Verleden Geert M, Dupont Lieven J, Van Raemdonck Dirk, Vanhaecke Johan
Department of Respiratory Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
J Heart Lung Transplant. 2003 Aug;22(8):908-13. doi: 10.1016/s1053-2498(02)00815-x.
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.
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.
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.
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.
既往研究表明，在肺移植后慢性排斥反应期间，将免疫抑制治疗从环孢素（CyA）转换为他克莫司（FK）可能会阻止一秒用力呼气量（FEV₁）下降。呼气一氧化氮（eNO）在慢性排斥反应期间已被证明会升高。我们报告了肺移植后慢性排斥反应患者从CyA转换为FK治疗后，FEV₁随之稳定且eNO降低。
我们采用前瞻性设计。该研究纳入了10例肺移植患者（5例男性和5例女性），移植时平均年龄为44±14岁，FEV₁呈进行性下降，归因于慢性排斥反应。4例患者接受了心肺移植，3例接受了序贯单肺移植，3例接受了单肺移植。从CyA转换为FK发生在移植后36±23个月（时间0）。根据标准化的欧洲呼吸学会（ERS）标准，使用化学发光分析仪测量eNO。
在时间0时，有6例患者处于闭塞性细支气管炎综合征（BOS）0 - p期，FEV₁平均下降15±3%；2例处于BOS 1期；2例处于BOS 2期。与术后最佳FEV₁相比，直到时间0时FEV₁呈进行性且显著下降，从2.56±0.9升降至2.03±0.94升（p = 0.0047）。此后，FEV₁稳定：时间0时为2.03±0.94升，6个月后为2.05±0.94升（p =无显著性差异）。同时，在时间0前的6个月内，eNO逐渐升高，从最佳FEV₁时的11.4±2.5 ppb升至时间0时的20.5±14.8 ppb。转换后eNO呈非显著性下降，从20.5±14.8 ppb降至14.9±5.4 ppb。在研究的两个时间点，BOS 0 - p期患者与更高BOS分期患者的eNO水平均无显著差异。
本研究表明，从CyA转换为FK可使肺移植慢性排斥反应患者的肺功能稳定。FEV₁的这种稳定伴随着eNO的降低，表明这种治疗转换可减轻慢性排斥反应过程中气道的炎症。因此，测量eNO在指导肺移植后慢性排斥反应的治疗中可能极具价值。
