Pulmonary alveolar proteinosis

PAP is a rare disease characterized by the accumulation of pulmonary surfactants in the alveoli resulting from decreased clearance and leading to impaired gas exchange.

Defective regulation of pulmonary surfactant in PAP results in surfactant accumulation within alveolar macrophages and alveoli.​​​​​​​​​​​​ It is classified into primary (autoimmune), secondary, and congenital forms.​​​​ In autoimmune PAP, the most common form (90% of cases), GM-CSF autoantibodies inhibit the function of GM-CSF, a cytokine crucial for the differentiation and function of alveolar macrophages. This inhibition leads to defective surfactant catabolism and accumulation of surfactant proteins and lipids within the alveoli. The SFTPB, SFTPC, ABCA3, and TTF1 genes have been implicated in the congenital form of PAP.​​​​​​​​​​​​​​​​.

The incidences of autoimmune and secondary PAP are estimated at 0.2-0.49 cases per million person-years and 0.05 cases per million person-years, respectively.

Risk factors for secondary PAP include hematologic malignancies, lung cancer, glioblastoma, immunodeficiencies, human immunodefociency virus, cytimegalovirus infection, tuberculosis, and inhalation of inorganic dusts.

Clinically, PAP presents with progressive exertional dyspnea, dry cough, and constitutional symptoms such as fever, fatigue, and weight loss. Inspiratory crackles and digital clubbing are often present.

The prognosis of PAP is variable and depends on the underlying cause. Most patients with autoimmune PAP have a disease severity score ≥ 3, and about one-quarter require long-term oxygen therapy and infrequent lavages.