Induction 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
One of the major accomplishments of the first successful lung transplantation in 1963 was the prevention of allograft rejection by using azathioprine, prednisone, and Cobalt-60 irradiation to suppress the recipient immune system . Since then, great progress has been made in developing immunosuppression regimens to prevent acute and chronic rejection (bronchiolitis obliterans syndrome) of the lung allograft and to reduce the risk of opportunistic infection, a major side effect of immunosuppression.
The protocols for immunosuppressive therapy following lung transplantation can be divided into three general categories: induction, maintenance, and treatment of rejection. Strategies for induction of immunosuppression in the lung transplant recipient will be reviewed here. Maintenance immunosuppression, the immunology of solid organ transplantation, and the diagnosis and treatment of acute and chronic lung transplant rejection are discussed separately. (See "Maintenance immunosuppression following lung transplantation" and "Transplantation immunobiology" and "Evaluation and treatment of acute lung transplant rejection" and "Chronic lung transplant rejection: Bronchiolitis obliterans".)
Three general principles govern immunosuppressive therapy following lung transplantation.
●The first principle is that immune reactivity and the tendency toward graft rejection are highest in the first 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.
●The second principle is that using low doses of several drugs with non-overlapping toxicities is preferable to higher (and more toxic) doses of fewer drugs whenever feasible. Combination regimens also help to block the many components of the complex immunological cascade that leads to allograft rejection.
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- GENERAL PRINCIPLES
- INDUCTION THERAPY
- Indications and contraindications
- Induction agents
- - Basiliximab/daclizumab
- - Alemtuzumab
- - Anti-thymocyte globulin
- - Muromonab-CD3
- Efficacy of induction therapy
- - Effect on survival
- - Effect on rejection
- Choosing an agent
- PREVENTION OF OPPORTUNISTIC INFECTION
- FUTURE DIRECTIONS
- SUMMARY AND RECOMMENDATIONS