Effect of switching from cyclosporine to tacrolimus on exhaled nitric oxide and pulmonary function in patients with chronic rejection after lung transplantation

Abstract

Background: Previous studies have demonstrated that shifting immunosuppressive therapy from cyclosporine (CyA) to tacrolimus (FK) may arrest the decline in forced expiratory volume in 1 second (FEV(1)) during chronic rejection after lung transplantation. Exhaled nitric oxide (eNO) has been shown to be elevated during chronic rejection. We report the concomitant stabilization of FEV(1) and decrease in eNO after changing from CyA to FK therapy in patients with chronic rejection after lung transplantation.

Methods: We used a prospective design. The study included 10 lung transplant patients (5 men and 5 women), mean age 44 +/- 14 years at time of transplantation, with a progressive decline in FEV(1) that was attributed to chronic rejection. Four patients underwent heart-lung transplantation and 3 had a sequential single and 3 a single-lung transplantation. The switch from CyA to FK occurred at 36 +/- 23 months after transplantation (Time 0). The eNO was measured using a chemiluminescence analyzer, according to standardized European Respiratory Society (ERS) criteria.

Results: At Time 0, there were 6 patients in bronchiolitis obliterans syndrome (BOS) Stage 0-p, with a mean decline in FEV(1) of 15 +/- 3%; 2 in BOS Stage 1; and 2 in BOS Stage 2. Compared with the best post-operative FEV(1), there was a progressive and significant decline until Time 0, from 2.56 +/- 0.9 liters to 2.03 +/- 0.94 liters (p = 0.0047). Thereafter, FEV(1) stabilized: 2.03 +/- 0.94 liters at Time 0 and 2.05 +/- 0.94 liters 6 months later (p = non-significant). Concomitantly, there was a gradual increase in eNO during the 6 months before Time 0, from 11.4 +/- 2.5 ppb at the time of best FEV(1) to 20.5 +/- 14.8 ppb at Time 0. After switching, there was a non-significant decline in eNO, from 20.5 +/- 14.8 ppb to 14.9 +/- 5.4 ppb. There was no significant difference in eNO levels between the patients in BOS Stage 0-p and patients in higher BOS stages at either timepoint in the study.

Conclusions: This study illustrates that a switch from CyA to FK can stabilize pulmonary function in lung transplant patients with chronic rejection. This stabilization of FEV(1) is accompanied by a decrease in eNO, indicating that this treatment shift can reduce inflammation of airways during the course of chronic rejection. Consequently, measuring eNO may be extremely valuable in guiding the treatment of chronic rejection after lung transplantation.