Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases, Metabolism & Ageing, Division of Respiratory Diseases, KU Leuven, Leuven, Belgium.
Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.
J Heart Lung Transplant. 2019 May;38(5):516-527. doi: 10.1016/j.healun.2018.11.014. Epub 2018 Dec 6.
Chronic lung allograft dysfunction (CLAD) is a major cause of post‒lung transplant mortality, with limited medical treatment options. In this study we assessed the association of montelukast treatment with pulmonary function and outcome in lung transplant recipients with progressive CLAD.
We performed a retrospective study of all lung transplant recipients transplanted between July 1991 and December 2016 at our center and who were treated for at least 3 months with montelukast for progressive CLAD, despite at least 3 months of prior azithromycin therapy. Main outcome parameters included evolution of pulmonary function and progression-free and overall survival.
A total of 153 patients with CLAD (115 with bronchiolitis obliterans syndrome and 38 with restrictive allograft syndrome) were included, of whom 46% had a forced expiratory volume in 1 second (FEV) measure of between 66% and 80%, 31% an FEV between 51% and 65%, and 23% an FEV ≤50% of best post-operative FEV at start of montelukast. Montelukast was associated with attenuation in rate of FEV decline after 3 and 6 months, respectively (both p < 0.0001). Patients in whom FEV improved or stabilized after 3 months of montelukast (81%) had significantly better progression-free (p < 0.0001) and overall (p = 0.0002) survival after CLAD onset, as compared to those with further decline of FEV (hazard ratio [HR] 2.816, 95% confidence interval [CI] 1.450 to 5.467, p = 0.0022 for overall survival after CLAD onset in risk-adjusted multivariate analysis).
Montelukast was associated with a significant attenuation in rate of FEV decline in a substantial proportion of patients with established CLAD, which correlated with better outcome. Further study is required regarding use of montelkast.
慢性肺移植物功能障碍（CLAD）是肺移植后死亡的主要原因，治疗选择有限。本研究评估了孟鲁司特治疗对进展性 CLAD 肺移植受者肺功能和结局的影响。
我们对 1991 年 7 月至 2016 年 12 月期间在本中心接受肺移植且至少接受 3 个月孟鲁司特治疗进展性 CLAD 的患者进行了回顾性研究，尽管他们已经接受了至少 3 个月的阿奇霉素治疗。主要观察指标包括肺功能的变化、无进展生存期和总生存期。
共纳入 153 例 CLAD 患者（115 例为细支气管炎闭塞性综合征，38 例为限制型移植物综合征），其中 46%的患者第 1 秒用力呼气量（FEV）为最佳术后 FEV 的 66%80%，31%的患者 FEV 在 51%65%之间，23%的患者 FEV 为最佳术后 FEV 的≤50%。孟鲁司特治疗后 3 个月和 6 个月时，FEV 下降率分别明显减慢（均 p<0.0001）。孟鲁司特治疗 3 个月后 FEV 改善或稳定的患者（81%）在 CLAD 发病后的无进展生存期（p<0.0001）和总生存期（p=0.0002）显著优于 FEV 进一步下降的患者（风险比 2.816，95%置信区间 1.450~5.467，p=0.0022，在调整后的多变量分析中 CLAD 发病后的总生存期）。
在相当一部分确诊 CLAD 的患者中，孟鲁司特治疗可显著减缓 FEV 下降率，与更好的结局相关。尚需进一步研究孟鲁司特的应用。
