Clinical characteristics, diagnostic approaches, and management of pulmonary alveolar proteinosis: a scoping review

Pulmonary alveolar proteinosis (PAP) is a rare and heterogeneous lung disease characterized by the accumulation of surfactant-derived lipoproteinaceous material within the alveoli. The clinical features, diagnostic approaches, and management strategies of PAP remain variable, and a comprehensive synthesis of published clinical evidence is lacking. To systematically summarize the current clinical characteristics, diagnostic patterns, and treatment strategies of PAP based on published case reports and clinical studies. A scoping review was conducted by searching multiple databases from inception to 2025. Studies reporting clinical data on PAP were included. Data were extracted and descriptively analyzed in terms of patient characteristics, diagnostic methods, clinical manifestations, auxiliary examinations, treatment approaches, and outcomes. A total of 785 studies involving 7,729 patients were included. Most studies were descriptive (737 studies, 93.9%), and 4,929 male and 2,800 female patients were reported, corresponding to a male-to-female ratio of approximately 1.76:1. Smoking ( n = 3,095) and dust or occupational exposure ( n = 633) were frequently reported. The most commonly reported symptoms were cough ( n = 2,719), exertional dyspnea ( n = 1,396), and sputum production ( n = 1,375). Disease subtype information was available for 1,403 patients, of whom 1,311 (93.4%) had primary PAP; among patients with primary PAP, 1,242 (94.7%) had autoimmune PAP. Laboratory, imaging, pulmonary function, and bronchoscopy data were available for 71.7%, 67.8%, 54.0%, and 21.2% of patients, respectively. Among 2,909 patients with treatment information, WLL was the most frequently reported treatment (1,928 patients, 66.3%), followed by corticosteroid therapy (325, 11.2%) and GM-CSF therapy (232, 8.0%). Current evidence on PAP is dominated by descriptive studies and marked by substantial gaps in diagnostic standardization and disease classification. Clinical manifestations are largely nonspecific, and laboratory and functional assessments are inconsistently reported. Whole lung lavage remains the mainstay of management, but high-quality evidence to guide diagnosis and treatment remains limited.