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

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Abstract

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 (FEV1) and on the forced expiratory flow between 25% and 75% of vital capacity (FEF25%-75%) in 32 patients who developed BOS. The proportional rates of decline of FEV1 and FEF25%-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 FEV1 and FEF25%-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 FEV1 and FEF25%-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 FEV1 and FEF25%-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.

Section snippets

Materials and methods

Two hundred forty-eight patients underwent 253 heart–lung or lung transplants between January 1, 1990 and December 31, 1995 (heart–lung transplant [HLTx] = 75; double-lung transplant [DLTx] = 30; bilateral single-lung transplant [BiSLTx] = 19; single-lung transplant [SLTx] = 129). Ninety-four patients developed BOS. BOS was diagnosed using International Society for Heart and Lung Transplantation (ISHLT) criteria.4 Lung function data before and after conversion to tacrolimus were available for

Results

Thirty-two patients who were converted from cyclosporine to tacrolimus for BOS were included in this study. At the time of diagnosis of BOS, 21 patients were classified as BOS Grade 1a, 3 as BOS Grade 1b, 5 as BOS Grade 2a, 1 as BOS Grade 2b and 2 as BOS Grade 3a.

There were 19 patients in the responder sub-group and 8 in the non-responder group, and 5 patients had insufficient lung function data (due mostly to a lack of spirometric data in the 3 months before conversion to tacrolimus) for

Discussion

This study has defined the range of clinical responses of lung transplant patients to conversion from cyclosporine- to tacrolimus-based immunosuppression after diagnosis of BOS. The majority of patients (n = 19) showed a reduction in the rate of deterioration of lung function. Non-response to conversion to tacrolimus was associated with a poor prognosis as borne out by a trend in the actuarial survival data, although the comparison between responder and non-responder sub-groups did not achieve

Acknowledgements

The authors gratefully acknowledge Jackie Turner, medical statistician, for the contribution to the statistical analyses.

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