Department of Pulmonology, University Hospital Zurich, Switzerland.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Swiss Med Wkly. 2022 Jul 31;152:w30206. doi: 10.4414/smw.2022.w30206. eCollection 2022 Jul 18.
Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction.
In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline.
37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = -0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90-1.06, p = 0.64 over a period of 382.97 patient-years).
Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors.
慢性肺移植物功能障碍的发展是肺移植后生存的一个限制因素。我们评估了免疫抑制剂霉酚酸酯的剂量或其活性代谢物霉酚酸的血浆浓度是否会影响慢性肺移植物功能障碍的发展。
在这项回顾性队列研究中，我们招募了 71 名在 2010 年至 2014 年期间接受肺移植的患者，这些患者在移植后第一年存活下来，直至 2021 年 7 月 1 日。使用具有时变协变量的事件时间分析 Cox 比例风险回归模型（18431 次 MPA、霉酚酸酯剂量、淋巴细胞测量值）来预测慢性肺移植物功能障碍，调整了社会人口因素和基线时的肺功能。
37 名患者未发生慢性肺移植物功能障碍（年龄 41.3 ± 15.6 岁，基线 FEV1 预测值的 95.5 ± 19.1%），34 名患者发生慢性肺移植物功能障碍（年龄 50.9 ± 13.3 岁，基线 FEV1 预测值的 102.2 ± 25.4%）。两组之间的平均霉酚酸浓度无显著差异（2.8 ± 1.7 和 3.0 ± 2.3 mg/l；p = 0.724）。在移植后的前 4 年，死亡率为 25%。到移植后的第 9 年，共有 50%的患者死亡。霉酚酸酯剂量、霉酚酸（r2 = 0.02，p <0.001）以及淋巴细胞水平（r2 = -0.007，p <0.001）之间存在剂量效应关系，但只有传统的风险因素年龄可预测慢性肺移植物功能障碍。连续测量的霉酚酸并未预测慢性肺移植物功能障碍（危险比 0.98，95%置信区间 0.90-1.06，p = 0.64，随访 382.97 患者年）。
霉酚酸酯剂量和霉酚酸与慢性肺移植物功能障碍的发展无关。因此，霉酚酸酯剂量或霉酚酸的血浆浓度不是与器官排斥相关的主要因素，但慢性肺移植物功能障碍可能受到免疫抑制的其他成分或其他因素的影响。
