Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (
aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized
surfactant is affected. Hereditary PAP is caused by mutations involving the
GM-CSF signaling, particularly in genes for the
GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in
hematologic malignancies, other hematologic disorders, miscellaneous
malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies.
aPAP is related to the production of
GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive 'occupation' of the alveolar spaces by an excessive amount of unprocessed
surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of
infections. Treatment of PAP is based on its etiology. In
aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under
general anesthesia to the inhalation of
GM-CSF 'as needed'.