Document Detail

Effect of inhaled beclomethasone dipropionate on peroxynitrite inhibitory activity in induced sputum from asthmatic patients.
MedLine Citation:
PMID:  14605045     Owner:  NLM     Status:  MEDLINE    
STUDY OBJECTIVES: 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. DESIGN: Interventional study. SETTING: University hospital. PATIENTS: Twenty-one asthmatic patients and 10 age-matched, normal control subjects. INTERVENTIONS: 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. MEASUREMENTS AND 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.
Hiroshi Kanazawa; Saeko Nomura; Kazuto Hirata; Junichi Yoshikawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chest     Volume:  124     ISSN:  0012-3692     ISO Abbreviation:  Chest     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-07     Completed Date:  2003-12-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1755-61     Citation Subset:  AIM; IM    
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
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MeSH Terms
Administration, Inhalation
Antioxidants / metabolism
Asthma / drug therapy,  metabolism*,  physiopathology
Beclomethasone / administration & dosage*
Blood Proteins / metabolism
Eosinophil Granule Proteins
Forced Expiratory Volume
Glucocorticoids / administration & dosage*
Nitrates / metabolism
Nitrites / metabolism
Peroxynitrous Acid / metabolism*
Rhodamines / analysis
Ribonucleases / metabolism
Sputum / cytology,  metabolism*
Reg. No./Substance:
0/Antioxidants; 0/Blood Proteins; 0/Eosinophil Granule Proteins; 0/Glucocorticoids; 0/Nitrates; 0/Nitrites; 0/Rhodamines; 14691-52-2/Peroxynitrous Acid; 4419-39-0/Beclomethasone; EC 3.1.-/Ribonucleases
Comment In:
Chest. 2003 Nov;124(5):1630-2   [PMID:  14605024 ]

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