Peccini F, Dottorini M L, Casucci G, Mezzasoma A M, Sorbini C A, Tantucci C
Divisione di Medicina Interna of the Hospital of Gubbio, Perugia, Italy.
Monaldi Arch Chest Dis. 1997 Apr;52(2):130-7.
In a randomized, double-blind, placebo-controlled study, the acute and long-term effects of the reduction of thromboxane A2 (TxA2) synthesis on airway sensitivity and maximal airway narrowing in response to methacholine was evaluated in 12 subjects with mild-to-moderate stable asthma, using imidazole salycilate (IS), an anti-inflammatory drug which selectively inhibits the TxA2 synthetase. Dose-response curves with methacholine (MCh) were performed in basal conditions (baseline); 1-1.5 h after administration of 1,500 mg of IS or placebo (acute); at 15 and 30 days of treatment with 750 mg t.i.d. of IS or placebo; and after a 2 week period of run-off (45 days). The serum levels of thromboxane B2 (TxB2) were measured at the same time points, except after acute administration, in five patients from each group. Baseline forced expiratory volume in one second (FEV1) was 78 +/- 7 and 85 +/- 8% of predicted in the IS and control group, respectively (NS). Throughout the study FEV1 remained unchanged in both groups, indicating that IS did not caused substantial modification of resting bronchial calibre. The initial provocative dose of methacholine causing a 20% fall in FEV1 (PD20) amounted to 27.0 +/- 1.5 micrograms in the IS group and 41.7 +/- 1.5 micrograms in the control group (geometric mean +/- GSEM) (NS). Despite a reduction of TxB2 serum levels with IS vs placebo at 15 days (24.9 +/- 8.5 vs 45.5 +/- 3.4 pg.mL-1; p < 0.05) and 30 days (27.0 +/- 6.3 vs 45.0 + 3.2 pg.mL-1; p < 0.05), MCh-induced bronchoconstriction, evaluated either as PD20 or maximal airway narrowing, did not change significantly during active treatment compared to placebo. These results show that prolonged reduction of thromboxane A2 synthesis does not improve airway sensitivity and limit maximal bronchoconstriction in asthmatic subjects, suggesting that thromboxane A2 per se does not play a substantial role in the pathogenesis of the airway hyperresponsiveness in human asthma.
在一项随机、双盲、安慰剂对照研究中，使用咪唑水杨酸酯（IS）（一种选择性抑制血栓素A2合成酶的抗炎药物），对12例轻至中度稳定型哮喘患者进行了研究，以评估减少血栓素A2（TxA2）合成对气道敏感性和对乙酰甲胆碱反应时最大气道狭窄的急性和长期影响。在基础条件下（基线）、给予1500mg IS或安慰剂后1-1.5小时（急性）、用750mg IS或安慰剂每日三次治疗15天和30天时，以及在停药2周（45天）后，进行了乙酰甲胆碱（MCh）的剂量反应曲线测定。除急性给药后外，在每个组的5例患者中，在相同时间点测量血栓素B2（TxB2）的血清水平。IS组和对照组的一秒用力呼气容积（FEV1）基线分别为预测值的78±7%和85±8%（无显著性差异）。在整个研究过程中，两组的FEV1均保持不变，表明IS并未引起静息支气管口径的实质性改变。在IS组中，引起FEV1下降20%的初始乙酰甲胆碱激发剂量（PD20）为27.0±1.5μg，在对照组中为41.7±1.5μg（几何平均值±几何标准误）（无显著性差异）。尽管在15天（24.9±8.5对45.5±3.4pg.mL-1；p<0.05）和30天（27.0±6.3对45.0+3.2pg.mL-1；p<0.05）时，与安慰剂相比，IS使TxB2血清水平降低，但与安慰剂相比，在积极治疗期间，以PD20或最大气道狭窄评估的MCh诱导的支气管收缩并未显著改变。这些结果表明，长期减少血栓素A2合成并不能改善哮喘患者的气道敏感性，也不能限制最大支气管收缩，提示血栓素A2本身在人类哮喘气道高反应性的发病机制中并不起重要作用。
