Pulmonary alveolar proteinosis

Overview
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.

History and pathology
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.

Pathophysiology
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, but significant progress was reported in February, 2007. Researchers in that report discussed the presence of anti-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice.

Epidemiology
The disease is more common in males and in tobacco smokers.

Symptoms
The symptoms of PAP include: Chest x-rays 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.
 * dyspnea (shortness of breath)
 * cough
 * low grade fever
 * weight loss

Histopathological Findings: Pulmonary alveolar proteinosis


Natural History
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.

Treatment
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.