title: Morphometric Analysis of Explant Lungs in Cystic Fibrosis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
authors.forename: Mieke
authors.initials: M
authors.lastname: Boon
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.affiliation: 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bosch
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Elise J
authors.initials: EJ
authors.lastname: Lammertyn
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: John E
authors.initials: JE
authors.lastname: McDonough
authors.affiliation: 3 Department of Pulmonary Radiology, and.
authors.forename: Cindy
authors.initials: C
authors.lastname: Mai
authors.affiliation: 3 Department of Pulmonary Radiology, and.
authors.forename: Johny
authors.initials: J
authors.lastname: Verschakelen
authors.affiliation: 4 Department of Radiology and.
authors.forename: Mariette
authors.initials: M
authors.lastname: Kemner-van de Corput
authors.affiliation: 4 Department of Radiology and.|5 Department of Paediatrics, Respiratory Medicine and Allergology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Harm A W
authors.initials: HA
authors.lastname: Tiddens
authors.affiliation: 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.affiliation: 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
authors.forename: François L
authors.initials: FL
authors.lastname: Vermeulen
authors.affiliation: 6 Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Verbeken
authors.affiliation: 7 Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Joel
authors.initials: J
authors.lastname: Cooper
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.affiliation: 8 University of British Columbia James Hogg Research Centre, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.affiliation: 2 Lung Transplant Unit, Laboratory of Pulmonology, Department of Clinical and Experimental Medicine, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.affiliation: 1 Pediatric Pulmonology and Cystic Fibrosis Unit, Department of Pediatrics.
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000000981:diagnostic imaging* / Q000503:physiopathology; D056151:Airway Remodeling; D001980:Bronchi; D055745:Bronchioles; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging*; D016040:Lung Transplantation; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D009929:Organ Size; D010991:Plethysmography; D011013:Pneumonectomy; D012115:Residual Volume; D013147:Spirometry; D014109:Total Lung Capacity; D014797:Vital Capacity; D055114:X-Ray Microtomography; D055815:Young Adult
keywords: airway obstruction; airway remodeling; cystic fibrosis; micro-CT