Mullarkey M F, Blumenstein B A, Andrade W P, Bailey G A, Olason I, Wetzel C E
Department of Medicine, Virginia Mason Clinic, Seattle, WA 98111.
N Engl J Med. 1988 Mar 10;318(10):603-7. doi: 10.1056/NEJM198803103181004.
To test our previous observation that methotrexate reduces corticosteroid requirements of patients with severe asthma, we studied 14 patients with corticosteroid-dependent bronchial asthma in a 24-week randomized double-blind crossover trial comparing a low dosage of methotrexate (15 mg per week) with placebo. At base line the mean dosage of prednisone was 173.5 mg per week (range, 70 to 420). On the average, 36.5 percent less prednisone was required when patients received methotrexate than when they received placebo (P = 0.01). Measurement of forced vital capacity and forced expiratory volume in one second showed that there was no deterioration in the condition of patients in whom the dosage of prednisone was reduced. The patients' subjective assessment of breathing ability indicated significant improvement (P = 0.01). The adverse effects of methotrexate were limited to transient nausea in three patients and an evanescent rash in one patient. Nine patients are still receiving methotrexate 3 to 10 months after the study's conclusion. The dosages of steroids have been further reduced in each of these patients, and prednisone has been discontinued in four. We conclude from this preliminary study that the use of methotrexate allows a significant reduction in the use of corticosteroids in patients with severe asthma without deterioration of pulmonary function.
为了验证我们之前的观察结果，即甲氨蝶呤可降低重度哮喘患者对皮质类固醇的需求量，我们对14例依赖皮质类固醇的支气管哮喘患者进行了一项为期24周的随机双盲交叉试验，比较低剂量甲氨蝶呤（每周15毫克）与安慰剂的效果。基线时，泼尼松的平均剂量为每周173.5毫克（范围为70至420毫克）。平均而言，患者接受甲氨蝶呤时所需的泼尼松比接受安慰剂时少36.5%（P = 0.01）。对用力肺活量和一秒用力呼气量的测量表明，泼尼松剂量降低的患者病情并未恶化。患者对呼吸能力的主观评估显示有显著改善（P = 0.01）。甲氨蝶呤的不良反应仅限于3例患者出现短暂恶心，1例患者出现一过性皮疹。研究结束后3至10个月，9例患者仍在接受甲氨蝶呤治疗。这些患者中，每位患者的类固醇剂量都进一步降低，4例患者已停用泼尼松。我们从这项初步研究得出结论，对于重度哮喘患者，使用甲氨蝶呤可显著减少皮质类固醇的使用量，且不会导致肺功能恶化。
