Maintenance immunosuppression following lung transplantation
- Sangeeta Bhorade, MD
Sangeeta Bhorade, MD
- Associate Professor of Medicine, Medical Director, Lung Transplant Program
- Northwestern University Feinberg School of Medicine
- Robert M Kotloff, MD
Robert M Kotloff, MD
- Chairman, Department of Pulmonary Medicine
- Respiratory Institute Cleveland Clinic
Maintenance immunosuppressive therapy is administered to all lung transplant recipients to help prevent acute and chronic rejection and the loss of the lung allograft. . Substantial progress has been made in developing immunosuppressive regimens to prevent acute and chronic rejection, while trying to reduce the side effects of immunosuppression . However, despite improvements in immunosuppressive therapy, acute and chronic transplant rejection remain important obstacles to successful lung transplantation.
The protocols for immunosuppressive therapy following lung transplantation can be divided into three general categories: induction, maintenance, and treatment of rejection. Strategies for maintenance of immunosuppression in the lung transplant recipient will be reviewed here. The role of induction agents in immunosuppression, general issues related to lung transplantation, the immunology of sold organ transplantation, and the diagnosis and treatment of acute and chronic lung transplant rejection are discussed separately. (See "Induction immunosuppression following lung transplantation" and "Lung transplantation: An overview" and "Transplantation immunobiology" and "Evaluation and treatment of acute lung transplant rejection" and "Chronic lung transplant rejection: Bronchiolitis obliterans".)
Three general principles underlie immunosuppressive therapy following lung transplantation:
●The first principle is that immune reactivity and the tendency toward graft rejection are highest early (within the first three to six months) after graft implantation and decrease with time. Thus, most regimens employ the highest intensity of immunosuppression immediately after surgery and decrease the intensity of therapy over the first year, eventually settling on the lowest maintenance levels of immunosuppression that are compatible with preventing graft rejection while minimizing drug toxicities.
●The second principle is to use low doses of several drugs with non-overlapping toxicities in preference over higher (and more toxic) doses of fewer drugs whenever feasible. Combination regimens are also better able to block the complex immunological cascade that leads to allograft rejection.
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- GENERAL PRINCIPLES
- AGENTS FOR MAINTENANCE THERAPY
- Calcineurin inhibitors
- - Cyclosporine
- - Tacrolimus
- - Tacrolimus versus cyclosporine
- Nucleotide blocking agents
- - Mycophenolate mofetil
- - Azathioprine
- - Mycophenolate mofetil versus azathioprine
- mTOR inhibitors
- - Sirolimus/everolimus
- - Azathioprine versus sirolimus/everolimus
- MONITORING AND ADJUSTING MAINTENANCE THERAPY
- TREATMENT OF REJECTION
- PREVENTION OF OPPORTUNISTIC INFECTION
- FUTURE DIRECTIONS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS