Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) may develop in a primary (idiopathic) form, chiefly during middle age, or less commonly in the setting of inhalational exposure, hematologic malignancy, or immunodeficiency. Current research supports the theory that PAP is the result of pathophysiologic mechanisms that impair pulmonary surfactant homeostasis and lung immune function. Clinical symptomatology is variable, ranging from mild progressive dyspnea to respiratory failure. There is a strong association with tobacco use. The predominant computed tomographic feature of PAP is a “crazy-paving” pattern (smoothly thickened septal lines on a background of widespread ground-glass opacity), often with lobular or geographic sparing. The radiologic differential diagnosis of crazy-paving includes pulmonary edema, pneumonia, alveolar hemorrhage, diffuse alveolar damage, and lymphangitic carcinomatosis. Definitive diagnosis is made with lung biopsy or bronchoalveolar lavage specimens that reveal intraalveolar deposits of proteinaceous material, dissolved cholesterol, and eosinophilic globules. Symptomatic treatment includes whole-lung lavage, and multiple procedures may be required. New therapies directed toward the identified defect in immune defense have met with moderate clinical success.