title: Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.
abstract: BACKGROUND
  Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS.
  
  
  METHODS
  Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy.
  
  
  RESULTS
  Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied.
  
  
  CONCLUSIONS
  For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.
authors.affiliation: Division of Pulmonary Medicine, University of Utah, Salt Lake City, Utah 84132-1001, USA. barabara.cahill@hsc.utah.edu
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Cahill
authors.forename: K Troy
authors.initials: KT
authors.lastname: Somerville
authors.forename: Jason A
authors.initials: JA
authors.lastname: Crompton
authors.forename: Susan T
authors.initials: ST
authors.lastname: Parker
authors.forename: Mary K
authors.initials: MK
authors.lastname: O'Rourke
authors.forename: James C
authors.initials: JC
authors.lastname: Stringham
authors.forename: S V
authors.initials: SV
authors.lastname: Karwande
mesh_terms: D001989:Bronchiolitis Obliterans / Q000188:drug therapy*; D065095:Calcineurin Inhibitors; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013147:Spirometry; D014184:Transplantation, Homologous
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011241:Prednisone; D020123:Sirolimus