Success with lung transplantation has largely been due to the introduction of cyclosporine which has proved effective in controlling lung allograft refection. Nevertheless, acute and chronic rejection are prevalent in spite of immunosuppressive drug regimens based on oral cyclosporine. In fact, rejection is more common in recipients of lung allografts than those who receive other solid organs. Acute rejection is treated with pulsed methylprednisolone and anti-lymphocyte globulin and consequently recipients are subject to increased risk of infection and drug toxicity. We hypothesize that delivery of cyclosporine to the transplanted lung by aerosol inhalation achieves higher concentrations of cyclosporine in the graft than when it is delivered via the bloodstream and that higher concentrations in the graft will prevent rejection more effectively that systemic immune suppression with the same or reduced toxicity. Clinical trials at the University of Pittsburgh have shown safety and efficacy of aerosolized cyclosporine utilized as rescue in over 40 patients with refractory rejection unresponsive to conventional augmented immune therapy. In this protocol, we propose a double blinded placebo controlled trial evaluating the efficacy of aerosolized cyclosporine given in addition to the standard oral immunosuppressive drug regimen, in preventing acute rejection immediately after lung transplantation. Deposition of aerosol cyclosporine will be measured by radioisotopic techniques to optimize the dose to the allograft and define the relationship between dose deposited and improvement in parameters of rejection. The results of this study will help determine whether regional delivery of aerosol cyclosporine is effective as prevention and treatment of acute rejection in lung transplant recipients and better define the potential toxicities and beneficial effects of delivery of immunosuppressive medication to the lower respiratory tract.
| Iacono, Aldo T; Johnson, Bruce A; Grgurich, Wayne F et al. (2006) A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med 354:141-50 |
| Burkart, Gilbert J; Smaldone, Gerald C; Eldon, Michael A et al. (2003) Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Pharm Res 20:252-6 |
