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 corticosteroids, repeated episodes of acute rejection are limited to a minority of transplant patients. Despite early successful transplantation, many patients developed a disabling and fatal condition called obliterative bronchiolitis. This is currently thought to be a result of chronic rejection. The principal risk factor for the development of obliterative 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 immunosuppressive therapy is needed to prevent this complication. Simply increasing the dosage of cyclosporin or oral corticosteroids results in the major complications of opportunistic infection and renal failure. Targeted 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 transplanted organ is easily accessible to targeted therapy by means of inhalation. Inhaled nebulised corticosteroids have been shown to be effective in preventing obliterative bronchiolitis in patients at risk after heart-lung transplantation. Similarly, inhaled cyclosporin has also been reported to be more effective than oral administration, with substantially lower blood concentrations. Such new approaches to targeting immunosuppressive 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.