Immunopathological changes in the airways of stable lung transplant recipients

Background - Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation, Endobronchial biopsy (EBB) provides a means of examining transplanted airways, This study aimed to investigate the role of EBB samples in revealing early signals of airway injury. Methods - In 18 stable lung transplant recipients with close to maximal lung function (median FEV1, best after transplantation 100%, interquartile range 98-100%) EBB samples were taken simultaneously with transbronchial biopsy samples and bronchoalveolar lavage (BAL) fluid (median 195 days after transplantation), OCT embedded specimens were snap frozen an all isopentane slurry made with liquid nitrogen and 7 pm sections were stained with monoclonal antibodies using a three stage immunoperoxidase method. Results - Compared with nine non-transplanted control subjects, EBB specimens front the stable transplant group had significantly increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p = 0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median 84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115), There was an increase in CD68 positive cells in the EBB specimens from transplant recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for the difference 1 to 84), CD3, CD4, and CD25 counts were similar in the two groups. EBB findings were not influenced by age, sex, indication for transplant, immunosuppression doses or levels, nor the presence of airway commensals in the BAL fluid. Conclusions - EBB is practicable in a transplant setting and provides information about bronchial inflammatory changes, It is likely that there is ongoing inflammation, possibly rejection mediated, even in healthy lung transplant recipients despite triple immunosuppression.