The effect of seratrodast on eosinophil cationic protein and symptoms in asthmatics.
Thromboxane A2 (TXA2), an arachidonate derivative, is a potent bronchoconstrictor; therefore, blocking TXA2 should attenuate airway narrowing. Seratrodast, a TXA2 receptor antagonist, is expected to be a potent antiasthmatic. It was reported that seratrodast reduced bronchial hyperresponsiveness. However, it is controversial whether it reduces airway inflammation. We studied some additional effects of oral seratrodast to inhaled corticosteroids on 10 adult asthmatics in an open-label, crossover design study. Eosinophil cationic protein (ECP) levels in serum and sputum, peak expiratory flow rate (PEF), clinical symptoms, and airway responsiveness were evaluated. Clinical symptom scores were improved by administration of seratrodast (p < 0.05). The addition of seratrodast to asthmatic patients significantly improved mean PEF (p < 0.05). In addition, withdrawal of seratrodast resulted in deterioration of PEF. Airway hyperresponsiveness to acetylcholine measured by Astograph was improved by administration of seratrodast (p < 0.01), and returned to the level of "run-in period" after withdrawal. Administration of seratrodast decreased the concentration of ECP in sputum significantly (p < 0.05), and sputum ECP significantly increased again after withdrawal of (p < 0.05). These results suggest that seratrodast improves clinical symptoms andairway hyperresponsiveness by reducing airway inflammation. Seratrodast may be useful as an anti-inflammatory agent and beneficial when added to inhaled corticosteroids in the treatment of bronchial asthma.
Fukuoka
Toshihiko
T
The Pulmonary Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Miyake
Shuji
S
Umino
Takeshi
T
Inase
Naohiko
N
Tojo
Naoko
N
Yoshizawa
Yasuyuki
Y
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016227:Benzoquinones / Q000627:therapeutic use*; D001798:Blood Proteins / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D018592:Cross-Over Studies; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D010366:Peak Expiratory Flow Rate; D012260:Ribonucleases; D013183:Sputum / Q000737:chemistry; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D018927:Anti-Asthmatic Agents; D016227:Benzoquinones; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D006538:Heptanoic Acids; D018836:Inflammation Mediators; C060230:seratrodast; D013928:Thromboxane A2; D012260:Ribonucleases