Abstract
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by progressive accumulation
of pulmonary surfactant. This results in dyspnea, secondary pulmonary and systemic
infection, and in some cases respiratory failure. PAP syndrome occurs in distinct
diseases, classified according to pathogenetic mechanism; these include primary PAP
(due to disruption of granulocyte-macrophage colony-stimulating factor [GM-CSF] signaling),
secondary PAP (due to reduction in alveolar macrophage numbers/functions), and congenital
PAP (due to disruption of surfactant production). In primary PAP, the most common
cause is autoimmune PAP, which accounts for over 90% of all PAP syndrome. The pathogenesis
is driven by reduced GM-CSF-signaling causing abnormal alveolar macrophage function
which subsequently results in impaired alveolar surfactant clearance. Autoimmune PAP
can be accurately diagnosed by serum GM-CSF autoantibody levels and there now exist
other diagnostic tests for rare causes of PAP syndrome. The current standard treatment
is whole lung lavage; however, there is emerging evidence to support the use of novel
therapeutic approaches, including inhaled GM-CSF, immune modulation, gene and cell
therapy, and targeting macrophage cholesterol homeostasis. Furthermore, several innovative
approaches to monitor disease severity and response to therapy have recently been
developed.
Keywords
pulmonary alveolar proteinosis - surfactant - GM-CSF - whole lung lavage - autoimmune
