Evidence for immunosuppression in lung transplantation

Historically, most lung transplant recipients have received triple-drug maintenance immunosuppression consisting of a calcineurin inhibitor, azathioprine, and prednisolone. The introduction of mycophenolate mofetil, mammalian target of rapamycin (mTOR) inhibitors, and antibody-based induction therapy has broadened immunosuppressive options. The purpose of this review is to summarize the evidence for immunosuppressive regimens in the prevention and treatment of lung allograft rejection.

In clinical practice there has been a shift towards the de-novo use of more potent immunosuppressive regimens incorporating tacrolimus and mycophenolate post-transplant. The available evidence, however, suggests that such protocols do not lessen the risk of development of chronic allograft rejection [bronchiolitis obliterans syndrome (BOS)] compared with more traditional therapy. The role of antibody-based induction therapy remains controversial, with no survival benefit demonstrated in trials to date. The mTOR inhibitors have marked antifibroproliferative activity and are being rigorously evaluated in large, multicenter, randomized trials focused on the prevention of both acute and chronic lung rejection.

Combination therapy with a calcineurin inhibitor, antimetabolite, and a corticosteroid derivative remains the backbone of lung transplant immunosuppression. Induction therapy (in whatever form) may reduce acute rejection, but does not lower the incidence of chronic rejection or improve survival. New strategies utilizing mTOR inhibitors may herald a more promising era.