Effect of a thromboxane A(2) antagonist on sputum production and its physicochemical properties in patients with mild to moderate asthma.
OBJECTIVE
To determine the effects of a specific thromboxane A(2) (TxA(2)) receptor antagonist, seratrodast, on asthma control and airway secretions.


METHODS
Multicenter, double-blind, randomized, placebo-controlled study.


METHODS
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.


METHODS
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.


RESULTS
During the treatment period, the changes in FEV(1) 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 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 = 0.028), 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.


CONCLUSIONS
Blockade of TxA(2) receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Department of Respirology, Tokyo, Japan. jtamaoki@xc4.so-net.ne.jp
Kondo
M
M
Nakata
J
J
Nagano
Y
Y
Isono
K
K
Nagai
A
A
D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology*; D016227:Benzoquinones / Q000494:pharmacology*; D004311:Double-Blind Method; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D015656:Respiratory Mechanics; D013183:Sputum / Q000737:chemistry / Q000378:metabolism*; D014783:Viscosity
D018927:Anti-Asthmatic Agents; D016227:Benzoquinones; D006538:Heptanoic Acids; C060230:seratrodast