A Rare Case of Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare surfactant‑clearance disorder most often driven by neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). This leads to accumulation of surfactant in the alveolar spaces, with a symptom spectrum ranging from mild, indolent symptoms to life-threatening respiratory failure. A 50‑year‑old female marathon runner with no smoking history presented with a two-month history of progressively worsening exertional dyspnea and cough. High‑resolution computed tomography (HRCT) showed bilateral peripheral and basal ground‑glass opacities with interlobular septal thickening, producing a "crazy‑paving" pattern. Bronchoalveolar lavage was nondiagnostic; therefore, video‑assisted thoracoscopic surgery (VATS) was performed. Wedge biopsy demonstrated alveolar periodic acid‑Schiff-positive material, and serum GM-CSF autoantibody concentration was 49.9 µg/mL (reference < 3 µg/mL), confirming autoimmune PAP. Whole lung lavage (WLL) yielded transient clinical and radiographic improvement, but relapse occurred within three months, with diffusing capacity of the lungs for carbon monoxide (DLCO) falling to 36% predicted. Daily subcutaneous followed by inhaled recombinant GM-CSF (sargramostim 5 µg/kg) provided lasting symptom relief, reduced ground-glass lung infiltrates, and improved DLCO to 65% of predicted. PAP should be suspected in progressive respiratory failure with typical imaging findings, particularly when no secondary cause is identified. For patients who do not respond to WLL or recombinant GM-CSF, further studies are needed to define the best treatment approach.