Pulmonary Alveolar Proteinosis
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- Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by accumulation of lipoproteinaceous (surfactant-like) material in the alveolar spaces, leading to impaired gas exchange. Defects in surfactant clearance are thought to be responsible for the disease. There are three recognized categories of PAP (1).
- Primary or idiopathic PAP (90% of cases)
- Primary PAP, which is discussed here, has been found to be associated with anti–granulocyte-macrophage colony-stimulating-factor (GM-CSF) autoantibodies disrupting signaling pathways in macrophage activation (2).
- Secondary PAP (<10% cases)
- Secondary PAP is associated with environmental exposures, immunodeficiency disorders and hematologic disorders (mostly myelodysplastic syndrome), and malignancies (1).
- Congenital PAP (2% of cases)
- Congenital PAP results from several rare gene mutations.
- Whole-lung lavage (WLL), the standard treatment for PAP, has improved prognosis (94% 5-year survival) (3).
- System(s) affected: pulmonary
- Seen worldwide, with median age of onset at 39 years (4)
- Male > female (2 to 3:1) incidence, however, may be confounded by increased smoking rates in males, a known association (3).
Estimated 0.36 per million annually (5)
Estimated 3.7 per million (5)
Etiology and Pathophysiology
- Primary PAP has recently been found to be associated with neutralizing anti–GM-CSF autoantibodies causing impaired functioning of alveolar macrophages, resulting in disruption in surfactant homeostasis (6). Surfactant accumulates in alveoli due to reduced clearance.
- Primary PAP: autoimmune
- No genetic predilection in primary or secondary PAP
- Congenital PAP mostly transmitted in autosomal-recessive pattern (1)
- Association between tobacco smoke exposure and primary PAP (3)
- Exposure to environmental dusts, specifically silica, aluminum, cement, indium, titanium dioxide, nitrogen dioxide, and insulation fibers, has been associated with secondary PAP (2).
- Congenital PAP leads to neonatal respiratory distress syndrome not responsive to surfactant or corticosteroids. It is caused by a mutation in surfactant-protein B or C genes, or GM-CSF receptor β- or α-chain abnormalities (2). Lung transplant is primary therapy for congenital PAP, but prognosis is poor (1)[C].
- Hereditary PAP may present in children and is treated with WLL.
No specific measures for prevention; avoid tobacco smoke exposure.
Commonly Associated Conditions
No conditions commonly associated with primary PAP