Dusmet M, Maurer J, Winton T, Kesten S
Toronto Lung Transplant Program, Toronto Hospital, Ontario, Canada.
J Heart Lung Transplant. 1996 Sep;15(9):948-54.
Methotrexate has been used successfully to treat refractory or recurrent rejection in heart transplant recipients. We therefore conducted an open pilot study to determine whether methotrexate is useful in the treatment of chronic rejection after lung transplantation.
Between December 1993 and January 1995 methotrexate was prescribed to 10 patients with persistent or progressive bronchiolitis obliterans despite multiple attempts to control the chronic rejection with conventional treatment (pulse steroids or antilymphocyte products, or both). Data from the nine patients with a minimum of 6 months of follow-up were collected.
No patients have died. The spirometry data of the eight patients with declining values of forced expiratory volume in 1 second are presented. Before initiation of methotrexate therapy the median decline in forced expiratory volume in 1 second was 1.4 +/- 0.8 L, or 43% +/- 17%, from the highest preinterventional forced expiratory volume in 1 second value during the preceding 12 months. At 6 months the median decline in forced expiratory volume in 1 second from the time methotrexate therapy was started was 0.1 +/- 0.2 L, or 3% +/- 11%. At 9 months (n = 6) the value was 0.2 +/- 0.2 L, or 6% +/- 12%. At 12 months (n = 5) the median decline was 0.4 +/- 0.3 L, or 9% +/- 16%. In two patients there has been no further decline in forced expiratory volume in 1 second since methotrexate therapy was started (one patient has had a slight but sustained improvement). Five patients have had a reduction in forced expiratory volume in 1 second of 10% or less at most recent follow-up, and only one patient has derived no apparent benefit from methotrexate therapy. Toxicity has been minimal.
Methotrexate is a potentially promising therapeutic alternative in the therapy of bronchiolitis obliterans syndrome in lung transplant recipients.
甲氨蝶呤已成功用于治疗心脏移植受者的难治性或复发性排斥反应。因此，我们开展了一项开放性初步研究，以确定甲氨蝶呤是否对治疗肺移植后的慢性排斥反应有效。
在1993年12月至1995年1月期间，尽管多次尝试用传统治疗方法（冲击性使用类固醇或抗淋巴细胞制品，或两者并用）控制慢性排斥反应，但仍有10例持续性或进行性闭塞性细支气管炎患者接受了甲氨蝶呤治疗。收集了9例至少随访6个月患者的数据。
无患者死亡。列出了8例一秒用力呼气量值下降患者的肺功能测定数据。在开始甲氨蝶呤治疗前，一秒用力呼气量较前12个月干预前最高一秒用力呼气量值的中位数下降为1.4±0.8L，即43%±17%。在6个月时，自开始甲氨蝶呤治疗起，一秒用力呼气量的中位数下降为0.1±0.2L，即3%±11%。在9个月时（n = 6），该值为0.2±0.2L，即6%±12%。在12个月时（n = 5），中位数下降为0.4±0.3L，即9%±16%。自开始甲氨蝶呤治疗后，有2例患者的一秒用力呼气量未进一步下降（1例患者有轻微但持续的改善）。在最近一次随访时，5例患者的一秒用力呼气量最多减少了10%或更少，只有1例患者未从甲氨蝶呤治疗中获得明显益处。毒性极小。
甲氨蝶呤在治疗肺移植受者闭塞性细支气管炎综合征方面是一种潜在的有前景的治疗选择。
