• Stijn E Verleden, Dragoş M Vasilescu, Stijn Willems, David Ruttens, Robin Vos, Elly Vandermeulen, Jeroen Hostens, John E McDonough, Erik K Verbeken, Johny Verschakelen, Dirk E Van Raemdonck, Benoît Rondelet, Christiane Knoop, Marc Decramer, Joel Cooper, James C Hogg, Geert M Verleden, and Bart M Vanaudenaerde.
• 1 Leuven Lung Transplant Unit, Katholieke Universiteit Leuven and Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.
• Am. J. Respir. Crit. Care Med. 2014 Feb 1; 189 (3): 292-300.

RationaleThe chronic rejection of lung allografts is attributable to progressive small airway obstruction.ObjectivesTo determine precisely the site and nature of this type of airway obstruction.MethodsLungs from patients with rejected lung allografts treated by a second transplant (n = 7) were compared with unused donor (control) lungs (n = 7) using multidetector computed tomography (MDCT) to determine the percentage of visible airways obstructed in each airway generation, micro-computed tomography (microCT) to visualize the site of obstruction, and histology to determine the nature of this obstruction.Measurements And Main ResultsThe number of airways visible with MDCT was not different between rejected and control lungs. However, 10 ± 7% of observed airways greater than 2 mm in diameter, 50 ± 22% of airways between 1 and 2 mm in diameter, and 73 ± 10% of airways less than 1 mm in diameter were obstructed in the rejected lungs. MicroCT confirmed that the mean lumen diameter of obstructed airways was 647 ± 317 μm but showed no difference in either total number and cross-sectional area of the terminal bronchioles or in alveolar dimensions (mean linear intercept) between groups (P > 0.05). In addition, microCT demonstrated that only segments of the airways are obstructed. Histology confirmed a constrictive form of bronchiolitis caused by expansion of microvascular-rich granulation tissue in some locations and collagen-rich scar tissue in others.ConclusionsChronic lung allograft rejection is associated with a progressive form of constrictive bronchiolitis that targets conducting airways while sparing larger airways as well as terminal bronchioles and the alveolar surface.

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