Characterization of Airway Morphology in Post-infectious versus Post-lung Transplant Bronchiolitis Obliterans.

BACKGROUND

Post-infectious bronchiolitis obliterans (PIBO) may occur following childhood infections. Subsequent dysanaptic lung growth, with differential development of the alveolar compartment over the airways, remains elusive. We performed a morphological characterization of the whole airway tree in PIBO compared to bronchiolitis obliterans syndrome (BOS) after lung transplantation.

METHODS

Lungs from matched PIBO (n=5), BOS (n=5), and non-diseased donors (n=5) were evaluated using ex vivo high-resolution computed tomography (CT) scans followed by three-dimensional (3D)-airway segmentation. Matched lung tissue samples (n=4 locations/lung) were scanned with micro-CT (resolution: 5-10 µm) for 3D terminal bronchiole assessment and histology.

RESULTS

No significant difference in the number of airways per generation (until generation 11) was observed between groups (p=0.86). Airway diameters in PIBO (generations 6-11) and BOS (generations 7-10) were increased compared to controls (overall p=0.018), without significant differences between PIBO and BOS. More obstructed airways were present in BOS versus PIBO (p=0.016), but airway obstructions were larger in PIBO versus BOS (p=0.032). There were significantly fewer terminal bronchioles in PIBO compared to BOS and controls (PIBO: median 2934 terminal bronchioles/lung (IQR:2247-4115), BOS 8424 terminal bronchioles/lung (IQR:6207-10480), controls 10 903 terminal bronchioles/lung (IQR:7583-12 820), p=0.0009), but terminal bronchiole diameters were not significantly different (p=0.37). Obstruction of pre-terminal bronchioles was segmental (i.e., focal with normal distal terminal bronchiole) in BOS, but partly non-focal (non-reopening bronchiole) in PIBO.

CONCLUSIONS

PIBO lungs display an almost threefold decrease in terminal bronchioles compared to BOS, with morphological differences in the type and location of airway obstructions, providing structural evidence supporting dysanaptic lung growth.