Airway Remodeling in Cystic Fibrosis Is Heterogeneous.

Abstract

RATIONALE+OBJECTIVE/ Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving towards obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis, is still poorly understood. METHOD/ On high-resolution computed tomography (HRCT, 600µm, CF=21, control=6) and micro-computed tomography (µCT, 150µm, CF=3, control=1) scans of inflated explant lungs, AV% (airway/total lung volume) was calculated as marker for bronchiectasis, while airway segmentation was used for generation analysis. Clinical data was retrospectively collected. On µCT (8.5µm) images of lung cores (±2.8cm³), extracted randomly from each lobe (3/lobe), distal airway (DA) diameter, number of airway collapses and open terminal bronchioles (oTB)/mL were analyzed. Morphometric analysis was supplemented with histological analysis of DA collapse. RESULTS/ AV% on HRCT was heterogeneous amongst CF lungs (0.7-4.6%), overlapping with controls (0.4-1.2%). However, the pattern of airway loss on µCT was homogeneous amongst CF lungs and most pronounced from generation 9-16. AV% did not correlate with the number of oTB/mL or FEV1%, which correlated with eachother. Open DA in CF were narrowed compared to DA in controls. On the other hand, collapsed DA in CF showed a varying degree of proximal dilation, with DA diameter correlating with AV%. On histology, collapsed CF DA showed constrictive bronchiolitis. CONCLUSION/ Airway remodeling in end-stage CF is heterogeneous, ranging from minimal bronchiectasis, overlapping with controls, to extensive bronchiectasis with small airway dilation. However, the degree of bronchiectasis is unrelated to functional impairment or amount of small airway loss, underscoring the importance of small airway disease.