Morphometric Analysis of Explant Lungs in Cystic Fibrosis

Am J Respir Crit Care Med. 2016 Mar 1;193(5):516-26. doi: 10.1164/rccm.201507-1281OC.


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(2) [0.084-0.123] vs. 0.179 mm(2) [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.

Keywords: airway obstruction; airway remodeling; cystic fibrosis; micro-CT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Airway Obstruction / diagnostic imaging*
  • Airway Obstruction / physiopathology
  • Airway Remodeling*
  • Bronchi
  • Bronchioles
  • Case-Control Studies
  • Cystic Fibrosis / diagnostic imaging*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis / surgery
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / diagnostic imaging*
  • Lung Transplantation*
  • Male
  • Maximal Midexpiratory Flow Rate
  • Middle Aged
  • Multidetector Computed Tomography
  • Organ Size
  • Plethysmography
  • Pneumonectomy
  • Residual Volume
  • Spirometry
  • Total Lung Capacity
  • Vital Capacity
  • X-Ray Microtomography
  • Young Adult