Sputum hydrogen sulfide as a novel biomarker of obstructive neutrophilic asthma

Saito, Junpei; Zhang, Qingling; Hui, Chee–Kin; Macedo, Patricia; Gibeon, David; Menzies‐Gow, Andrew; Bhavsar, Pankaj; Chung, Kian Fan

doi:10.1016/j.jaci.2012.10.005

Cited by 45 publications

(38 citation statements)

References 10 publications

(7 reference statements)

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“…Current methods for distinguishing different phenotypes of asthma involve detecting sputum eosinophils (eosinophilic asthma), serum periostin levels which is a biomarker for eosinophilic asthma (Jia et al 2012) and breath nitric oxide (NO) levels (Dweik et al 2011). H 2 S is one such potential biomarker of asthma given that it was found to be elevated in the sputum of asthmatics (Chung 2014;Saito et al 2013). Endogenous serum H 2 S levels were found to be altered in chronic obstructive pulmonary disease (COPD) in man almost a decade ago (Chen et al 2005).…”

Section: Asthmamentioning

confidence: 99%

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H2S Synthesizing Enzymes: Biochemistry and Molecular Aspects

Huang

Moore

2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide (H2S) is a biologically active gas that is synthesized naturally by three enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthetase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). These enzymes are constitutively present in a wide array of biological cells and tissues and their expression can be induced by a number of disease states. It is becoming increasingly clear that H2S is an important mediator of a wide range of cell functions in health and in disease. This review therefore provides an overview of the biochemical and molecular regulation of H2S synthesizing enzymes both in physiological conditions and their modulation in disease states with particular focus on their regulation in asthma, atherosclerosis and diabetes. The importance of small molecule inhibitors in the study of molecular pathways, the current use of common H2S synthesizing enzyme inhibitors and the relevant characteristics of mice in which these enzymes have been genetically deleted will also be summarized. With a greater understanding of the molecular regulation of these enzymes in disease states, as well as the availability of novel small molecules with high specificity targeted towards H2S producing enzymes, the potential to regulate the biological functions of this intriguing gas H2S for therapeutic effect can perhaps be brought one step closer.

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Section: Asthmamentioning

confidence: 99%

“…A more recent clinical study examined levels of H 2 S in serum and sputum from 40 patients with varying degrees of severity of asthma and compared the data obtained with that of 15 healthy subjects (Saito et al 2013). H 2 S levels in sputum of asthma patients were significantly higher than those in sputum from healthy subjects.…”

Section: Asthmamentioning

confidence: 99%

H2S Synthesizing Enzymes: Biochemistry and Molecular Aspects

Huang

Moore

2015

Handbook of Experimental Pharmacology

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“…H 2 S synthesis is induced in many cell types in vitro and in vivo by pro-inflammatory mediators such as endotoxin and cytokines, and tissue and elevated blood and tissue levels of H 2 S are increased in animal models of acute and chronic inflammation, for example, haemorrhagic (Mok and Moore 2008) and septic shock (Li et al 2005;Coletta and Szabo 2013), pancreatitis Tamizhselvi et al 2007) and arthritis ). In humans, increased blood levels of H 2 S are detected in patients with endotoxic shock (Li et al 2005) and either increased (Saito et al 2013) or decreased (Wang et al 2011a) in asthma. Increased (Chen et al 2005) (or decreased (Kirkham et al 2014)) sputum H 2 S is observed in patients with chronic obstructive pulmonary disease (COPD).…”

Section: Gyy4137: Anti-inflammatory Effectsmentioning

confidence: 99%

“…Increased (Chen et al 2005) (or decreased (Kirkham et al 2014)) sputum H 2 S is observed in patients with chronic obstructive pulmonary disease (COPD). The ratio of blood/sputum H 2 S levels has been proposed as a novel biomarker for airway disease (Chung 2014;Saito et al 2013Saito et al , 2014Wang et al 2011a). Similarly, synovial fluid H 2 S levels are elevated relative to disease controls in patients with rheumatoid arthritis (Whiteman et al 2010c) and inflammatory joint disease (Whiteman and Winyard 2011).…”

Section: Gyy4137: Anti-inflammatory Effectsmentioning

confidence: 99%

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

Whiteman

Perry

Zhou³

et al. 2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide is rapidly emerging as a key physiological mediator and potential therapeutic tool in numerous areas such as acute and chronic inflammation, neurodegenerative and cardiovascular disease, diabetes, obesity and cancer. However, the vast majority of the published studies have employed crude sulfide salts such as sodium hydrosulfide (NaSH) and sodium sulfide (Na2S) as H2S "donors" to generate H2S. Although these salts are cheap, readily available and easy to use, H2S generated from them occurs as an instantaneous and pH-dependent dissociation, whereas endogenous H2S synthesis from the enzymes cystathionine γ-lyase, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase is a slow and sustained process. Furthermore, sulfide salts are frequently used at concentrations (e.g. 100 μM to 10 mM) far in excess of the levels of H2S reported in vivo (nM to low μM). For the therapeutic potential of H2S is to be properly harnessed, pharmacological agents which generate H2S in a physiological manner and deliver physiologically relevant concentrations are needed. The phosphorodithioate GYY4137 has been proposed as "slow-release" H2S donors and has shown promising efficacy in cellular and animal model diseases such as hypertension, sepsis, atherosclerosis, neonatal lung injury and cancer. However, H2S generation from GYY4137 is inefficient necessitating its use at high concentrations/doses. However, structural modification of the phosphorodithioate core has led to compounds (e.g. AP67 and AP105) with accelerated rates of H2S generation and enhanced biological activity. In this review, the therapeutic potential and limitations of GYY4137 and related phosphorodithioate derivatives are discussed.

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“…A previous study has shown that theophylline alone had no impact on serum H 2 S levels and is of limited value in the management of stable COPD [5]. Interestingly, sputum H 2 S measured in patients with asthma correlated with sputum neutrophil counts and the degree of airflow obstruction measured by forced expiratory volume in 1 s (FEV1) % predicted [6]. Moreover, combination therapy of an inhaled glucocorticoid with low-dose theophylline has been shown to attenuate airway inflammation in patients with COPD and reverse glucocorticoid resistance [7].…”

mentioning

confidence: 98%