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Current Opinion in Organ Transplantation:
Volume 8(4) December 2003 pp 327-333
Inhalation cyclosporine: a new use in lung transplantation?
Iacono, Aldo T. ; McCurry, Kenneth R. ; Corcoran, Timothy E.
Divisions of Pulmonary, Allergy, and Critical Care Medicine and
Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Correspondence to:
Aldo T. Iacono, MD,
Pulmonary Transplantation and Pulmonary, Allergy, and Critical Care Medicine,
University of Pittsburgh Medical Center, NW 628,
Montefiore University Hospital,
3459 Fifth Avenue,
Pittsburgh, PA 15213, USA
Tel: 412 647 5473; fax:412 647 7875;
e-mail: iaconoat@msx.upmc.edu
Studies were funded in part by National Institutes of Health grant HL05949001
and by American Lung Association grant CG-013-N.
Abstract
Purpose of review: Outcomes after lung transplantation are poor, largely because of chronic rejection. Increasing immunosuppression to control rejection frequently results in toxicity and opportunistic infection. Aerosol cyclosporine was developed with the rationale that high concentrations of cyclosporine delivered to the lung by aerosol inhalation would result in improved rejection control with limited systemic cyclosporine exposure. Here we describe the developmental history of inhaled cyclosporine and review our ongoing trials to evaluate its use as a promising new therapy for lung transplant recipients. Recent findings: After demonstrating safety and efficacy in animal transplant models, clinical trials using rescue open-label, inhaled cyclosporine in human lung transplant recipients with bronchiolitis obliterans and refractory acute rejection demonstrated improvement in pulmonary function and survival. A therapeutic response was dependent on the absolute quantity of cyclosporine measured within the allograft. In 1998, a randomized, placebo-controlled trial was initiated using inhaled cyclosporine in addition to oral immunosuppression. An interim analysis showed that lung function was superior in patients randomized to inhaled cyclosporine who deposited at least 5 mg in the allograft compared with placebo aerosol.
Summary:
Inhaled cyclosporine was safe and improved outcomes in lung transplant recipients with refractory acute and chronic rejection. An interim analysis of a placebo-controlled, randomized trial showed that inhaled cyclosporine improves lung function compared with placebo aerosol. Inhaled cyclosporine should become a standard treatment after lung
transplantation if a final analysis of this recently completed trial demonstrates a reduction in the incidence of chronic rejection.
© 2003 Lippincott Williams & Wilkins, Inc.
Reproduction of copyrighted material is at the discretion of the individual, and is made pursuant to the individual's election under 17 USC 107, the Fair Use exception to Federal copyright restrictions.
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