Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome.
BACKGROUND
Bronchiolitis obliterans syndrome (BOS) is a leading cause of morbidity and mortality after lung and heart-lung transplantation. Present treatment is directed at the augmentation of pharmacologic immunosuppression.


METHODS
This study examines the effect of substituting cyclosporine with tacrolimus on the forced expiratory volume in 1 second (FEV(1)) and on the forced expiratory flow between 25% and 75% of vital capacity (FEF(25%-75%)) in 32 patients who developed BOS. The proportional rates of decline of FEV(1) and FEF(25%-75%) before and after treatment with tacrolimus were calculated. The actuarial survival of responders and non-responders to tacrolimus was compared. Pre-operative and post-operative factors were investigated to determine any difference between the 2 groups.


RESULTS
There were significant reductions in the rates of decline of FEV(1) and FEF(25%-75%) when the rates in the 3 months before conversion to tacrolimus were compared with subsequent rates at 0 to 3 months, 3 to 6 months, 6 to 9 months and 9 to 12 months after conversion. The rates of decline of FEV(1) and FEF(25%-75%) in the 3 months before conversion were 0.11 liters/month and 0.13 liters/s per month, respectively. This compares with the rates of decline for FEV(1) and FEF(25%-75%) for the 3 months after conversion to tacrolimus of 0.04 liters/month (p = 0.023) and 0.04 liters/s per month (p = 0.022), respectively. The actuarial survival at 1 year from the time of conversion to tacrolimus for the responder sub-group and the non-responder sub-group were 89.2% and 75%, respectively, and at 4 years after conversion were 61.3% and 56.3%, respectively (p = 0.92).


CONCLUSIONS
Tacrolimus rescue therapy is effective at stabilizing lung function in patients with BOS, and this effect is apparent up to 12 months after conversion from cyclosporine.
Cairn
J
J
Department of Transplant Medicine, National Heart and Lung Institute, Harefield, Middlesex, UK.
Yek
T
T
Banner
N R
NR
Khaghani
A
A
Hodson
M E
ME
Yacoub
M
M
D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D016041:Heart-Lung Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008168:Lung / Q000503:physiopathology*; D016040:Lung Transplantation; D013147:Spirometry; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus