IMMUNOSUPPRESSIVE THERAPY FOR LUNG TRANSPLANTATION

Appropriate management of immunosuppressive therapy remains one of the major challenges after lung transplantation. Preoperative therapy con sists of intravenous azathioprine and oral cyclosporin. Early postoper ative therapy consists of standard triple immunosuppression with corti costeroids, azathioprine and either cyclosporin or tacrolimus. Previou sly, corticosteroids were withheld in the first postoperative week to allow for healing of the bronchial anastomosis. However, it has been d emonstrated that corticosteroids can be safely begun immediately posto peratively and this is done in most centres. Recent clinical trials su ggest that the use of tacrolimus instead of cyclosporin may result in fewer episodes of acute cellular rejection and improved graft survival . However, the majority of centres continue to use cyclosporin, as the use of tacrolimus requires special laboratory equipment and experienc e. However, more centres are likely to begin using tacrolimus if data continues to demonstrate improved graft survival. The use of antilymph ocyte antibody preparations in the immediate postoperative period has been found to result in a high incidence of cytomegalovirus infection. Therefore, most centres restrict the use of antilymphocyte antibody p reparations to episodes of recurrent acute cellular rejection or refra ctory chronic rejection. Late postoperative immunosuppression is with azathioprine 1.0 to 2.0 mg/kg, cyclosporin at a dosage to maintain who le blood concentrations of 250 to 350 mu g/L (immunofluorescence assay ) and prednisone (usually 10 mg/day). Treatment of rejection episodes is with corticosteroids (e.g. intravenous methylprednisolone 1 g/day f or 3 days), antilymphocyte antibody preparations or by switching to ta crolimus in patients maintained on cyclosporin. The use of aerosolised immunosuppressants bath to prevent rejection and to decrease systemic toxicity, and the creation of stable chimaeras by simultaneous lung a nd bone marrow transplantation, are under investigation.