Effect of inhaled beclomethasone dipropionate on peroxynitrite inhibitory activity in induced sputum from asthmatic patients.
OBJECTIVE
We recently found that peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients than in normal control subjects. Current guidelines recommend inhaled corticosteroids as first-line control therapy in asthma. Therefore, this study was designed to examine the effect of inhaled beclomethasone dipropionate (BDP) on peroxynitrite inhibitory activity in induced sputum from asthmatic patients.


METHODS
Interventional study.


METHODS
University hospital.


METHODS
Twenty-one asthmatic patients and 10 age-matched, normal control subjects.


METHODS
Inflammatory indexes in induced sputum were examined in all study subjects, and peroxynitrite inhibitory activity was also assayed by monitoring rhodamine formation. For 8 weeks after the first sputum induction, BDP 400 microg bid, was administered to all asthmatic patients and sputum induction was repeated.


RESULTS
Nitrite and nitrate levels in induced sputum were significantly higher in asthmatic patients (1,121 micro mol/L [SD, 205 micro mol/L], p < 0.0001) than in normal control subjects (642 micromol/L [SD, 137 micromol/L]). In contrast, peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients (50.0% [SD, 25.7%], p < 0.0001) than in normal control subjects (93.0% [SD, 3.6%]). After 8 weeks of BDP therapy, nitrite and nitrate levels were significantly decreased (847 micromol/L [SD, 143 micromol/L], p < 0.0001) and peroxynitrite inhibitory activity was increased (73.9% [SD, 19.2%], p = 0.0005). Moreover, the increase in peroxynitrite inhibitory activity from before to after BDP therapy was significantly correlated with decrease in nitrite and nitrate levels (r = 0.79, p = 0.0004). We also found the significant relationship between increase in peroxynitrite inhibitory activity in induced sputum and increase in FEV(1) percentage of predicted after BDP therapy (r = 0.68, p = 0.0023).


CONCLUSIONS
Large amounts of peroxynitrite, which are exaggerated in acute asthma attacks, might overwhelm endogenous antioxidant defenses. However, inhaled corticosteroid therapy enhanced antioxidant activity against peroxynitrite, and therefore might reduce the susceptibility to peroxynitrite-induced injury in asthmatic airways.
Kanazawa
Hiroshi
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Nomura
Saeko
S
Hirata
Kazuto
K
Yoshikawa
Junichi
J
D000280:Administration, Inhalation; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage*; D001798:Blood Proteins / Q000378:metabolism; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D012235:Rhodamines / Q000032:analysis; D012260:Ribonucleases / Q000378:metabolism; D013183:Sputum / Q000166:cytology / Q000378:metabolism*
D000975:Antioxidants; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D009566:Nitrates; D009573:Nitrites; D012235:Rhodamines; D030421:Peroxynitrous Acid; D012260:Ribonucleases; D001507:Beclomethasone