Yates Bryan, Murphy Desmond M, Forrest Ian A, Ward Chris, Rutherford Robert M, Fisher Andrew J, Lordan James L, Dark John H, Corris Paul A
The William Leech Centre for Lung Research, The Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK.
Am J Respir Crit Care Med. 2005 Sep 15;172(6):772-5. doi: 10.1164/rccm.200411-1537OC. Epub 2005 Jun 23.
A recent pilot study noted clinical benefit of macrolide therapy in the management of six lung transplant recipients with bronchiolitis obliterans syndrome (BOS), a condition previously regarded as irreversible.
To examine the effect of low-dose macrolides on lung function in lung allograft recipients with established BOS and to assess whether this benefit is sustained.
We retrospectively evaluated the effect of azithromycin (250 mg alternate days) on clinical status and lung function in 20 allograft recipients with established BOS, confirmed by decline in FEV(1) or FEF(25-75); consistent high-resolution computed tomography findings; and exclusion of acute rejection, infection, or anastomatic complications. Azithromycin was introduced at mean 82 months after transplantation. BOS staging at initiation of treatment was BOS 3 (10), BOS 2 (2), BOS 1 (6), and BOS0-p (2). All patients were on maintenance immunosuppression comprising cell-cycle inhibitor, oral corticosteroids, and calcineurin inhibitor.
There was a significant increase in FEV(1) of median 110 ml (range, -70 to 730 ml) between baseline and 3 months of azithromycin therapy (p = 0.002). This improvement was sustained beyond 3 months in the majority of patients, who had initially benefited from azithromycin (up to 11 months follow up).
This case series confirms the benefit of azithromycin in not only halting, but reversing the declining lung function seen in patients with BOS. This benefit appears to be maintained over time. Low-dose macrolides offer a new and exciting therapeutic strategy for the treatment of progressive BOS, and further clinical and translational mechanistic studies are required.
最近一项初步研究指出，大环内酯类药物治疗对6例患有闭塞性细支气管炎综合征（BOS）的肺移植受者具有临床益处，该病症以前被认为是不可逆的。
研究低剂量大环内酯类药物对已确诊BOS的肺移植受者肺功能的影响，并评估这种益处是否能持续。
我们回顾性评估了阿奇霉素（隔日250毫克）对20例已确诊BOS的移植受者临床状况和肺功能的影响，这些患者通过第一秒用力呼气容积（FEV(1)）或用力呼气中期流速（FEF(25-75)）下降得以确诊；高分辨率计算机断层扫描结果一致；且排除了急性排斥反应、感染或吻合口并发症。阿奇霉素在移植后平均82个月开始使用。治疗开始时的BOS分期为BOS 3期（10例）、BOS 2期（2例）、BOS 1期（6例）和BOS0-p期（2例）。所有患者均接受维持性免疫抑制治疗，包括细胞周期抑制剂、口服糖皮质激素和钙调神经磷酸酶抑制剂。
在阿奇霉素治疗的基线期和3个月之间，第一秒用力呼气容积（FEV(1)）中位数显著增加110毫升（范围为-70至730毫升）（p = 0.002）。在大多数最初受益于阿奇霉素的患者中（随访长达11个月），这种改善在3个月后仍持续存在。
该病例系列证实了阿奇霉素不仅对阻止BOS患者肺功能下降有益，而且能使其逆转。这种益处似乎会随着时间持续存在。低剂量大环内酯类药物为进行性BOS的治疗提供了一种新的、令人兴奋的治疗策略，还需要进一步的临床和转化机制研究。
