The histology of subcutaneously implanted donor bronchial rings correlateswith rejection scores of lung allografts in a primate lung transplant model

Background: The diagnosis of acute rejection in lung transplantation genera lly relies on transbronchial biopsies. This invasive procedure may be assoc iated with bronchial bleeding or pneumothorax and may not be feasible in pa tients with severely compromised lung function. The hypothesis of the curre nt study was that histopathological findings of donor bronchial segments im planted into the subcutaneous tissue of lung allograft recipients would pre dict lung tissue rejection scores, thus providing the clinician with an alt ernate source of information; Methods: Unilateral left lung transplantation was performed in 34 cynomolgu s monkeys as part of a drug efficacy study. After completion of the transpl ant procedure, 4 bronchial ring segments of the explanted recipient left lu ng and 4 bronchial ring segments of the non-transplanted right donor lung w ere implanted subcutaneously in the abdominal region. Lung allograft reject ion was evaluated by open lung biopsies of the allograft performed on posto perative (PO) Day 14 and during sacrifice on PO Day 28. At the time of each biopsy, 2 donor and 2 recipient subcutaneous bronchial rings were explante d. Histologic evaluation of the lung tissue samples was performed according to the working formulation of the International Society for Heart and Lung Transplantation. Bronchial rings were independently evaluated by assessing the degree of airway narrowing; percentage of intact epithelial coverage a s well as its specific histology (respiratory ciliated, flattened cuboidal, squamous); presence of lymphocytes, macrophages or spindle cells; and pres ence of peribronchial inflammation, luminal fibrosis, lymphocytic bronchiti s or luminal mucous. Statistical analysis was performed by logistic regress ion. Results: In the recipient bronchial rings, there was no evidence of airway narrowing. There was 98% epithelial coverage, 71% that were respiratory cil iated cells, and there was no inflammation. Donor bronchial rings showed no airway narrowing for monkeys with grade A0 to A2 rejection in tissue biops ies and a maximum narrowing (41.2%) with A4 rejection. Epithelial cell cove rage was similar to 100% with grade A0-A2 and 44 +/- 11% with A4 rejection. Lymphocytic bronchitis was most severe in A4 rejection and minimal in AO t o A2 rejection. By logistic regression analysis, independent predictors of a likelihood of rejection were the degree of airway obliteration, the perce ntage of epithelial cell coverage, the degree of lymphocytic bronchitis and the product of respiratory and flattened cuboidal cell coverage. Conclusions: The current data show that histologic alterations of subcutane ously implanted donor bronchial rings correlate with lung tissue biopsy sco res based on the ISHLT working formulation. Because subcutaneous bronchial rings can be explanted under local anesthesia, they may provide useful info rmation for the diagnosis of acute allograft rejection in patients with imp aired tissue samples may not be feasible.