Pulmonary alveolar proteinosis (PAP) is an extremely rare cause of respiratory failure in the pediatric age group. PAP is characterized by intra-alveolar accumulation of surfactant, namely lipid and proteinaceous material that is periodic acid-Schiff (PAS) positive when visualized on light microscopy. [1, 2] The disease is not associated with inflammation, and lung architecture is typically preserved. The clinical course of PAP varies and ranges from respiratory failure and death to spontaneous resolution. 
Three clinically distinct forms of PAP have been described: autoimmune (primary or idiopathic), secondary, and genetic (congenital). [3, 4, 5] Genetic PAP is seen more commonly in children, while adult forms are usually autoimmune. [1, 3, 6, 7, 8] The 3 distinct types of PAP differ in respect to etiology, clinical course, therapy, and outcome. [1, 9, 10]
The alveolar airspaces are filled with a dense proteinaceous-lipid fluid mix, which is thought to occur secondary to impaired clearance of surfactant by alveolar macrophages. [7, 11, 12] Surfactant production, secretion, and reuptake are normal, while surfactant catabolism in alveolar macrophages is impaired.  This surfactant-derived alveolar fluid may cause increased work of breathing, a diminished surface area for gas diffusion, and, ultimately, respiratory failure.  The pulmonary interstitium and airways are relatively spared.
Secondary iatrogenic lung damage may occur in the congenital form as a consequence of the required high levels of ventilator support and high-inspired oxygen concentrations. [14, 15] Pulmonary macrophage dysfunction occurs, resulting in increased risk of superinfection [13, 16, 17]
PAP is extremely rare. In a 2002 report, at least 410 cases in the literature were identified.  The estimated annual incidence was 0.36, and the prevalence was 3.76 cases per million population worldwide.
A 2002 French retrospective study reported 41 patients, while a 2008 Japanese study reported 248 patients. 
In a retrospective analysis of 343 cases of acquired pulmonary alveolar proteinosis, the 5-year survival rate was 75%.  The same retrospective analysis estimated the 5-year survival rate for children younger than 5 years to be 14% ±13%, with only one of 7 young children surviving beyond 10 months. Children with late-onset disease appear to have the best likelihood for survival, but they generally require treatment with repeated lung lavage. 
Many children have prolonged oxygen dependence and other symptoms of respiratory compromise, including dyspnea, chronic cough, and failure to gain weight in the absence of recurrent PAP. 
No race predilection is reported in children or adults.
No male predominance is observed among nonsmokers with PAP; this observation suggests that the overall male predominance is secondary to a more common use of tobacco by men than by women. 
The age distribution of PAP in children is unknown.
What would you like to print?