Progressive Fibrosing Lung Disease Treated With Nintedanib in a Patient With Long-Standing Autoimmune Pulmonary...

Autoimmune pulmonary alveolar proteinosis (APAP) is caused by impaired surfactant clearance due to neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor. Although whole-lung lavage and inhaled granulocyte-macrophage colony-stimulating factor therapy are established treatment options, pulmonary fibrosis is increasingly recognized as a clinically relevant complication in a subset of patients with APAP. However, the clinical behavior of APAP-associated fibrosing lung disease and the role of antifibrotic therapy remain unclear.

A 54-year-old man with a 15-year history of APAP was referred to our institution. High-resolution computed tomography images obtained before referral showed slow progression of reticulation and traction bronchiectasis, suggesting fibrotic progression rather than recurrence of APAP. At presentation, forced vital capacity (FVC) was 3.31 L (80.0% predicted), and diffusion capacity for carbon monoxide (DL_CO) was preserved. During 6 months of observation, FVC declined to 3.03 L (73.5% predicted), accompanied by worsening dry cough and exertional dyspnea. Nintedanib was initiated for a progressive fibrosing phenotype in the context of APAP. Thereafter, FVC remained relatively stable for 2 years, whereas DL_CO declined during follow-up.

APAP-associated fibrosing lung disease may present with a progressive fibrosing phenotype, but its diagnosis and management remain challenging. This case highlights the importance of distinguishing fibrotic progression from recurrence of intra-alveolar proteinosis.