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Effect of a Thromboxane A₂ Antagonist on Sputum Production and Its Physicochemical Properties in Patients With Mild to Moderate Asthma^*

^* From the First Department of Medicine (Drs. Tamaoki and Nagai), Tokyo Women’s Medical University School of Medicine; Department of Respirology (Dr. Isono), Kurihashi-Saiseikai Hospital; Department of Medicine (Dr. Nagano), Hamacho Center Clinic; Department of Respiratory Medicine (Dr. Kondo), Ayase-Minshu Hospital; Department of Medicine (Dr. Nakata), Airi Hospital, Tokyo, Japan.

Correspondence to: Jun Tamaoki, MD, FCCP, Tokyo Women’s Medical University School of Medicine, 8–1 Kawada-Cho, Shinjuku, Tokyo 162-8666, Japan; e-mail: jtamaoki{at}xc4.so-net.ne.jp

Study objective: To determine the effects of a specific thromboxane A₂ (TxA₂) receptor antagonist, seratrodast, on asthma control and airway secretions.

Design: Multicenter, double-blind, randomized, placebo-controlled study.

Patients: Forty-five patients with mild to moderate asthma who had been continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary infection or taking oral corticosteroids, antibiotics, or mucolytic agents were excluded from the trial.

Interventions: Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were assigned 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 groups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of ß₂-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 = 0.028), whereas it had no effect on elastic modulus or fucose concentration. Nasal 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 placebo group.

Conclusion: Blockade of TxA₂ receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.

Key Words: airway secretion • elasticity • mucociliary clearance • thromboxane • vascular leakage • viscosity

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