Luijk B, Kempsford R D, Wright A M, Zanen P, Lammers J W J
Dept of Pulmonary Diseases, Heart-Lung Center Utrecht, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Eur Respir J. 2004 Apr;23(4):559-64. doi: 10.1183/09031936.04.00043504.
Airway hyperresponsiveness induced by adenosine-5'-monophosphate (AMP) is regarded as a reliable model for allergic asthma and for the evaluation of anti-asthmatic drugs. Single-dose inhaled corticosteroids (ICS) are known to be protective in this model, but the duration of action of these drugs in this model has never been studied. The duration of ICS protection was determined by administration of single-dose fluticasone propionate (FP; 1,000 micrograms) up to 26 h before AMP challenge. A randomised, double-blind, placebo-controlled, four-way crossover study was performed in 13 mild asthmatics (mean +/- SD predicted forced expiratory volume in one second (FEV1) 98 +/- 7%). Each subject received placebo and FP (at 26, 14 or 2 h prior to the AMP challenge). Furthermore, the marker exhaled nitric oxide (eNO) was studied after administration at these time points to investigate whether eNO also demonstrates the duration of action of ICS. The doubling concentrations difference (DCD) of AMP causing a 20% fall in FEV1, when FP was administered 26, 14 or 2 h prior to challenge, was significantly increased as compared with placebo: DCD (95% confidence interval) at 26 h, 0.73 (0.20-1.26), p = 0.008; 14 h, 1.50 (0.99-2.01), p < 0.001; and 2 h, 2.89 (2.37-3.40), p < 0.001. However, eNO was not significantly affected at these time points. In conclusion, a single dose of 1,000 micrograms inhaled fluticasone propionate protects against adenosine-5'-monophosphate airway hyperresponsiveness up to 26 h after dosing. This study suggests that adenosine-5'-monophosphate challenge can be used as a sensitive marker to study the duration of action of inhaled corticosteroids.
由5'-单磷酸腺苷（AMP）诱导的气道高反应性被视为过敏性哮喘以及抗哮喘药物评估的可靠模型。已知单剂量吸入性糖皮质激素（ICS）在此模型中具有保护作用，但这些药物在此模型中的作用持续时间从未被研究过。通过在AMP激发前长达26小时给予单剂量丙酸氟替卡松（FP；1000微克）来确定ICS保护的持续时间。对13名轻度哮喘患者（预测一秒用力呼气量（FEV1）平均±标准差为98±7%）进行了一项随机、双盲、安慰剂对照、四交叉研究。每位受试者接受安慰剂和FP（在AMP激发前26、14或2小时）。此外，在这些时间点给药后研究呼出一氧化氮（eNO）标志物，以调查eNO是否也能体现ICS的作用持续时间。与安慰剂相比，在激发前26、14或2小时给予FP时，导致FEV1下降20%的AMP加倍浓度差异（DCD）显著增加：26小时时DCD（95%置信区间）为0.73（0.20 - 1.26），p = 0.008；14小时时为1.50（0.99 - 2.01），p < 0.001；2小时时为2.89（2.37 - 3.40），p < 0.001。然而，在这些时间点eNO未受到显著影响。总之，单剂量1000微克吸入性丙酸氟替卡松在给药后长达26小时可预防AMP诱导的气道高反应性。本研究表明，AMP激发可作为研究吸入性糖皮质激素作用持续时间的敏感标志物。
