The Site and Nature of Airway Obstruction after Lung Transplantation

Rationale: The chronic rejection of lung allografts is attributable to progressive small airway obstruction. Objectives: To determine precisely the site and nature of this type of airway obstruction. Methods: Lungs 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 Results: The 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 6 317 mm 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. Conclusions: Chronic 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.