New immunosuppressive drugs and lung transplantation: last or least?

Lung transplantation has become an accepted treatment modality for end stage lung disease. Traditionally, immunosuppressive maintenance therapy consists of cyclosporin, azathioprine, and prednisolone in kidney and liver transplantation as well as in lung transplantation. Despite the use of these drugs, acute rejection occurs frequently, especially in the first weeks and months after lung transplantation. Although these periods are now almost never life threatening, they are associated with substantial morbidity. Prevalences of acute rejection ranging from 60% to 100% have been reported, depending on whether acute rejection is based on clinical or histological diagnosis. The incidence of acute rejection is far higher after lung transplantation than after any other form of solid organ transplantation. This may be due to the fact that the donor lung contains a substantial amount of immunocompetent tissue and because the lungs are constantly exposed to environmental factors. Bronchiolitis obliterans syndrome (BOS) is the major cause of morbidity and mortality in long term survivors of lung transplantation. 7 It occurs in approximately 30–50% of recipients still alive one year after transplantation and is characterised by progressive airway obstruction, usually in the presence of histological evidence of obliterative bronchiolitis (OB). Once established it is usually refractory to immunosuppressive treatment, thus stressing the importance of preventing this long term complication. As the frequency and severity of periods of acute rejection are the main risk factors for development of BOS, it follows that it is of utmost importance to prevent acute rejection. A substantial eVort has therefore been made to develop and introduce new immunosuppressant drugs, not only to prevent and treat acute and chronic rejection, but also with the hope of fewer side eVects. This review will focus on recently approved immunosuppressant drugs, some of their pharmacological properties, evidence of their eVectiveness in organ transplantation in general, and reported results in lung transplantation in particular. Furthermore, promising immunosuppressive drugs under investigation and the inhalation of cyclosporin or corticosteroids will be considered briefly.