Aizawa H, Shigyo M, Nogami H, Hirose T, Hara N
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Japan.
Chest. 1996 Feb;109(2):338-42. doi: 10.1378/chest.109.2.338.
Thromboxane A2 (TXA2) is reported to induce bronchial hyperresponsiveness along with the well-documented bronchoconstrictor action on smooth muscles. We examined the effect of the TXA2 antagonist, BAY u3405, on bronchial hyperresponsiveness to methacholine (MCh) in asthmatics.
Twelve adult asthmatics were studied in a randomized, double-blind, placebo-controlled, crossover fashion.
Following a 2-week run-in period, the subjects were administered 75 mg of BAY u3405 or placebo orally, twice a day for 2 weeks each in a crossover design, interposing a 2-week washout period. Bronchial hyperresponsiveness was measured by the astograph method. Briefly, the respiratory resistance (Rrs) was measured by the forced oscillation method during continuous inhalation of MCh in stepwise incremental concentrations, until Rrs reached twice the baseline value. Bronchial hyperresponsiveness was evaluated as the minimum cumulative dose (Dmin) of MCh that induced an increase in Rrs. Dmin was calculated so that 1 U of Dmin equals to 1 min of inhalation of aerosol solution at 1.0 mg/mL during quiet breathing.
Three subjects were withdrawn from the evaluation because they had asthmatic attacks or wheezing during the study. The Dmin value of 0.533 U (GSEM 1.675) after the BAY u3405 treatment was significantly greater than that of 0.135 U (GSEM 1.969) after the placebo treatment (p = 0.0139). There were no safety concerns in either treatment group.
We conclude that BAY u3405 may be a useful drug for attenuating bronchial hyperresponsiveness in bronchial asthma.
据报道，血栓素A2（TXA2）可诱发支气管高反应性，同时对平滑肌具有已被充分证明的支气管收缩作用。我们研究了TXA2拮抗剂BAY u3405对哮喘患者支气管对乙酰甲胆碱（MCh）高反应性的影响。
12名成年哮喘患者以随机、双盲、安慰剂对照、交叉方式进行研究。
在为期2周的导入期后，受试者采用交叉设计，口服75 mg BAY u3405或安慰剂，每天两次，各服用2周，中间间隔2周的洗脱期。采用哮喘描记法测量支气管高反应性。简要地说，在逐步递增浓度持续吸入MCh期间，通过强迫振荡法测量呼吸阻力（Rrs），直至Rrs达到基线值的两倍。支气管高反应性以诱发Rrs增加的MCh最小累积剂量（Dmin）进行评估。计算Dmin时，使1单位Dmin等于安静呼吸时吸入1.0 mg/mL气雾剂溶液1分钟。
3名受试者因在研究期间发生哮喘发作或喘息而退出评估。BAY u3405治疗后的Dmin值为0.533单位（GSEM 1.675），显著高于安慰剂治疗后的0.135单位（GSEM 1.969）（p = 0.0139）。两个治疗组均无安全性问题。
我们得出结论，BAY u3405可能是一种用于减轻支气管哮喘患者支气管高反应性的有效药物。
