Pulmonary Alveolar Proteinosis Diagnosis and Treatment

Introduction to PAP

Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by accumulation of surfactant proteins and phospholipids in the alveolar spaces, leading to progressive dyspnea, hypoxemia, respiratory failure, and increased risk of secondary infections and pulmonary fibrosis, as reported by the European Respiratory Society 1, 2

PAP results from distinct mechanistic pathways that either impair surfactant clearance or cause abnormal surfactant production, with primary PAP being driven by disruption of GM-CSF signaling, resulting in alveolar macrophage dysfunction and impaired surfactant clearance, according to the European Respiratory Society 1, 3
The prevalence of autoimmune PAP is estimated at 6.7-6.9 per million in the general population, as estimated by the European Respiratory Society 4

Approximately one-third of patients are asymptomatic or minimally symptomatic at presentation, with dyspnea being the most common presenting symptom, as reported by the American College of Chest Physicians 5, 6
Cough that is minimally productive of sputum is common, and some patients present with an initial febrile episode followed by progressive symptoms, according to the American College of Chest Physicians 5, 6

The diagnosis of PAP is based on CT imaging and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis, as recommended by the European Respiratory Society 1, 2, 7
High-resolution CT demonstrates the characteristic "crazy paving" pattern caused by airspace consolidation and thickened interlobular septae, as described by the American College of Chest Physicians 5, 6

Whole lung lavage (WLL) is considered the main treatment for many, but not all, PAP-causing diseases, as reported by the European Respiratory Society 1, 2, 7
Inhaled GM-CSF appears to be a promising option for autoimmune PAP, according to the European Respiratory Society 1, 2, 7
Lung transplantation is considered for progressive respiratory failure, as recommended by the European Respiratory Society and the American College of Chest Physicians 1, 2, 5

The European Respiratory Society considers PAP active in the presence of continuous or progressive symptoms, such as dyspnea, cough, sputum production, chest pain, and weight loss, as well as lung function decline in forced vital capacity (FVC) or diffusing capacity of carbon monoxide (DLco), and hypoxemia measured by arterial blood gas (PaO2, SaO2, AaDO2) 8
Bronchoalveolar lavage (BAL) should be performed as part of the diagnostic work up, including differential cell count, periodic-acid-Schiff (PAS)-staining, and microbiology, with BAL fluid typically reported as milky white, opalescent 8