Autoimmune pulmonary alveolar proteinosis

Autoimmune pulmonary alveolar proteinosis (aPAP), also known as primary acquired pulmonary alveolar proteinosis or idiopathic PAP, is a rare lung disorder in which a lipoproteinaceous material — composed primarily of surfactant proteins and lipids — accumulates within the alveoli (tiny air sacs of the lungs), impairing gas exchange. This form accounts for approximately 90% of all pulmonary alveolar proteinosis cases. The disease is caused by the production of autoantibodies (specifically anti-granulocyte-macrophage colony-stimulating factor [anti-GM-CSF] antibodies) that neutralize GM-CSF, a cytokine essential for the maturation and function of alveolar macrophages. Without functional macrophages to clear surfactant, the material progressively fills the alveoli. Key symptoms include progressive exertional dyspnea (shortness of breath with activity), nonproductive cough, fatigue, and in some cases, low-grade fever and weight loss. As the disease advances, patients may develop hypoxemia (low blood oxygen levels) and, in severe cases, respiratory failure. Chest imaging typically reveals bilateral, diffuse ground-glass opacities with a characteristic "crazy paving" pattern on high-resolution CT scan. Patients with aPAP are also at increased risk of secondary pulmonary infections, including opportunistic infections with organisms such as Nocardia and Mycobacterium. The standard treatment for symptomatic autoimmune PAP is whole lung lavage (WLL), a procedure in which one lung at a time is physically washed out under general anesthesia to remove the accumulated surfactant material. WLL often provides significant symptomatic relief, though repeated procedures may be necessary. Emerging therapies include inhaled recombinant GM-CSF supplementation, which aims to restore alveolar macrophage function, and rituximab, a monoclonal antibody targeting B cells to reduce autoantibody production. Some patients experience spontaneous remission, while others follow a chronic relapsing course. The overall prognosis has improved significantly with modern management, and disease-related mortality is relatively low with appropriate treatment.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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