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Preservation of post-transplant lung function with aerosol cyclosporin

¹ Division of Pulmonary, Allergy and Critical Care Medicine, ³ Division of Cardiothoracic Surgery, and ⁴ Division of Transplant Pathology, University of Pittsburgh, Pittsburgh, PA, ² Pulmonary/Critical Care Medicine, SUNY at Stony Brook, Stony Brook, NY, and ⁵ Division of Cardiac Surgery and Cardiopulmonary Transplantation, University of Maryland Medical Center, Baltimore, USA

CORRESPONDENCE: T.E. Corcoran, UPMC MUH NW628, 3459 Fifth Ave., Pittsburgh, 15213, USA. Fax: 1 4126477875. E-mail: corcorante@msx.upmc.edu

Keywords: aerosol cyclosporin, aerosol deposition, lung transplantation

Received: May 28, 2003
Accepted September 24, 2003

This research was supported by grants from the National Heart, Lung and Blood Institute, and the American Lung Association. The cyclosporin powder was provided by Novartis Pharmaceuticals.

Post-lung transplant use of aerosol cyclosporin (ACsA) is considered by examining the relationship between deposited aerosol dose and effect.

In a sub-study of placebo controlled trials of ACsA as a rejection prophylaxis, 15 drug subjects received aerosol dose quantification tests to gage their ability to effectively deposit the nebulised drug in their transplanted lung(s). A total of seven placebo subjects received mock deposition tests. The deposited doses and mock doses were compared to changes in the forced expiratory volume in one second, at six time points during the 2-yr trial period (ACsA was started within 6 weeks post-transplant).

Linear relationships were demonstrated between deposited dose and improvement in lung function in the drug subjects at all intervals. Mock dose data from placebo subjects did not demonstrate similar correlation. Based on these results, subjects were grouped by dose and compared. Subjects depositing 5 mg of the drug in the periphery of their transplant(s) had improving pulmonary function on average. Low-dose and placebo subjects demonstrated declines, more A2–A4 rejection events in the latter portion of the trial, and more chronic rejection beyond the end of the trial.

A dose-to-effect relationship is demonstrated for aerosol cyclosporin in terms of pulmonary function and biopsy proven rejection.

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				A. T. Iacono, B. A. Johnson, W. F. Grgurich, J. G. Youssef, T. E. Corcoran, D. A. Seiler, J. H. Dauber, G. C. Smaldone, A. Zeevi, S. A. Yousem, et al. A Randomized Trial of Inhaled Cyclosporine in Lung-Transplant Recipients N. Engl. J. Med., January 12, 2006; 354(2): 141 - 150. [Abstract] [Full Text] [PDF]