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Original Research: COPD |

Peroxynitrite Elevation in Exhaled Breath Condensate of COPD and Its Inhibition by Fudosteine

Grace O. Osoata, PhD; Toyoyuki Hanazawa, MD; Caterina Brindicci, MD; Misako Ito, BSc; Peter J. Barnes, DM, FCCP; Sergei Kharitonov, MD; Kazuhiro Ito, PhD
Author and Funding Information

*From the Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.

Correspondence to: Kazuhiro Ito, PhD, Airway Disease Section, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK; e-mail: k.ito@imperial.ac.uk


This research was funded by Mitsubishi Pharma (Japan).

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(6):1513-1520. doi:10.1378/chest.08-2105
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Background:  Peroxynitrite (PN) formed by the reaction of nitric oxide and superoxide is a powerful oxidant/nitrosant. Nitrative stress is implicated in COPD pathogenesis, but PN has not been detected due to a short half-life (< 1 s) at physiologic condition. Instead, 3-nitrotyrosine has been measured as a footprint of PN release.

Method:  PN was measured using oxidation of 2′,7′-dichlorofluorescein (DCDHF) in exhaled breath condensate (EBC) collected in high pH and sputum cells. The PN scavenging effect was also evaluated by the same system as PN-induced bovine serum albumin (BSA) nitration.

Results:  The mean (± SD) PN levels in EBC of COPD patients (7.9 ± 3.0 nmol/L; n = 10) were significantly higher than those of healthy volunteers (2.0 ± 1.1 nmol/L; p < 0.0001; n = 8) and smokers (2.8 ± 0.9 nmol/L; p = 0.0017; n = 6). There was a good correlation between PN level and disease severity (FEV1) in COPD (p = 0.0016). Fudosteine (FDS), a unique mucolytic antioxidant, showed a stronger scavenging effect of PN than N-acetyl-cysteine on DCDHF oxidation in vitro and in sputum macrophages, and also on PN-induced BSA nitration. FDS (0.1 mmol/L) reduced PN-enhanced interleukin (IL)-1β-induced IL-8 release and restored corticosteroid sensitivity defected by PN more potently than those induced by H2O2 in A549 airway epithelial cells.

Conclusion:  This noninvasive PN measurement in EBC may be useful for monitoring airway nitrative stress in COPD. Furthermore, FDS has the potential to inhibit PN-induced events in lung by its scavenging effect.

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