Pulmonary Alveolar Proteinosis: Pathogenesis, Diagnosis, and Management

Pulmonary alveolar proteinosis (PAP) is an uncommon respiratory disorder caused by an increase in surfactant accumulation in the distal airspaces of the lung. It is a common endpoint of several derangements of the homeostatic mechanisms regulating surfactant metabolism. In adults, the majority of the cases of PAP are of autoimmune etiology and result from an increase in the production of autoantibodies to the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). Less commonly, PAP develops in association with other conditions or is caused by genetic mutations that either disrupt GM-CSF signaling or alter other aspects of surfactant metabolism. Regardless of the etiology, the presenting manifestations are usually nonspecific, and the diagnosis is made from a combination of characteristic chest CT findings and the recovery of eosinophilic, periodic acid-Schiff–positive material from the bronchoscopic lavage or the biopsy. The treatment of PAP has a variable efficacy, but whole lung lavage remains the mainstay of treatment. Newer therapeutic approaches involve the administration of recombinant GM-CSF protein and strategies aimed at reducing levels of anti-GM-CSF antibodies (ie, rituximab and plasmapheresis) in the circulation. In mice, emerging evidence suggests that pulmonary macrophage transplantation might be a viable treatment option for PAP caused by mutations in genes of the GM-CSF receptor. In this review, we detail our current understanding of the PAP pat...
Source: Clinical Pulmonary Medicine - Category: Respiratory Medicine Tags: Interstitial, Inflammatory, & Occupational Lung Disease Source Type: research