Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of large amounts of surfactant-derived lipoprotein material within the alveolar spaces. It is primarily caused by the presence of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which impair the ability of alveolar macrophages to clear surfactant.
PAP often has an insidious onset, and 10%-30% of patients are asymptomatic at the time of diagnosis. The most common symptoms are dyspnea accompanied by cough, with occasional expectoration. On chest X-rays, bilateral diffuse infiltrates are typically seen, predominantly around the hilar regions, forming a butterfly pattern. A notable feature is the mismatch between extensive pulmonary infiltrates and relatively mild clinical symptoms.
Characteristic findings on high-resolution computed tomography (HRCT) include:
- Ground-glass opacities sharply demarcated from normal lung tissue, forming a geographic pattern.
- Thickening of interlobular and intralobular septa, creating a polygonal or crazy paving pattern.
The hallmark physiological abnormality is severe hypoxemia caused by intrapulmonary shunting. Bronchoalveolar lavage fluid (BALF) is characteristically milky, thick, and opaque, with sedimentation and layering upon standing. Positive periodic acid-Schiff (PAS) staining of BALF cells or transbronchial lung biopsy (TBLB) tissue confirms the diagnosis.
1/3 of PAP patients may experience spontaneous remission. For those with significant respiratory impairment, whole lung lavage is the first-line and most effective treatment. Some patients respond well to GM-CSF replacement therapy via aerosolized inhalation.