Pulmonary alveolar proteinosis
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Pulmonary alveolar proteinosis (PAP) is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy (especially in myeloid leukemia), pulmonary infection, or environmental exposure to dusts or chemicals. Rare familial forms have also been recognized, suggesting a genetic component in some cases.
PAP was first described in 1958 by the physicians Samuel Rosen, Benjamin Castleman, and Averill Liebow. In their case series published in the New England Journal of Medicine on June 7th of that year, they described 27 patients with pathologic evidence of periodic acid Schiff positive material filling the alveoli. This lipid rich material was subsequently recognized to be surfactant. Although the cause of PAP remains obscure, a major breakthrough in the understanding of the etiology of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP. The implications of this finding are still being explored. The disease is more common in males and in tobacco smokers.
The symptoms of PAP include:
Chest x-ray's of affected individuals typically reveal nonspecific alveolar opacities. Diagnosis is generally made by surgical or endoscopic biopsy of the lung, revealing the distinctive pathologic finding.
The clinical course of PAP is unpredictable. Spontaneous remission is recognized; some patients have stable symptoms. Death may occur due to progression of PAP or due to the underlying disease associated with PAP. Individuals with PAP are more vulnerable to infection of the lung by bacteria or fungi.
The standard treatment for PAP is whole-lung lavage, in which sterile fluid is instilled into the lung and then removed, along with the abnormal surfactant material. This is generally effective at ameliorating symptoms, often for prolonged periods. Since the mouse discovery noted above, the use of GM-CSF injections has also been attempted, with variable success. Lung transplantation can be performed in refractory cases.
References
- Rosen SH, Castleman B, and Liebow AA. Pulmonary alveolar proteinosis. New England Journal of Medicine 1958; 258: 1123-1142.
- Seymour JF and Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. American Journal of Respiratory and Critical Care Medicine 2002; 166: 215-235.
- Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis; clinical aspects and current concepts on pathogenesis. Thorax 2000; 55: 67-77.
- Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc. Natl. Acad. Sci. USA 1994; 91: 5592-5596.