year-old man underwent detailed examinations because of abnormal shadows on chest CT taken on a routine medical examination. The chest CT revealed almost symmetrical ground glass opacities (GGOs) in both lungs with thickened alveolar septa. We could not make a definitive diagnosis even with bronchoalveolar lavage and transbronchial lung biopsy, but after about half a year, the GGOs increased. VATS-biopsy demonstrated alveoli filled with PAS-positive granular materials, and we made a diagnosis of pulmonary alveolar proteinosis. This case was found at an early stage and we were then able to follow up the disease.     

肺泡蛋白沉积症诊治进展

归纳肺泡蛋白沉积症的临床特点和影像学表现、病理检查特点,探讨其在肺泡蛋白沉积症诊断中的价值,通过文献复习提高对本病的认识.复习国内外相关文献,观察临床症状、影像学表现在肺灌洗治疗前后的变化.重点对胸部影像学(胸部平片和CT)的结果和特点进行分析,探讨其在肺泡蛋白沉积症诊断中的价值.     

Two cases of pulmonary alveolar proteinosis with increase of serum CEA

Two cases of pulmonary alveolar proteinosis with increased serum CEA were reported. In both cases, the clinical diagnosis of pulmonary alveolar proteinosis was confirmed by transbronchial lung biopsy (TBLB). Immunohistochemical study of the lung biopsy specimen showed that CEA staining was present in the region of alveoli where type II alveolar epithelial cells proliferate. It was suggested that proliferative type II cells produced CEA in pulmonary alveolar proteinosis. The study of cell surface markers in their bronchoalveolar lavage fluid (BALF) revealed increase of CD8 and Leu7 positive cells and decrease of CD4 positive cells. In the case 2, there was significant increase of B lymphocytes marker positive cells. These results suggested that there may be abnormal regulation of both T and B lymphocytes and NK cells, leading to dysfunction of the pulmonary alveolar macrophage in pulmonary alveolar proteinosis.     

Pulmonary alveolar proteinosis and aluminum dust exposure

A 44-yr-old male presented with shortness of breath, diffuse X-ray infiltrates, and physiologic evidence of a restrictive lung disease. Biopsy revealed pulmonary alveolar proteinosis. The patient had worked for the previous 6 yr as an aluminum rail grinder in a very dusty environment. Analysis of his lung tissue revealed greater than 300 X 10(6) particles of aluminum/g dry lung; all of the particles appeared as spheres of less than 1 mu diameter. We believe that this case represents an example of pulmonary alveolar proteinosis induced by inhalation of aluminum particles; this finding confirms animal studies which suggest that proteinosis can be produced by very large doses of many types of finely divided mineral dust.     

Clinical study of three myelodysplastic syndrome (MDS) patients with BOOP-like pulmonary disease]

Three cases of myelodysplastic syndrome (MDS) associated with BOOP-like pulmonary disease were reported. They were diagnosed from transbronchial biopsies and clinical features. In two cases, chest radiographs showed ground glass opacities or air space consolidation in both lung fields, and air space consolidation in the right lower lobe in the other case. BALF showed a marked increase of lymphocytes in one case, and organizing pneumonia and alveolitis, and alveolar spaces filled with foamy macrophages were identified histologically. Although no steroid therapy was employed, all three cases improved. However, one patient suffered a relapse 6 months later and thereafter did not respond to corticosteroid therapy.     

Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome]

A 51-year-old man with myelodysplastic syndrome (MDS) was admitted to our hospital because of dyspnea on exertion in December 1999. Chest radiography showed ground-glass shadows in the middle and lower fields of both lungs, and chest computed tomography revealed a typical "crazy paving appearance". The bronchoalveolar lavage fluid was milky in appearance, and so secondary pulmonary alveolar proteinosis associated with MDS was diagnosed. Because there was no need to treat his MDS, we twice performed whole-lung lavage under general anesthesia in January and February 2000. The treatments were effective, and his abnormal chest radiography findings, laboratory data and pulmonary function were normalized. This was a rare case of secondary pulmonary alveolar proteinosis associated with MDS successfully treated with whole-lung lavage.     

Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug

Pulmonary alveolar proteinosis is an uncommon disorder marked by the abnormal accumulation of surfactant within the alveoli. Secondary pulmonary alveolar proteinosis develops in patients who are immunosuppressed, usually with corticosteroids. We present a case of biopsy-proven pulmonary alveolar proteinosis in a patient undergoing therapy with the disease-modifying antirheumatoid arthritis drug leflunomide (Arava; Aventis Pharmaceuticals, Bridgewater, NJ). He was treated with whole lung lavage and discontinuation of leflunomide with good results. This is the first reported association of secondary pulmonary alveolar proteinosis with leflunomide therapy. Pulmonary alveolar proteinosis should be considered in patients with diffuse lung disease that develops while on disease-modifying antirheumatoid arthritis drug therapy.     

A case of pulmonary alveolar microlithiasis showing respiratory failure after 33 years and revealing microliths in bronchoalveolar lavage

A 43-year-old woman was admitted to our hospital because of dyspnea and anorexia. She had hypoxia and cyanosis. The chest roentgenogram revealed dense reticular, partly nodular shadow and emphysematous bullae in both lung fields. An abnormal chest X-ray had been pointed out and pulmonary alveolar microlithiasis had been diagnosed 33 years previously. Bronchoscopy and bronchoalveolar lavage were performed and calcium microliths were seen in the bronchoalveolar lavage fluid smear. Bronchoalveolar lavage appears useful in the diagnosis of pulmonary alveolar microlithiasis. A series of X-ray findings showed development of emphysematous bullae, niveau formation and disappearance of bullae. These changes seem to reveal the progress of her disease from the established stage to the advanced stage. Such a case of pulmonary alveolar microlithiasis over the course of a long period is rare.     

Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome

A 47-year-old man, who had been diagnosed as myelodysplastic syndrome (MDS), complained of a severe cough and a high-grade fever. Chest CT disclosed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lung fields and a mass lesion in the right lower lobe. Pathological findings of the ground-glass opacities and the mass lesion obtained by video-assisted thoracoscopic surgery revealed the accumulation of eosinophilic amorphous material in the alveoli and confirmed the diagnosis of pulmonary alveolar proteinosis (PAP). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in sera were below sensitivity, while the GM-CSF level was elevated in bronchoalveolar lavage fluid. He was diagnosed as secondary PAP associated with MDS.     

Unusual alveolar proteinosis

Pulmonary alveolar proteinosis (PAP), a rare infiltrative disease of unknown aetiology, is characterized by an accumulation of abnormal lung surfactant in the alveoli. The diagnosis is based on the results of the bronchoalveolar lavage (BAL) and sometimes on the lung biopsy. The authors report the case of a 49-year-old woman who was hospitalized for chronic expectoration of the membranes. The chest X-ray revealed alveolar opacities in the lowest part of the right lung. The chest CT scan detected alveolar ground glass opacities with interlobular thickening involving the middle lobe. The BAL was opaque with periodic acid-Schiff stain-positive acellular material. The anatomopathology analysis of the membranes concludes as to the presence of granular eosinophilic material and the absence of neoplasic cells or hydatidous membranes. The diagnosis of PAP was established. Since functional deterioration was not detected, therapy was based on physiotherapy alone. The evolution was favourable, with the disappearance of the symptomatology and the normalisation of the chest X-ray. This observation shows an unusual presentation of PAP based on membrane expectoration and unusual localized lesions.     

Radiological findings in initial pulmonary alveolar proteinosis detected in the post-treatment course of nocardiosis]

Chest CT detected a small localized ground glass opacity in the right upper lung in a 52-year-old woman being treated for nocardiosis. A PAS-stain positive material and elevated surfactant level were confirmed in bronchoalveolar lavage fluid, then a diagnosis of pulmonary alveolar proteinosis was established. In early pulmonary alveolar proteinosis with focal opacity, HRCT can demonstrate the substantial findings of alveolar proteinosis such as a crazy-paving appearance or geographic distribution. We should note that alveolar proteinosis in the early stage is easily overlooked and, in addition, nocardiosis might overlap with alveolar proteinosis.     

A case of pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis complicating chronic myelogenous leukemia]

A 47-year-old woman with chronic myelogenous leukemia was treated with daily busulfan (total dose approximately 500 mg) from December 1988 to January 1990. The disease thereafter remained stable with no evidence of blastic transformation. In February 1990 she developed productive cough and abnormal acinar lung shadows appeared transiently on her chest X-ray. In October 1990, productive cough and linear and abnormal acinar lung shadows reappeared. Expectorated sputa contained acid-fast bacilli (Gaffky 6, 10). Antituberculous therapy was started, which caused severe liver dysfunction. She was admitted to our hospital for evaluation of abnormal lung shadows. Transbronchial lung biopsy revealed pulmonary alveolar proteinosis with thickening of alveolar septa. The alveolar septal thickening was suspected to be a pathological change following pulmonary alveolar proteinosis. Cultures from sputum, cerebrospinal fluid, and bone marrow aspiration specimens revealed atypical mycobacterium (M. avium complex), and the diagnosis of disseminated atypical mycobacteriosis was established. The pathogenesis of the disseminated atypical mycobacteriosis was considered to be superinfection by mycobacteria.     

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.     

Prolonged spontaneous remission in a patient with untreated pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis is a relatively rare, diffuse lung disease for which whole lung bronchopulmonary lavage is an effective treatment. The possibility of spontaneous remission also exists, but few actual cases have been described. This report describes a 56-year-old woman in whom pulmonary alveolar proteinosis was diagnosed 18 years earlier and who had a prolonged spontaneous remission before presenting with disabling symptoms. The possibility of prolonged spontaneous remission, although unusual, needs to be kept in mind when therapeutic decisions are to be made in patients with pulmonary alveolar proteinosis.     

Two cases of pulmonary alveolar proteinosis with increased CEA

Two cases of pulmonary alveolar proteinosis (PAP) with increased CEA were reported. Case 1 was a 62-year-old male with suspected pulmonary fibrosis, who was transferred to our hospital. Laboratory findings on admission revealed 31.3 ng/ml of CEA. Because he had severe dyspnea, lung biopsy was not carried out. His condition gradually deteriorated and he died of respiratory failure. Autopsy revealed he had PAP and no malignancy. Case 2 was a 48 year-old male referred to our hospital because of dyspnea. Serum CEA was 52.8 ng/ml. Microscopic examination of a transbronchial lung biopsy showed PAP. The level of CEA in bronchoalveolar lavage fluid was 151 ng/ml. Unilateral whole lung lavage was performed twice. With the improvement of chest X-ray findings, serum levels of CEA fell to normal level. The molecular weight of CEA in bronchoalveolar lavage fluid was 180,000. Immunochemical staining of CEA in lung revealed nonspecific findings.     

Proteinosis alveolar. Respuesta al tratamiento con factor estimulante de colonias de granulocitos y macrófagos por vía inhalada

Pulmonary alveolar proteinosis is a rare disease characterized by the accumulation of lipoproteinaceous material derived from alveolar surfactant in the alveoli, with a consequent deterioration in gas exchange. Pathogenesis is related to impaired phagocytic function of alveolar macrophages. In recent years, a new treatment for pulmonary alveolar proteinosis—consisting of subcutaneous administration of granulocyte-macrophage colony-stimulating factor (GM-CSF)—has become available. The commonly accepted treatment, and the one to have shown greatest efficacy in pulmonary alveolar proteinosis, is whole lung lavage. Instead of subcutaneous administration, GM-CSF can also be inhaled as an aerosol. This route of administration of GM-CSF is safe and effective in the treatment of pulmonary alveolar proteinosis and represents an alternative to subcutaneous administration or whole lung lavage. We present a patient with pulmonary alveolar proteinosis who was treated with inhaled GM-CSF and describe her clinical and functional outcome after 1 year of treatment.