Pulmonary Diseases, University Medical Centre Groningen Thoraxcentre, Groningen, The Netherlands.
Transplantation Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
BMJ Open Respir Res. 2019 Oct 15;6(1):e000465. doi: 10.1136/bmjresp-2019-000465. eCollection 2019.
Azithromycin stabilises and improves lung function forced expiratory volume in one second (FEV) in lung transplantation patients with bronchiolitis obliterans syndrome (BOS). A post hoc analysis was performed to assess the long-term effect of azithromycin on FEV, BOS progression and survival .
Eligible patients recruited for the initial randomised placebo-controlled trial received open-label azithromycin after 3 months and were followed up until 6 years after inclusion (n=45) to assess FEV, BOS free progression and overall survival.
FEV in the placebo group improved after open-label azithromycin and was comparable with the treatment group by 6 months. FEV decreased after 1 and 5 years and was not different between groups. Patients (n=18) with rapid progression of BOS underwent total lymphoid irradiation (TLI). Progression-free survival (log-rank test p=0.40) and overall survival (log-rank test p=0.28) were comparable. Survival of patients with early BOS was similar to late-onset BOS (log-rank test p=0.74).
Long-term treatment with azithromycin slows down the progression of BOS, although the effect of TLI may affect the observed attenuation of FEV decline. BOS progression and long-term survival were not affected by randomisation to the placebo group, given the early cross-over to azithromycin and possibly due to TLI in case of further progression. Performing randomised placebo-controlled trials in lung transplantation patients with BOS with a blinded trial duration is feasible, effective and safe.
阿奇霉素可稳定和改善患有闭塞性细支气管炎综合征（BOS）的肺移植患者的一秒用力呼气量（FEV）。进行了一项事后分析，以评估阿奇霉素对 FEV、BOS 进展和生存率的长期影响。
符合条件的患者入选初始随机安慰剂对照试验，在 3 个月后接受开放标签阿奇霉素治疗，并随访至纳入后 6 年（n=45），以评估 FEV、BOS 无进展和总体生存率。
安慰剂组的 FEV 在接受开放标签阿奇霉素治疗后得到改善，并在 6 个月时与治疗组相当。FEV 在 1 年和 5 年后下降，两组之间无差异。BOS 快速进展的患者（n=18）接受了全淋巴照射（TLI）。无进展生存率（对数秩检验 p=0.40）和总体生存率（对数秩检验 p=0.28）无差异。早期 BOS 患者的生存率与晚期 BOS 患者相似（对数秩检验 p=0.74）。
长期使用阿奇霉素可减缓 BOS 的进展，尽管 TLI 的效果可能会影响观察到的 FEV 下降的减弱。鉴于早期交叉至阿奇霉素，以及在进一步进展时可能进行 TLI，随机分配至安慰剂组对 BOS 进展和长期生存率没有影响。在患有 BOS 的肺移植患者中进行盲法试验持续时间的随机安慰剂对照试验是可行、有效和安全的。
