Tacrolimus as rescue therapy for bronchiolitis obliterans syndrome.
BACKGROUND
Chronic lung allograft rejection manifested by sustained declines in lung function is the most common cause of late death after lung transplantation. Numerous strategies have shown variable results. We sought to evaluate the effect of FK506 (tacrolimus) on bronchiolitis obliterans syndrome (BOS) after lung transplantation.


METHODS
A single-center open study was conducted of 15 patients whose treatment was converted to tacrolimus from cyclosporine. Of the 15, 12 patients had BOS characterized by sustained loses in lung function while receiving cyclosporine. Rate of decline of forced expiratory volume in 1 second (FEV1) for the 12 patients was calculated before and after administration of tacrolimus. Biochemical changes before and after conversion were compared for the entire group.


RESULTS
Median monthly rate of decline in FEV1 was significantly reduced after administration of tacrolimus (5.3% vs 1.1%; p = 0.002). Forced vital capacity did not change significantly. No subjects experienced at least a 10% improvement in FEV1. At least a 10% further decline in FEV1 was noted in five subjects, and seven subjects had no change (i.e., within 10% of baseline). A minor nonsignificant increase in creatinine occurred after administration of tacrolimus. Blood cell count, electrolytes, and liver enzymes remained unchanged. The median change in fasting blood glucose was +0.7 mmol/L (p = 0.02).


CONCLUSIONS
Although tacrolimus does not reverse changes in FEV1 with BOS, in this nonrandomized study it seemed to be associated with a decrease in the rate of decline in lung function and no significant sustained toxicity. Further studies are necessary to substantiate this observation.
Kesten
S
S
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Chaparro
C
C
Scavuzzo
M
M
Gutierrez
C
C
D000328:Adult; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006084:Graft Rejection / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000503:physiopathology; D013147:Spirometry; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016559:Tacrolimus