Swystun V A, Bhagat R, Kalra S, Jennings B, Cockcroft D W
Royal University Hospital, University of Saskatchewan, Department of Medicine, Saskatoon, Canada.
J Allergy Clin Immunol. 1998 Sep;102(3):363-7. doi: 10.1016/s0091-6749(98)70121-6.
A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable. Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship. Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response.
Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium bromide as needed. These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70% of predicted value. A double-blind, randomized, cross-over study compared placebo and budesonide 100, 200, and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods. Methacholine PC20 was measured before and after 6 days of treatment, and allergen PC15 was measured after 7 days of treatment.
The allergen PC15 (n = 11) was significantly larger (P = .0001) for all doses of budesonide compared with placebo, but there was no significant difference between the 3 doses of budesonide, and no dose response was demonstrated. The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo (P = .024), but there was no difference between the 3 doses. There was a progressive increase in the allergen PC15 chronologically (sequence effect) that was not explained by improvement in FEV1 or airway responsiveness; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20. Statistical adjustment for sequence effect did not alter allergen PC15 statistics.
A 7-day course of budesonide administered by means of Turbuhaler at 200, 400, or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo. There was, however, no difference between the 3 doses. Therefore this method with these doses is not useful for providing assessment of relative potency.
一种评估吸入性糖皮质激素在哮喘中相对效力的简单实验室方法将很有价值。针对变应原诱发的迟发性哮喘反应的单剂量研究未能显示出有用的剂量反应关系。吸入性糖皮质激素治疗数天也会抑制变应原诱发的早发性哮喘反应。
在一个除按需使用异丙托溴铵外无需使用其他药物的季节，对12名特应性哮喘患者进行了研究。这些患者变应原和乙酰甲胆碱吸入试验呈阳性，且第一秒用力呼气容积（FEV1）大于预测值的70%。一项双盲、随机、交叉研究比较了安慰剂与通过都保装置每天两次给予100、200和400微克布地奈德，共7天，洗脱期为6天的情况。在治疗6天后测量乙酰甲胆碱PC20，在治疗7天后测量变应原PC15。
与安慰剂相比，所有剂量布地奈德的变应原PC15（n = 11）均显著增大（P = 0.0001），但3种剂量的布地奈德之间无显著差异，也未显示出剂量反应。与安慰剂相比，所有布地奈德治疗后的乙酰甲胆碱PC20均显著增大（P = 0.024），但3种剂量之间无差异。变应原PC15按时间顺序逐渐增加（序列效应），这无法用FEV1或气道反应性的改善来解释；FEV1以及治疗前或治疗后的乙酰甲胆碱PC20均未出现序列效应。对序列效应进行统计调整并未改变变应原PC15的统计结果。
与安慰剂相比，每天通过都保装置给予200、400或800微克布地奈德，疗程7天，可显著抑制变应原诱发的早发性哮喘反应。然而，这3种剂量之间并无差异。因此，这种方法和这些剂量对于评估相对效力并无用处。
