Clinical approach for pulmonary alveolar proteinosis in children

In this editorial, we discuss the clinical implications of the article by Zhang et al . Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by excessive surfactant accumulation in the alveoli. It is classified into four categories: Primary, secondary, congenital, and unclassified forms. Primary PAP is caused by the disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor signaling, which is necessary for the clearance of surfactant by alveolar macrophages. It is further divided into autoimmune PAP, caused by anti-GM-CSF antibodies blocking alveolar macrophage activation, and hereditary PAP, resulting from mutations in genes encoding GM-CSF receptors. Secondary PAP develops due to conditions affecting the number or function of alveolar macrophages, such as infections, immunodeficiency, hematological disorders, or exposure to inhaled toxins. Congenital PAP is linked to mutations in genes involved in surfactant protein production. Notably, the causes of PAP differ between children and adults. Diagnostic features include a characteristic "crazy-paving" pattern on high-resolution computed tomography, accompanied by diffuse ground-glass opacities and interlobular septal thickening. The presence of PAP can be identified by the milky appearance of bronchoalveolar lavage fluid and histological evaluation. However, these methods cannot definitively determine the cause of PAP. Whole lung lavage remains the standard treatment, often combined with specific therapies based on the underlying cause.