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Background Conventional regimens of immunosuppressive drugs often do not prevent chronic rejection after lung transplantation. Topical delivery of cyclosporine in addition to conventional systemic immunosuppression might help prevent acute and chronic rejection events.
Methods We conducted a single-center, randomized, double-blind, placebo-controlled trial of inhaled cyclosporine initiated within six weeks after transplantation and given in addition to systemic immunosuppression. A total of 58 patients were randomly assigned to inhale either 300 mg of aerosol cyclosporine (28 patients) or aerosol placebo (30 patients) three days a week for the first two years after transplantation. The primary end point was the rate of histologic acute rejection.
Results The rates of acute rejection of grade 2 or higher were similar in the cyclosporine and placebo groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46 episode (95 percent confidence interval, 0.33 to 0.64) per patient per year, respectively (P=0.87 by Poisson regression). Survival was improved with aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and 14 deaths among patients receiving placebo (relative risk of death, 0.20; 95 percent confidence interval, 0.06 to 0.70; P=0.01). Chronic rejection–free survival also improved with cyclosporine, as determined by spirometric analysis (10 events in the cyclosporine group and 20 events in the placebo group; relative risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82; P=0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk, 0.27; 95 percent confidence interval, 0.11 to 0.67; P=0.005). The risks of nephrotoxic effects and opportunistic infection were similar for patients in the cyclosporine group and the placebo group.
Conclusions Inhaled cyclosporine did not improve the rate of acute rejection, but it did improve survival and extend periods of chronic rejection–free survival. (ClinicalTrials.gov number, NCT00268515
[ClinicalTrials.gov]
.)
Source Information
From the Division of Pulmonary, Allergy and Critical Care Medicine (A.T.I., B.A.J., W.F.G., J.G.Y., T.E.C., D.A.S., J.H.D.), the Department of Pathology (A.Z., S.A.Y.), and the Thomas E. Starzl Transplantation Institute (J.J.F.), University of Pittsburgh Medical Center; and the Division of Cardiothoracic Surgery, University of Pittsburgh (K.R.M.) — all in Pittsburgh; the Division of Pulmonary and Critical Care Medicine, State University of New York at Stony Brook, Stony Brook (G.C.S.); the Department of Pharmacy, University of Southern California, Los Angeles (G.J.B.); and the Division of Cardiothoracic Surgery, University of Maryland, Baltimore (B.P.G.).
Address reprint requests to Dr. Iacono at the Division of Pulmonary Transplantation and Pulmonary and Critical Care Medicine, Medical School Teaching Facility 800, University of Maryland School of Medicine, 10 S. Pine St., Baltimore, MD 21201, or at aiacono{at}medicine.umaryland.edu.
Related Letters:
Inhaled Cyclosporine in Lung Transplantation
Verleden G. M., Dupont L. J., Iacono A. T., Johnson B. A., Corcoran T. E.
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N Engl J Med 2006;
354:1752-1753, Apr 20, 2006.
Correspondence
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