학술논문
Morphometric Analysis of Explant Lungs in Cystic Fibrosis
Document Type
Academic Journal
Author
Boon, Mieke; Verleden, Stijn E.; Bosch, Barbara; Lammertyn, Elise J.; McDonough, John E.; Mai, Cindy; Verschakelen, Johny; Kemner-van de Corput, Mariette; Tiddens, Harm A. W.; Proesmans, Marijke; Vermeulen, François L.; Verbeken, Erik K.; Cooper, Joel; Van Raemdonck, Dirk E.; Decramer, Marc; Verleden, Geert M.; Hogg, James C.; Dupont, Lieven J.; Vanaudenaerde, Bart M.; De Boeck, Kris
Source
American Journal of Respiratory and Critical Care Medicine. Mar 01, 2016 193(5):516-526
Subject
Language
English
ISSN
1073-449X
Abstract
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 (interquartile range) number (631 [511-710] vs. 344 [277-349]; P = 0.003) and size of visible airways (cumulative airway diameter 217 cm [209-250] vs. 91 cm [80-105]; P < 0.001) 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 (2.9/ml [2.6-4.4] vs. 5.3/ml [4.8-5.7]; P < 0.001); 49% were obstructed, and the cross-sectional area of the open terminal bronchioles was reduced (0.093 mm [0.084-0.123] vs. 0.179 mm [0.140-0.196]; P < 0.001). 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.