PT  - JOURNAL ARTICLE
AU  - Lettieri, Sara
AU  - Bonella, Francesco
AU  - Marando, Vincenzo Alfredo
AU  - Franciosi, Alessandro N
AU  - Corsico, Angelo Guido
AU  - Campo, Ilaria
TI  - Pathogenesis-driven treatment of primary pulmonary alveolar proteinosis
AID  - 10.1183/16000617.0064-2024
DP  - 2024 Jul 01
TA  - European Respiratory Review
PG  - 240064
VI  - 33
IP  - 173
4099  - http://err.ersjournals.com/content/33/173/240064.short
4100  - http://err.ersjournals.com/content/33/173/240064.full
SO  - EUROPEAN RESPIRATORY REVIEW2024 Jul 01; 33
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