Small airways play role in fibrotic sarcoidosis

Small airways loss appears to be an important aspect in the pathophysiology of fibrotic pulmonary sarcoidosis, researchers concluded in a new Chest study.

“Given that both radiologic and pathologic studies consistently demonstrate the existence of multiple presentations of fibrotic sarcoidosis with a potential differential involvement of the airways, we aimed to perform an in-depth investigation of the role of the airways in lungs of patients with end-stage fibrotic sarcoidosis undergoing lung transplantation using a combination of CT scanning, micro-CT scanning and histopathologic analysis, as used previously in other interstitial lung diseases such as IPF and lymphangioleiomyomatosis,” Stijn E. Verleden, PhD, postdoctoral researcher at the University of Antwerp, Belgium, and colleagues wrote.

Using CT scanning of the large airways, micro-CT scanning of the small airways and histologic examination, researchers evaluated airway morphologic features in seven explant lungs of patients (median age, 60 years) with end-stage fibrotic sarcoidosis who underwent lung transplantation for fibrotic sarcoidosis at the University Hospitals Leuven from 2009 to 2020. The features were compared with those of seven unused donor lungs matched by age, sex and smoking history.

Based on CT scan, the researchers identified three patients with central bronchial distortion, three with diffuse bronchiectasis and one with a usual interstitial pneumonia pattern. Compared with controls, patients with central bronchial distortion had a narrowing and decrease of the large airways, those with diffuse bronchiectasis had a similar airway number and increased distal airway diameter of more distal airways, and the one with the usual interstitial pneumonia pattern had an increase in airway number and diameter, according to the results.

The researchers also reported a decreased number of terminal bronchioles per milliliter and total number of terminal bronchioles in all forms of fibrotic pulmonary sarcoidosis. Number of terminal bronchioles was inversely correlated with the degree of fibrotic sarcoidosis, while the number of terminal bronchioles per milliliter was positively correlated with surface density, the researchers wrote.

In addition, using serial micro-CT scans and histologic examination, the researchers identified granulomatous remodeling was a cause of small airways loss.

“Whether the small airways should be therapeutically targeted further remains questionable because the granulomas seem to be involved in the airway loss,” the researchers wrote. “However, given the severe obstruction, especially in the central bronchial distortion group, bronchial dilation may be of value for this specific subgroup of patients.”

This study is the first to extensively validate different fibrotic sarcoidosis radiologic patterns with a specific focus on the role of airways, according to the researchers.