Cockcroft D W, Keshmiri M, Murdock K Y, Gore B C
Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
Ann Allergy. 1992 Mar;68(3):245-50.
Allergen-induced increase in airway responsiveness to histamine or methacholine provides a useful model for investigation of prophylactic or "antiinflammatory" asthma treatments. This can be inhibited by corticosteroids or by sodium cromoglycate but not by beta agonists or by theophylline. A single-blind, crossover, random-order trial was conducted to compare ketotifen, clemastine, and placebo in six atopic subjects undergoing allergen inhalation tests. Ketotifen, 2 mg; clemastine, 1 mg; and placebo one tablet were administered twice daily for four days (eight doses) up to and including one hour before allergen inhalation. None of the three produced a significant reduction in the allergen-induced early or late asthmatic responses, or in the allergen-induced fall in methacholine PC20. There was a subtle nonsignificant suggestion of a reduction in the early portion of the early asthmatic response induced by both ketotifen and clemastine. Both ketotifen and clemastine produced a similar 8-fold inhibition of histamine skin test endpoint indicating equal systemic H1 blocking effect at the time of allergen inhalation. Sodium cromoglycate, 10 mg, single dose, by metered dose inhaler ten minutes before allergen challenge, added as an unblinded "positive control", inhibitory effects on the allergen-induced late and presumed inflammatory sequelae. It is possible that longer treatment periods (several weeks or months) might prove effective.
变应原诱导的气道对组胺或乙酰甲胆碱反应性增加为研究预防性或“抗炎性”哮喘治疗提供了一个有用的模型。这可被皮质类固醇或色甘酸钠抑制，但不能被β受体激动剂或茶碱抑制。进行了一项单盲、交叉、随机顺序试验，以比较酮替芬、氯马斯汀和安慰剂对6名接受变应原吸入试验的特应性受试者的作用。酮替芬2毫克、氯马斯汀1毫克和安慰剂一片，每天服用两次，共四天（八剂），直至变应原吸入前一小时，包括该时间点。这三种药物均未使变应原诱导的早期或晚期哮喘反应或变应原诱导的乙酰甲胆碱PC20下降显著降低。酮替芬和氯马斯汀对早期哮喘反应的早期部分有轻微但不显著的降低趋势。酮替芬和氯马斯汀对组胺皮肤试验终点均产生了相似的8倍抑制作用，表明在变应原吸入时全身H1阻断作用相同。在变应原激发前10分钟，通过定量吸入器给予10毫克色甘酸钠单剂量作为非盲法“阳性对照”，其对变应原诱导的晚期反应及推测的炎症后遗症有抑制作用。较长的治疗期（数周或数月）可能证明是有效的。
