Effect of a thromboxane A(2) Antagonist on sputum production and its physicochemical properties in patients with mild to moderate asthma

Study objective: To determine the effects of a specific thromboxane A(2) (T xA(2)) receptor antagonist, seratrodast, on asthma control and airway secre tions. Design: Multicenter, double-blind, randomized, placebo-controlled study. Patients: Forty-five patients with mild to moderate asthma who had been con tinuously expectorating sputum of > 20 g/d. Patients with a current pulmona ry infection or taking oral corticosteroids, antibiotics, or mucolytic agen ts mere excluded from the trial. Interventions: Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were as signed to receive seratrodast, 40 mg/d, or placebo for 6 weeks. Measurements and results: During the treatment period, the changes in FEV1 and peak expiratory flow (PEF) were not different between the two patient g roups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime su pplemental use of beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis, seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic viscosity (p = 0.007), and albumin concentration (p = 0.02 8), whereas it had no effect on elastic modulus or fucose concentration. Na sal clearance time of a saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031) and week 6 (p = 0.025), compared with the plac ebo group. Conclusion: Blockade of TxA(2) receptor has minimal effects on pulmonary fu nction, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.