Laboratory of Pneumology, Katholieke Universiteit Leuven and University Hospital Gasthuisberg, Leuven, Belgium.
J Heart Lung Transplant. 2010 Dec;29(12):1358-68. doi: 10.1016/j.healun.2010.05.023. Epub 2010 Jul 8.
Azithromycin may reverse or halt the decline of pulmonary function (FEV(1)) in bronchiolitis obliterans syndrome (BOS). In this study we investigated the effects of long-term azithromycin treatment in lung transplant recipients with BOS.
A retrospective, observational, cohort study was performed on 107 patients with BOS (Stages 0p/1/2/3, n = 23/62/20/2), who were treated with azithromycin for 3.1 ± 1.9 years. Patients were evaluated 6.3 ± 3.8 years after transplantation and assessed for evolution of FEV(1), bronchoalveolar lavage neutrophilia and overall survival after initiation of azithromycin. Survival curves were analyzed using the log-rank test. Cox proportional hazard survival regression analysis was performed to estimate hazard ratios of clinical variables predicting outcome.
FEV(1) increased ≥ 10% after 3 to 6 months of treatment in 40% of patients, of whom 33% later redeveloped BOS. FEV(1) further declined in 78% and stabilized in 22% of the remaining non-responders. Pre-treatment neutrophilia was higher in responders: 29.3% (9.3% to 69.7%) vs 11.5% (2.9% to 43.8%) (p = 0.025), in whom it significantly decreased to 4.2% (1.8% to 17.6%) (p = 0.041) after 3 to 6 months of azithromycin. Responders demonstrated better survival compared with non-responders (p = 0.050), with 6 and 21 patients, respectively, dying during follow-up (p = 0.027). Multivariate analysis identified initial azithromycin response and earlier post-transplant initiation of azithromycin to be protective for both BOS progression/relapse (hazard ratio [HR] = 0.12 [95% confidence interval 0.05 to 0.28], p < 0.0001; and HR = 0.98 [95% confidence interval 0.97 to 0.98], p < 0.0001, respectively) and retransplantation/death during follow-up (HR 0.10 [95% confidence interval 0.02 to 0.48], p = 0.004; and HR 0.96 [95% confidence interval 0.95 to 0.98], p < 0.0001, respectively).
Long-term azithromycin benefits pulmonary function and survival in BOS, particularly in patients with increased lavage neutrophilia.
阿奇霉素可能逆转或阻止闭塞性细支气管炎综合征（BOS）患者的肺功能（FEV1）下降。在这项研究中，我们调查了长期阿奇霉素治疗对 BOS 肺移植受者的影响。
对 107 例 BOS 患者（0p/1/2/3 期，n=23/62/20/2）进行了回顾性、观察性队列研究，这些患者接受了 3.1±1.9 年的阿奇霉素治疗。移植后 6.3±3.8 年对患者进行评估，评估 FEV1 的演变、支气管肺泡灌洗中性粒细胞增多和开始使用阿奇霉素后的总生存率。使用对数秩检验分析生存曲线。使用 Cox 比例风险生存回归分析估计预测结局的临床变量的危险比。
40%的患者在治疗 3 至 6 个月后 FEV1 增加≥10%，其中 33%的患者后来再次发生 BOS。78%的非应答者的 FEV1 进一步下降，22%的非应答者的 FEV1 稳定。治疗前中性粒细胞增多的患者应答率更高：29.3%（9.3%至 69.7%）与 11.5%（2.9%至 43.8%）（p=0.025），其中在接受阿奇霉素治疗 3 至 6 个月后，中性粒细胞显著减少至 4.2%（1.8%至 17.6%）（p=0.041）。与非应答者相比，应答者的生存率更好（p=0.050），分别有 6 名和 21 名患者在随访期间死亡（p=0.027）。多变量分析确定初始阿奇霉素反应和移植后早期开始使用阿奇霉素对 BOS 进展/复发（危险比[HR]分别为 0.12[95%置信区间 0.05 至 0.28]，p<0.0001；和 0.98[95%置信区间 0.97 至 0.98]，p<0.0001）和随访期间的再次移植/死亡（HR 0.10[95%置信区间 0.02 至 0.48]，p=0.004；和 HR 0.96[95%置信区间 0.95 至 0.98]，p<0.0001）具有保护作用。
长期阿奇霉素治疗可改善 BOS 的肺功能和生存率，特别是在灌洗中性粒细胞增多的患者中。
