title: Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure.
abstract: Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients receiving a redo-transplant as treatment for CLAD. Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were air-inflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology. The MDCT showed reduced lung volume with increased lung weight and density in RAS versus BOS and control (p<0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles (p<0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls (p<0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue. RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue.
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium stijn.verleden@med.kuleuven.be.
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.affiliation: Center for Heart Lung Innovation and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Dragoş M
authors.initials: DM
authors.lastname: Vasilescu
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium Center for Heart Lung Innovation and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: John E
authors.initials: JE
authors.lastname: McDonough
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Ruttens
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Robin
authors.initials: R
authors.lastname: Vos
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Elly
authors.initials: E
authors.lastname: Vandermeulen
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bellon
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Rachel
authors.initials: R
authors.lastname: Geenens
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Verbeken
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Johny
authors.initials: J
authors.lastname: Verschakelen
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.affiliation: Unite de Transplantation Cardiaque et Pulmonaire, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Youri
authors.initials: Y
authors.lastname: Sokolow
authors.affiliation: Unite de Transplantation Cardiaque et Pulmonaire, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christiane
authors.initials: C
authors.lastname: Knoop
authors.affiliation: Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Center for Heart Lung Innovation and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Hogg
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.affiliation: Department of Clinical and Experimental Medicine, Laboratory of Pulmonology, Lung Transplant Unit, KU Leuven - University of Leuven, Leuven, Belgium.
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D008168:Lung / Q000473:pathology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011183:Postoperative Complications; D055031:Primary Graft Dysfunction / Q000503:physiopathology*; D014057:Tomography, X-Ray Computed