title: Inhaled cyclosporine and pulmonary function in lung transplant recipients.
abstract: BACKGROUND
  Chronic rejection, manifesting as bronchiolitis obliterans, is the leading cause of death in lung transplant recipients. In our previously reported double-blinded, placebo-controlled trial comparing inhaled cyclosporine (ACsA) to aerosol placebo, the rate of bronchiolitis-free survival improved. However, an independent analysis of pulmonary function, a secondary endpoint of the trial, was not performed. We sought to determine the effect of ACsA, in addition to systemic immunosuppression, on pulmonary function.
  
  
  METHODS
  From 1998-2001, 58 patients were randomly assigned to inhale either 300 mg of ACsA (28 patients) or placebo aerosol (30 patients) 3 days a week for the first 2 years after transplantation. Longitudinal changes in pulmonary function of ACsA patients were compared to aerosol placebo patients. In another analysis, the rate of decline from 6-month maximum FEV(1) in randomized patients was compared to the rate of decline in patients receiving conventional immunosuppression from the Novartis transplant database (644 patients, 12 centers worldwide, transplanted from 1990-1995).
  
  
  RESULTS
  The average duration of ACsA and aerosol placebo was 400 days +/- 306 and 433 +/- 256, respectively. The change in FEV(1) of ACsA patients (adjusted for Cytomegalovirus (CMV) mismatch and transplant type, followed for a maximum duration of 4.6 years) was superior to the aerosol placebo controls (9.0 +/- 71.4 mL/year vs. -107.9 +/- 55.3, p = 0.007). The FEF(25-75) decreased by -220.3 +/- 117.7 L/(second x year) vs. -412.2 +/- 139.2, p = 0.07, respectively. Similarly, percent FEV(1) decline from maximal values was improved in ACsA patients compared to aerosol placebo and Novartis controls (ACsA -0.43 +/- 1.12%/year vs. aerosol placebo -4.08 +/- 1.4, p = 0.04; ACsA vs. Novartis -4.7 +/- 0.31, p = 0.007). Single-lung recipients receiving ACsA showed improvement in FEV(1) compared to Novartis controls (FEV(1) -0.8 +/- 1.8%/year vs. -4.94 +/- 0.4, p = 0.03) but double-lung recipients showed improvement compared to aerosol placebo controls only (FEV(1) -0.28 +/- 1.22%/year vs. -8.53 +/- 5.95, p = 0.048).
  
  
  CONCLUSIONS
  In this single center trial, ACsA appears to ameliorate important pulmonary function parameters in lung transplant recipients compared to aerosol placebo and historical control patients. Single- and double-lung transplant recipients may not respond uniformly to treatment, and ongoing randomized trials in lung transplant recipients using ACsA may help elucidate our findings.
authors: Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA.
authors: Soleyah
authors: S
authors: Groves
authors: Marek
authors: M
authors: Galazka
authors: Bruce
authors: B
authors: Johnson
authors: Timothy
authors: T
authors: Corcoran
authors: Avelino
authors: A
authors: Verceles
authors: Edward
authors: E
authors: Britt
authors: Nevins
authors: N
authors: Todd
authors: Bartley
authors: B
authors: Griffith
authors: Gerald C
authors: GC
authors: Smaldone
authors: Aldo
authors: A
authors: Iacono
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine