Thomson N C, Roberts R, Bandouvakis J, Newball H, Hargreave F E
J Allergy Clin Immunol. 1981 Nov;68(5):392-8. doi: 10.1016/0091-6749(81)90138-x.
We examined bronchial responsiveness to prostaglandin (PG) F2 alpha to determine its applicability in clinical practice and to compare it with bronchial responsiveness to the pharmacologically dissimilar agent, methacholine. Inhalation tests with two fold increasing concentrations of the two agents were carried out in 19 asthmatic and four normal subjects. The results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 sec (PC20). The range of concentrations required to determine the PC20 was greater with PGF2 alpha (0.0001 to less than 5 mg/ml) than that with methacholine (0.07 to 30.96 mg/ml). Side effects of cough, retrosternal irritation, and expectoration of sputum were more frequent after PGF2 alpha. Repeat measurements in the same subjects showed that response to PGF2 alpha were as highly reproducible (r = 0.98, p less than 0.001) as previously reported with methacholine, and there was a cumulative dose effect (p less than 0.001). PC20PGF2 alpha correlated with PC20 methacholine (r = 0.5, p less than 0.01), but to a lesser degree than was previously demonstrated between histamine and methacholine. The poorer correlation was explained by the results of four subjects tolerant to PGF2 alpha relative to methacholine, three of whom were aspirin (ASA) intolerant; the correlation was much stronger when these subjects were excluded from analysis (r = 0.91, p less than 0.001). The results suggests that (1) PGF2 alpha is not a suitable agent to use in clinical practice to measure nonspecific bronchial responsiveness because of the wide dose range and unpleasant side effects, (2) the bronchial responsiveness of different individuals to PGF2 alpha and methacholine is usually well correlated and is thus unrelated to specific receptor activity, and (3) there is a relative reduction in responsiveness to PGF2 alpha in some asthmatics, particularly those with ASA intolerance.
我们检测了支气管对前列腺素(PG)F2α的反应性,以确定其在临床实践中的适用性,并将其与支气管对药理性质不同的药物乙酰甲胆碱的反应性进行比较。对19名哮喘患者和4名正常受试者进行了两种药物浓度成倍增加的吸入试验。结果以引起一秒用力呼气量下降20%的激发浓度(PC20)表示。与乙酰甲胆碱(0.07至30.96mg/ml)相比,确定PGF2α的PC20所需的浓度范围更大(0.0001至小于5mg/ml)。PGF2α后咳嗽、胸骨后刺激和咳痰等副作用更常见。同一受试者的重复测量显示,对PGF2α的反应与之前报道的乙酰甲胆碱一样具有高度可重复性(r = 0.98,p < 0.001),并且存在累积剂量效应(p < 0.001)。PC20PGF2α与PC20乙酰甲胆碱相关(r = 0.5,p < 0.01),但相关性程度低于组胺与乙酰甲胆碱之间先前显示的程度。相关性较差是由4名相对于乙酰甲胆碱对PGF2α耐受的受试者的结果所解释的,其中3名对阿司匹林(ASA)不耐受;当将这些受试者排除在分析之外时,相关性更强(r = 0.91,p < 0.001)。结果表明:(1)由于剂量范围广和副作用令人不适,PGF2α不是临床实践中用于测量非特异性支气管反应性的合适药物;(2)不同个体对PGF2α和乙酰甲胆碱的支气管反应性通常相关性良好,因此与特定受体活性无关;(3)一些哮喘患者,尤其是那些对ASA不耐受的患者,对PGF2α的反应性相对降低。