Clinical Pearls & Morning Reports
Published March 6, 2019
Pulmonary alveolar proteinosis can be hereditary, secondary, or autoimmune. The autoimmune form is responsible for approximately 90% of cases and results from the development of antibodies that target granulocyte–macrophage colony-stimulating factor (GM-CSF). Read the latest Clinical Problem-Solving article here.
Q: What is the characteristic profile of a patient diagnosed with the autoimmune form of pulmonary alveolar proteinosis?
A: Pulmonary alveolar proteinosis is a rare disorder that is marked by alveolar filling with a lipid-rich proteinaceous material accompanied by large, foamy, alveolar macrophages and relatively few inflammatory cells. The median age at diagnosis is 39 years, and most patients are male, with approximately 70% having a history of smoking.
Q: Is “crazy paving” on chest computed tomography diagnostic of pulmonary alveolar proteinosis?
A: Although crazy paving (diffuse ground-glass opacities with interlobular septal thickening in both lungs) observed on computed tomography is classically associated with pulmonary alveolar proteinosis, in a case series involving 99 patients whose imaging showed crazy paving, only 1 patient had pulmonary alveolar proteinosis, and the most common causes of crazy paving were infection, acute respiratory distress syndrome, and pulmonary edema.
A: Bronchoscopy with bronchoalveolar lavage is the diagnostic test of choice for this condition. A bronchoalveolar lavage with cloudy fluid that is positive on periodic acid–Schiff staining is diagnostic of pulmonary alveolar proteinosis. Clinical testing for serum GM-CSF autoantibodies is commercially available, and the combination of antibody testing and bronchoalveolar lavage obviates the need for lung biopsy in most patients. Although lung biopsy is generally not needed for diagnosis, it is notable for preserved lung architecture with alveolar filling by histologically distinctive coarse and densely eosinophilic material that is positive on periodic acid–Schiff staining.
A: Autoimmune pulmonary alveolar proteinosis is treated with whole-lung lavage, which involves general anesthesia, isolation of the lung with a double-lumen endotracheal tube and single-lung ventilation, and instillation of the other lung with 1-liter aliquots of normal saline followed by chest physiotherapy and drainage of the proteinaceous effluent with the help of postural positioning. In observational studies, whole-lung lavage has been associated with reduced mortality, a substantial reduction in symptoms, and improvement in pulmonary function tests. Subcutaneous or inhaled GM-CSF therapy has been reported in uncontrolled clinical trials to result in improvement in alveolar–arterial oxygen gradient and in quality of life, but long-term effects, including effects on mortality, have not been studied, and data from controlled clinical trials are needed. Therapies considered for refractory disease, on the basis of case reports, include rituximab, therapeutic plasma exchange, and lung transplantation, although the disease can recur in the lung allograft.