Merland N, Cartier A, L'Archevêque J, Ghezzo H, Malo J L
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Quebec, Canada.
Am Rev Respir Dis. 1988 Jun;137(6):1304-8. doi: 10.1164/ajrccm/137.6.1304.
The aim of this study was to evaluate the effect of a sustained-release theophylline preparation on bronchial responsiveness to cold dry air inhalation in asthmatic subjects. Sixteen adult subjects with asthma in a clinical steady state underwent 3 isocapnic cold air challenges on 3 consecutive days at a time when they had not received oral theophylline medication over the past 3 days. The dose of cold air causing a 20% (PD20) fall in FEV1 was obtained from each subject's dose-response curve. Subjects were then administered active or placebo sustained-release theophylline preparations according to a double-blind, randomized, two-treatment crossover design. Medication was given for a minimum of 3 consecutive days. PD20 was reassessed on 4 different days, 3 to 4 h after receiving active or placebo medication (two visits for each medication). We found a significant bronchodilator effect of theophylline as compared to the placebo (mean +/- SD differences in changes of FEV1 of 8.8 +/- 1.9%). We also documented a significant blocking effect of the active medication as opposed to the placebo on PD20 (p = 0.01). This difference (mean = 0.18 on the loge scale) was statistically beyond the intraindividual between-day variability observed on the 3 control days (p less than 0.001) but was physiologically minimal. This blocking effect was also partially related to changes in airway caliber. We conclude that theophylline showed a blocking effect on bronchial responsiveness to dry cold air, which was physiologically minimal and was partially related to changes in airway caliber.
本研究的目的是评估缓释茶碱制剂对哮喘患者支气管对吸入冷干空气反应性的影响。16名处于临床稳定状态的成年哮喘患者，在过去3天未接受口服茶碱药物治疗的情况下，连续3天接受3次等碳酸冷空气激发试验。从每个受试者的剂量反应曲线中获取导致第一秒用力呼气容积（FEV1）下降20%（PD20）的冷空气剂量。然后，根据双盲、随机、双治疗交叉设计，给受试者服用活性或安慰剂缓释茶碱制剂。药物至少连续服用3天。在接受活性或安慰剂药物治疗后3至4小时的4个不同日子重新评估PD20（每种药物各访视两次）。我们发现，与安慰剂相比，茶碱有显著的支气管舒张作用（FEV1变化的平均±标准差差异为8.8±1.9%）。我们还记录到，与安慰剂相比，活性药物对PD20有显著的阻断作用（p = 0.01）。这种差异（对数尺度上的平均值 = 0.18）在统计学上超出了在3个对照日观察到的个体内日间变异性（p < 0.001），但在生理上是最小的。这种阻断作用也部分与气道管径的变化有关。我们得出结论，茶碱对支气管对干冷空气的反应性有阻断作用，这种作用在生理上是最小的，且部分与气道管径的变化有关。
