Involvement of thromboxane A2 in bronchial hyperresponsiveness of asthma. Kanazawa Asthma Research Group

It has been considered that thromboxane A2 (TXA2) is involved in the development of bronchial hyperresponsiveness (BHR), a characteristic feature of asthma. To ensure the involvement of TXA2 in BHR of asthma, effects of a 1-week treatment with two orally active TXA2 antagonists, BAY u 3405 and S-1452, on BHR were examined in 10 and 13 patients with stable asthma, respectively, in two consecutive double-blinded, randomized, placebo-controlled, two-phase crossover studies. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) with BAY u 3405 (0.78 (GSEM, 1.50) mg/ml) was significantly greater than the value with placebo (0.65 (GSEM, 1.46) mg/ml) (ratio 1.23 times, 95% CI 1.01 to 1.46: P = 0.0401). PC20-FEV1 was also significantly increased with S-1452 (0.43 (GSEM, 1.39) mg/ml) compared with placebo (0.29 (GSEM, 1.27) mg/ml) (ratio 1.75 times, 95% CI 1.05 to 2.45: P = 0.0189). Baseline pulmonary function was not altered by these treatments. These results may ensure that TXA2 is significantly involved in the BHR of asthma while the degree of contribution may be small.