Distinct Airway Involvement in Subtypes of End-Stage Fibrotic Pulmonary Sarcoidosis

Abstract

Sarcoidosis is a systemic granulomatous disease that in most cases affects the lung. Pulmonary fibrotic sarcoidosis is clinically, radiologically and pathologically a heterogeneous condition. Although there is substantial indirect evidence of small airway involvement, direct evidence is currently lacking. to investigate the role of the (small) airways in fibrotic sarcoidosis. and methods: Airway morphology was investigated in 7 explant lungs with end-stage fibrotic sarcoidosis using a combination of CT (large airways), microCT (small airways) and histology and compared to 7 unused donor lungs as controls with specific attention for different radiologically defined sarcoidosis subtypes. Patients with central bronchial distortion (n=3), diffuse bronchiectasis (n=3) and UIP pattern (n=1) were identified based on CT scan, showing respectively a decrease and narrowing of large airways, a similar airway number and increased airway diameter of more distal airways or an increase in airway number and airway diameter compared to controls. The number of terminal bronchioles/mL and total number of terminal bronchioles were decreased in all forms of fibrotic sarcoidosis. Interestingly, the number of terminal bronchioles was inversely correlated with the degree of fibrosis. Furthermore, we identified granulomatous remodeling as a cause of small airway loss using serial microCT and histology. The large airways are differentially involved in subtypes of sarcoidosis, but the terminal bronchioles are universally lost. This suggests that small airway loss forms an important aspect in the pathophysiology of fibrotic pulmonary sarcoidosis.