Pulmonary Alveolar Proteinosis

Excerpt

Pulmonary alveolar proteinosis (PAP) was first described in 1958 by Samuel H. Rosen et al. . Since that time, clinicians' understanding of this rare lung disease has improved dramatically. Initial reports of this disease described it as respiratory failure secondary to over-production of surfactant proteins within the alveoli . It was believed to be a consequence of inhaled environmental irritants or infectious agents and was initially called acquired or idiopathic PAP . Practitioners now understand that there are 3 separate pathways to the development of surfactant accumulation within alveoli: congenital, secondary, and autoimmune . All 3 of these pathways result in decreased clearance of surfactant, rather than increased production . Autoimmune PAP is the most common pathophysiologic mechanism accounting for 90% of documented cases . Autoimmune PAP is initiated by immunoglobulin (Ig)-G anti-granulocyte macrophage colony stimulating factor (anti-GM-CSF) antibodies, which decrease functional alveolar macrophages . Secondary PAP lacks anti-GM-CSF antibodies but has decreased functional macrophages secondary to hematological malignancies (myelodysplastic syndrome, chronic myelogenous leukemia, among others) or primary immunodeficiency diseases (common variable immunodeficiency, DiGeorge syndrome, among others) . Congenital PAP is the least common and results from genetic mutations in GM-CSF receptor proteins or surfactant proteins .