Hydrogen Peroxide in Exhaled Breath Condensate in Patients with Asthma

Teng, Yue; Sun, Peili; Zhang, Jingying; Yu, Rongbin; Bai, Jianling; Yao, Xin; Huang, Mao; Adcock, Ian M.; Barnes, Peter J.

doi:10.1378/chest.10-2816

Cited by 62 publications

(48 citation statements)

References 49 publications

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“…There may be accumulation of H 2 O 2 at the site of inflammation in asthma, in part related to the low level of catalase activity (16). In support that catalytic inactivation may be relevant to the pathophysiologic state of asthma, numerous studies report that high levels of O 2 c -and H 2 O 2 are generated in the airways and found in the exhaled breath condensate of asthmatic patients, particularly during asthma exacerbations (Supplementary Table S2) (41). To our knowledge, this is the first report which identifies that a more reducing intracellular environment causes disulfide bond disruption in CuZnSOD, making the protein susceptible to oxidation inactivation.…”

Section: Discussionmentioning

confidence: 99%

“…Spontaneous asthma attacks and models of experimental antigen challenge are associated with immediate release of high levels of reactive oxygen species (ROS) (11), for example, superoxide (O 2 c -) and hydrogen peroxide (H 2 O 2 ), which persist throughout the late asthmatic response (3,4,8,41). Experimental models of asthma and clinical studies of asthma indicate a mechanistic link between intermittent excessive oxidative processes and the progressive airway injury and remodeling, which defines severe asthma pathology (39).…”

Section: Introductionmentioning

confidence: 99%

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Disulfide Bond As a Switch for Copper-Zinc Superoxide Dismutase Activity in Asthma

Ghosh

Willard

Comhair

et al. 2013

Antioxidants & Redox Signaling

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Aim: Loss of superoxide dismutase (SOD) activity is a defining biochemical feature of asthma. However, mechanisms for the reduced activity are unknown. We hypothesized that loss of asthmatic SOD activity is due to greater susceptibility to oxidative inactivation. Result: Activity assays of blood samples from asthmatics and healthy controls revealed impaired dismutase activity of copper-zinc SOD (CuZnSOD) in asthma. CuZnSOD purified from erythrocytes or airway epithelial cells from asthmatic was highly susceptible to oxidative inactivation. Proteomic analyses identified that inactivation was related to oxidation of cysteine 146 (C146), which is usually disulfide bonded to C57. The susceptibility of cysteines pointed to an alteration in protein structure, which is likely related to the loss of disulfide bond. We speculated that a shift to greater intracellular reducing potential might account for the change. Strikingly, measures of reduced and oxidized glutathione confirmed greater reducing intracellular state in asthma, compared with controls. Similarly, greater free thiol in CuZnSOD was confirmed by *2-fold greater N-ethylmaleimide binding to C146 in asthma as compared with controls. Innovation: Greater reducing potential under a chronic inflammatory state of asthma, thus, leads to susceptibility of CuZnSOD to oxidative inactivation due to cleavage of C57-C146 disulfide bond and exposure of usually unavailable cysteines. Conclusion: Vulnerability of CuZnSOD influenced by redox likely amplifies injury and inflammation during acute asthma attacks when reactive oxygen species are explosively generated. Overall, this study identifies a new paradigm for understanding the chemical basis of inflammation, in which redox regulation of thiol availability dictates protein susceptibility to environmental and endogenously generated reactive species. Antioxid. Redox Signal. 18,[412][413][414][415][416][417][418][419][420][421][422][423]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disulfide Bond As a Switch for Copper-Zinc Superoxide Dismutase Activity in Asthma

Ghosh

Willard

Comhair

et al. 2013

Antioxidants & Redox Signaling

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“…A recent study has shown that H 2 O 2 values in adults with asthma are indeed higher than in the healthy population; they increase in accordance with the severity of the condition, and also reflect the administration of inhaled corticosteroid treatment. Although a nonsignificant trend was found, H 2 O 2 levels did not seem to be affected by asthma control [107]. In fact, another recent study found no significant correlations between H 2 O 2 levels and scores on the Asthma Control Test or FeNO level in stable asthma patients [108].…”

Section: Exhaled Breath Condensatementioning

confidence: 99%

Usefulness of Noninvasive Methods for the Study of Bronchial Inflammation in the Control of Patients with Asthma

Muñoz

Bustamante²,

López-Campos³

et al. 2015

Int Arch Allergy Immunol

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Bronchial asthma is one of the most prevalent respiratory conditions. Although it is defined as an inflammatory disease, the current guidelines for both diagnosis and follow-up of patients are based only on clinical and lung function parameters. Current research is focused on finding markers that can accurately predict future risk, and on assessing the ability of these markers to guide medical treatment and thus improve prognosis. The use of noninvasive methods to study airway inflammation is gaining increasing support. The study of eosinophils in induced sputum has proved useful for the diagnosis of asthma; however, its clinical implementation is complex. Some studies have shown that the measurement of exhaled nitric oxide (FeNO) may also be useful to establish disease phenotypes and improve control. Others have found that the measurement of pH and certain markers of oxidative stress, cytokines and prostanoids in exhaled breath condensate (EBC) may also be useful as well as the measurement of the temperature of exhaled breath and the analysis of volatile organic compounds (VOCs). In conclusion, since asthma is an inflammatory disease, it seems appropriate to try to control it through the study of airway inflammation using noninvasive methods. In this regard, the analysis of induced sputum cells has proved very useful, although the clinical implementation of this technique seems difficult. Other techniques such as temperature measurement, the analysis of FeNO, the analysis of the VOCs in exhaled breath, or the study of certain biomarkers in EBC require further study in order to determine their clinical applicability.

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“…H 2 O 2 is volatile and readily equilibrates with air, thus its presence can be easily detected in EBC as a marker of pulmonary inflammation and oxidative stress. Compared to healthy subjects, EBC H 2 O 2 has been shown to be significantly increased in patients with asthma [ 92 ], COPD [ 110 ], bronchiectasis [ 111 ], acute respiratory distress syndrome [ 112 ], interstitial lung disease [ 113 ] and cardiothoracic surgery [ 114 ], but not cystic fibrosis [ 115 ].…”

Section: Biomarkers In Ebc Hydrogen Peroxidementioning

confidence: 99%

Exhaled breath condensate: a comprehensive update

Ahmadzai

Huang²,

Hettiarachchi³

et al. 2013

Clinical Chemistry and Laboratory Medicine

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Since the late 1990s, a surge in interest in the analysis of exhaled breath condensate (EBC) resulted in the American Thoracic Society and European Respiratory Society (ATS/ERS) organising a Task Force in 2001 to develop guidelines on EBC collection and measurement of biomarkers. This Task Force published their guidelines in 2005 based on literature and expert opinions at that time, and multiple shortcomings and knowledge deficits were also identified. The clinical application of EBC collection and its biomarkers are currently still limited by several of these knowledge gaps, hence further guidelines for standardisation are required to ensure external validity. Using related articles produced since the publication of the ATS/ERS Task Force report, this paper attempts to provide a comprehensive update to the original guideline and review the methodological shortcomings identified. This review can hopefully serve as a yardstick for future studies involving this emerging clinical tool.

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Hydrogen Peroxide in Exhaled Breath Condensate in Patients with Asthma

Cited by 62 publications

References 49 publications

Disulfide Bond As a Switch for Copper-Zinc Superoxide Dismutase Activity in Asthma

Disulfide Bond As a Switch for Copper-Zinc Superoxide Dismutase Activity in Asthma

Usefulness of Noninvasive Methods for the Study of Bronchial Inflammation in the Control of Patients with Asthma

Exhaled breath condensate: a comprehensive update

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