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Semin Respir Crit Care Med 2020; 41(02): 288-298
DOI: 10.1055/s-0039-3402727
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pulmonary Alveolar Proteinosis Syndrome

Alan Kelly
1   Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland
2   Department of Medicine, University College Dublin, Dublin, Ireland
,
Cormac McCarthy
1   Department of Respiratory Medicine, St. Vincent's University Hospital, Dublin, Ireland
2   Department of Medicine, University College Dublin, Dublin, Ireland
› Author Affiliations
Further Information

Publication History

Publication Date:
12 April 2020 (online)

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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
 

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