Bardin P G, Fraenkel D J, Beasley R W
Immunopharmacology Group, University Medicine, Southampton General Hospital, England.
Drug Saf. 1993 Sep;9(3):151-5. doi: 10.2165/00002018-199309030-00002.
The inflammatory process underlying bronchial asthma is well established and has prompted clinical interest in nonsteroidal anti-inflammatory forms of treatment. Although unproven, it has been suggested that effective treatment of allergic inflammation may prevent long term consequences of asthma and avert deterioration in pulmonary function. Methotrexate has potent anti-inflammatory actions, even at low doses, and was judged to be a suitable candidate drug for asthma treatment if it could demonstrate an acceptable tolerability profile. Low dose methotrexate has been investigated in both noncomparative studies and in placebo-controlled studies of severe asthma. In general, such studies have suggested that methotrexate may have steroid-sparing benefits coupled to generally mild adverse events; although adverse effects were not of a serious nature they were observed in up to one-third of patients. Rare but potentially life-threatening adverse effects involving the pulmonary, hepatic and haematological systems remain of particular concern. Methotrexate should therefore be considered as an adjunct to high dose inhaled corticosteroids in patients who require more than 10mg of prednisolone daily, and who experience severe and unacceptable steroid-related adverse effects. Treatment should only be initiated by physicians with experience in the use of the drug, and the relevant safety parameters should be closely monitored.
支气管哮喘潜在的炎症过程已得到充分证实，并引发了临床上对非甾体抗炎治疗形式的关注。尽管未经证实，但有人提出，有效治疗过敏性炎症可能预防哮喘的长期后果，并避免肺功能恶化。甲氨蝶呤即使在低剂量时也具有强大的抗炎作用，如果它能表现出可接受的耐受性，就被认为是一种适合治疗哮喘的候选药物。低剂量甲氨蝶呤已在非对照研究和重度哮喘的安慰剂对照研究中进行了调查。一般来说，这些研究表明，甲氨蝶呤可能具有节省类固醇的益处，且通常不良反应较轻；尽管不良反应不严重，但在多达三分之一的患者中观察到了这些不良反应。涉及肺、肝和血液系统的罕见但可能危及生命的不良反应仍然是特别令人担忧的问题。因此，对于每天需要超过10毫克泼尼松龙且出现严重且无法接受的类固醇相关不良反应的患者，甲氨蝶呤应被视为高剂量吸入性糖皮质激素的辅助药物。治疗应由有该药物使用经验的医生启动，并且应密切监测相关的安全参数。
