Pulmonary Alveolar Proteinosis Syndrome

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by the accumulation of surfactant in alveoli and terminal airways resulting in respiratory failure. PAP comprises part of a spectrum of disorders of surfactant homeostasis (clearance and production). The surfactant clearance disorders are caused by disruption of GM-CSF signaling (primary PAP) or by an underlying disease that impairs alveolar macrophage functions including surfactant catabolism (secondary PAP). Primary PAP is related to alveolar macrophage dysfunction due to the disruption of GM-CSF signaling caused by a high serum level of anti-GM-CSF autoantibody (autoimmune PAP) (∼90%) or by the mutations in the GM-CSF receptor genes (hereditary PAP). The surfactant production disorders are caused by mutations in genes required for normal surfactant production. The PAP syndrome can be identified based on history, radiologic and bronchoalveolar lavage and/or histopathological findings. The diagnosis of PAP-causing diseases in secondary PAP requires further studies. Whole lung lavage is the current standard therapy and promising new pharmacologic therapies are currently in development.