Morphometric analysis of explant lungs in cystic fibrosis

Rationale: After repeated cycles of lung infection and inflammation, patients with cystic fibrosis (CF) evolve to respiratory insufficiency. Although histology and imaging have provided descriptive information, a thorough morphometric analysis of end-stage CF lung disease is lacking.
Objectives: To quantify the involvement of small and large airways in end-stage CF.
Methods: Multidetector computed tomography (MDCT) and micro-CT were applied to 11 air-inflated CF explanted lungs and 7 control lungs to measure, count, and describe the airway and parenchymal abnormalities in end-stage CF lungs. Selected abnormalities were further investigated with thin section histology.
Measurements and Main Results: On MDCT, CF explanted lungs showed an increased median number and size of visible airways compared with controls. Airway obstruction was seen, starting from generation 6 and increasing to 40 to 50% of airways from generation 9 onward. Micro-CT showed that the total number of terminal bronchioles was decreased; 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced. On micro- CT, 41% of the obstructed airways reopened more distally. This remodeling was confirmed on histological analysis. Parenchymal changes were also seen, mostly in a patchy and peribronchiolar distribution.
Conclusions: Extensive changes of dilatation and obstruction in nearly all airway generations were observed in end-stage CF lung disease.