Effect of thromboxane A2 synthetase inhibitor, OKY-046, on sputum in chronic bronchitis and diffuse panbronchiolitis

The mechanisms of excessive sputum production are only partially understood. We speculated that a selective thromboxane (Tx) A2 synthetase inhibitor, OKY-046, now used in the treatment of asthma in Japan, could decrease excess sputum production in patients with chronic airways disease. To test this hypothesis, we carried out a double-blind, placebo-controlled study of the effects of OKY-046, administered orally at 400 mg.day-1, on the sputum of patients with chronic bronchitis and patients with diffuse panbronchiolitis. Patients treated with OKY-046 showed a significant decrease (22%) in sputum volume after 1 month, and a 39% decrease after 3 months. Although the rheological properties of the sputum and the concentrations of fucose and immunoglobulin (Ig) A in the sputum remained unchanged, significant decreases were observed in the concentrations of total protein, albumin, sialic acid and phospholipid. Since albumin and fucose are chemical markers of plasma exudation and mucus secretion, respectively, whilst sialic acid and phospholipid are derived both from serum and mucus, our results indicate that this TxA2 synthetase inhibitor reduced sputum volume by inhibiting microvascular leakage in the airway. OKY-046 may, therefore, be of value in the treatment of chronic bronchitis and diffuse panbronchiolitis.