Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome

J Heart Lung Transplant. 2003 Jan;22(1):50-7. doi: 10.1016/s1053-2498(02)00548-x.


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.

MeSH terms

  • Bronchiolitis Obliterans / drug therapy*
  • Bronchiolitis Obliterans / immunology
  • Bronchiolitis Obliterans / physiopathology
  • Cyclosporine / therapeutic use*
  • Forced Expiratory Volume
  • Heart-Lung Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lung / physiopathology*
  • Lung Transplantation*
  • Spirometry
  • Tacrolimus / therapeutic use*
  • Time Factors


  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus