RT Journal Article SR Electronic T1 Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis JF European Respiratory Review JO EUROPEAN RESPIRATORY REVIEW FD European Respiratory Society SP 240064 DO 10.1183/16000617.0064-2024 VO 33 IS 173 A1 Lettieri, Sara A1 Bonella, Francesco A1 Marando, Vincenzo Alfredo A1 Franciosi, Alessandro N A1 Corsico, Angelo Guido A1 Campo, Ilaria YR 2024 UL http://err.ersjournals.com/content/33/173/240064.abstract AB Pulmonary alveolar proteinosis (PAP) is a syndrome that results from the accumulation of lipoproteinaceous material in the alveolar space. According to the underlying pathogenetic mechanisms, three different forms have been identified, namely primary, secondary and congenital. Primary PAP is caused by disruption of granulocyte−macrophage colony-stimulating factor (GM-CSF) signalling due to the presence of neutralising autoantibodies (autoimmune PAP) or GM-CSF receptor genetic defects (hereditary PAP), which results in dysfunctional alveolar macrophages with reduced phagocytic clearance of particles, cholesterol and surfactant. The serum level of GM-CSF autoantibody is the only disease-specific biomarker of autoimmune PAP, although it does not correlate with disease severity. In PAP patients with normal serum GM-CSF autoantibody levels, elevated serum GM-CSF levels is highly suspicious for hereditary PAP. Several biomarkers have been correlated with disease severity, although they are not specific for PAP. These include lactate dehydrogenase, cytokeratin 19 fragment 21.1, carcinoembryonic antigen, neuron-specific enolase, surfactant proteins, Krebs von Lungen 6, chitinase-3-like protein 1 and monocyte chemotactic proteins. Finally, increased awareness of the disease mechanisms has led to the development of pathogenesis-based treatments, such as GM-CSF augmentation and cholesterol-targeting therapies.PAP is an ultra-rare syndrome characterised by the accumulation of alveolar surfactant, leading to respiratory failure. WLL is still the standard of care while emerging therapies address GM-CSF augmentation and cholesterol efflux with promising results. https://bit.ly/3yUxY2Y