Natural History and Clinical Course

The clinical course of PAP is variable, ranging from spontaneous resolution to death secondary to pneumonia or respiratory failure (1,2,4,11). Spontaneous resolution occurs in 8% to 25% of cases (11,51). The five-year survival in a retrospective analysis of 343 cases of PAP was approximately 75% (11). With the therapeutic use of WLL (discussed below), fatalities are rare now. More recent data suggests a survival rate of close to 100% in the last 10 years (11), compared to 70% prior to the use of WLL (52). 

Patients with PAP are at an increased risk of infections not only with common respiratory pathogens but also opportunistic organisms such as Mycobacterium tuberculosis, Mycobacterium avium-intracellulare (MAI), Aspergillus spp. Pneumocystis carinii, and Nocardia spp. (11,53). Seven cases of lung cancer in patients with iPAP have been reported (54), but whether or not this is a true association is not known. 

Defective clearance of surfactant, mediated by circulating antibodies against GM-CSF, is the cardinal pathogenetic mechanism responsible for iPAP (5,23). AMs in iPAP exhibit defects in chemotaxis, phagocytosis, and phagolysosomal fusion and clearance of surfactant (4,5). 

Pulmonary surfactant, a complex mixture of phospholipids and proteins synthesized and secreted by alveolar type 11 cells, functions to keep alveoli from collapsing during expiration (55). Surfactant is composed of 90% to 95% lipids and 5 to 10% proteins including SP-A, -B, -C, and -D (5,56,57). All four of the SP accumulate within the alveolar spaces in PAP (57). The two hydrophilic SP, A and D, have been the most studied. SP-A and SP-D belong to the coUectin family and play roles in the innate immunity of the lung (55). Pulmonary collectins have antimicrobial effects and display both inflammatory and anti-inflammatory properties (55). In iPAP, AMs exhibit defective clearance of surfactant however. 

Inciting stimuli for PAP are not known. However, a history of exposure to hydrocarbons, chemicals, fiberglass, metals, dusts, or solvents has been elicited in up to 50% of cases (2,4). In animal models, inhalation of dust particles elicits a PAP-Uke syndrome (4). One patient with silicosis, PAP, and circulating GM-CSF antibodies was reported (82). 

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