Evidence for immunosuppression in lung transplantation.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Hopkins
Peter M
PM
Queensland Centre for Thoracic Transplantation, The Prince Charles Hospital, Chermside, Brisbane, Queensland, Australia. peterwakatipu@hotmail.com
McNeil
Keith
K
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000963:Antimetabolites / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016040:Lung Transplantation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism; D012008:Recurrence; D058570:TOR Serine-Threonine Kinases
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases