Involvement of thromboxane A2 in bronchial hyperresponsiveness of asthma

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 FEV, (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.