Pulmonary Alveolar Proteinosis

Abstract

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.

Spontaneous Pulmonary Alveolar Proteinosis in Captive “Moustached Tamarins” (Saguinus mystax)

“…10,22 More than 90% of all cases of PAP are classified as a primary acquired disorder of unknown etiology. 7,14,21,26 Recently, investigators have proposed to classify the idiopathic form as autoimmune due to the finding of increased serum values of autoantibodies against granulocyte macrophage-colony stimulating factor (GM-CSF). 3,13,21,25 GM-CSF, is a potent stimulator of myeloid hematopoiesis, 13 and is necessary for the terminal differentiation and function of alveolar macrophages, 3,23 which are responsible for clearance of surfactant from alveoli.…”

“…3,7,10,25 It was believed that the mechanism of development of secondary PAP was unrelated to autoantibodies against GM-CSF but recently two cases were reported in which people had elevated titers of autoantibodies against GM-CSF after exposure to industrial dust inhalation. 5,14 …”

“…19 PAP is characterized by the abnormal accumulation of surfactant in alveolar spaces without the presence of inflammatory cells, 7,19,21,25 and the consequent interference with gas exchange. This eosinophilic, PAS-positive accumulation is due to impaired function of alveolar macrophages.…”

“…This eosinophilic, PAS-positive accumulation is due to impaired function of alveolar macrophages. 3,7,12,19,21,25 The etiology of the disease appears to be multifactorial and has been classified in three forms: acquired, secondary, and congenital. 3,7,21,25 The disease presentation varies from subclinical to respiratory failure and death.…”

Pulmonary alveolar proteinosis: time to shift?

“…The extension of the infiltrates in most patients is disproportionate to symptom perception that is usually mild or even absent: 'clinicoradiologic discrepancy'. Reticular or reticulonodular pattern, as well as airspace consolidation with air bronchograms may also be observed in some patients [120]. The computed tomographic appearance seems even more characteristic showing the so-called 'crazypaving' pattern, a network of septal lines of the dimensions of the secondary pulmonary lobule upon a 'ground-glass' background (FIGURE 2).…”