Immunosuppression strategies in lung transplantation

Careful pharmacologic manipulation of the host immune system to prevent rejection of the lung allograft remains the cornerstone of management following lung transplantation. is immunologic imperative must in turn be balanced with the need to avoid signifi¬cant infection. The immunosuppressive regimens used and extent of immunosuppression achieved have a critical effect on the infection and rejection pro¬les of individuals undergoing lung transplantation, which in turn affects their long-term survival. As our understanding of the immune system has matured, our ability to manipulate it pharmacologically has evolved. This evolution has in turn provided us with an arsenal of drugs aimed at keeping the host immune system quiescent in an attempt to prevent activation of the immune pathways that ultimately lead to rejection of the lung allograft. The discovery of the ¬first selective immunosuppressive drug, cyclosporine, in 1976 revolutionized solid organ transplantation (SOT) and heralded the progression toward longer-term survival that would allow lung transplantation to evolve from a technically possible procedure with poor long-term outcomes to the established treatment of end-stage lung disease that it is today. Current practices in immunosuppressive regimens vary from institution to institution. This variation is reflected in the International Society of Heart and Lung Transplantation (ISHLT) registry data, which describe the broad diversity of induction and maintenance strategies currently in use.1 Most randomized controlled trials in lung transplantation have involved only small numbers of patients; as a result, practice has also been aided by retrospective case series and expert consensus. In essence, the information from these sources, coupled with local expertise and past experience, is what tends to serve as the basis for the immunosuppressive practices of individual institutions, thus leading to the variations in practices reported to the registry. The pharmacologic management of lung transplant recipients varies according to the time from transplantation and is influenced by the infection-rejection pro¬le of the individual recipient. In general, immunosuppressive regimens during the posttransplant period can be divided as follows: 1. The induction phase: Induction encompasses the augmentation of immunosuppression in the perioperative or early postoperative period by using agents such as polyclonal antilymphocyte preparations, anti-CD52 antibodies, or interleukin-2 receptor (IL-2R) antagonists in an attempt to reduce the initial robust T-cell response against the lung allograft and minimize the incidence of acute cellular rejection with the aim of improving long term outcomes. 2. The maintenance phase: Maintenance therapy involves a combination of agents (usually three) aimed at keeping the host immune system quiescent and preventing rejection while simultaneously avoiding the excessive immune depletion that would make mounting responses to infection impossible. 3. Management of rejection: The precise regimens and algorithms involved in the management of rejection are dependent on the pattern and immunologic pathway underlying the process. They range from augmentation of immunosuppression with pulse methylprednisolone therapy to plasmapheresis and immunoglobulin treatment of antibody-mediated rejection (AMR).