DEVELOPMENTS IN INHALED IMMUNOSUPPRESSIVE THERAPY FOR THE PREVENTION OF PULMONARY GRAFT-REJECTION

Cyclosporin is the main immunosuppressive treatment for lung and heart -lung transplantation. When combined with azathioprine and oral cortic osteroids, repeated episodes of acute rejection are limited to a minor ity of transplant patients, Despite early successful transplantation, many patients developed a disabling and fatal condition called obliter ative bronchiolitis. This is currently thought to be a result of chron ic rejection, The principal risk factor for the development of obliter ative bronchiolitis is undercontrolled acute rejection in the first 3 months after transplantation. Frequent early acute rejection increases the later risk of death and disability. A new approach to immunosuppr essive therapy is needed to prevent this complication, Simply increasi ng the dosage of cyclosporin or oral corticosteroids results in the ma jor complications of opportunistic infection and renal failure. Target ed immunosuppressive treatment delivered to the transplanted organ may offer certain advantages, since a high topical inhaled dosage should be relatively free from systemic complications, The lung as a transpla nted organ is easily accessible to targeted therapy by means of inhala tion, Inhaled nebulised corticosteroids have been shown to be effectiv e in preventing obliterative bronchiolitis in patients at risk after h eart-lung transplantation. Similarly, inhaled cyclosporin has also bee n reported to be more effective than oral administration, with substan tially lower blood concentrations. Such new approaches to targeting im munosuppressive treatment could have specific advantages in long term therapy of lung and heart-lung transplant recipients. They might also be of use in other types of solid organ transplantation.