Autoimmune Pulmonary Alveolar Proteinosis: A Review of Pathogenesis and Emerging Therapies

Autoimmune pulmonary alveolar proteinosis is a heterogenous clinical syndrome of disordered surfactant clearance due to a dysfunctional granulocyte–macrophage colony-stimulating factor signaling axis in the setting of polyclonal autoantibody generation. Recent advancements identifying key mechanistic drivers of this disease have been made. This clinical review summarizes current knowledge of autoimmune pulmonary alveolar proteinosis with an emphasis on contemporary findings on pathogenesis and emerging therapies.

A disturbed granulocyte–macrophage colony-stimulating factor signaling axis leads to downstream dysregulation of cholesterol export within alveolar macrophages. Accumulation of cholesterol impedes surfactant clearance and propagates the syndrome’s disease process.

Whole lung lavage therapy is an invasive procedure performed under general anesthesia which remains the standard of care for autoimmune pulmonary alveolar proteinosis. Augmentation of the defective signaling axis with recombinant human granulocyte-macrophage colony-stimulating factor is a promising treatment modality.