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Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults

Authors
Edward D Chan, MD
Talmadge E King, Jr, MD
Section Editor
Kevin R Flaherty, MD, MS
Deputy Editor
Helen Hollingsworth, MD

INTRODUCTION

Pulmonary alveolar proteinosis (PAP), also known as pulmonary alveolar phospholipoproteinosis, is a diffuse lung disease characterized by the accumulation of amorphous, periodic acid-Schiff (PAS)-positive lipoproteinaceous material in the distal air spaces [1,2]. There is little or no lung inflammation, and the underlying lung architecture is preserved. The lipoproteinaceous material is composed principally of surfactant phospholipid and apoproteins.

The etiology, pathogenesis, clinical manifestations, and diagnosis of PAP in adults will be reviewed here. The presentation and management of PAP in children and the treatment and prognosis of PAP in adults are discussed separately. (See "Pulmonary alveolar proteinosis in children" and "Treatment and prognosis of pulmonary alveolar proteinosis in adults".)

DEFINITIONS AND CLASSIFICATION

PAP is caused by a spectrum of disorders that negatively affect production and clearance of surfactant. Three main categories of PAP are recognized (table 1) [2,3]:

Disruption of granulocyte-macrophage colony-stimulating factor signaling (autoimmune and hereditary PAP) – Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates clearance of surfactant by alveolar macrophages. Disorders that disrupt GM-CSF signalling include autoimmune PAP (the most common type of PAP in adults) and hereditary PAP due to recessive variants of the GM-CSF receptor alpha and beta genes (CSF2RA and CSF2RB). Antibodies to GM-CSF neutralize the effect of GM-CSF on alveolar macrophages, while genetic variants in the GM-CSF receptor impair signaling by intact GM-CSF.

Disorders of surfactant production (congenital PAP) – Disorders of surfactant production are traditionally considered congenital PAP. These disorders often present in the neonatal period and encompass a number of genetic variants:

                    
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Literature review current through: Sep 2017. | This topic last updated: Mar 06, 2017.
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