Impact of theophylline/corticosteroid combination therapy on sputum hydrogen sulfide levels in patients with COPD

Kirkham, Paul; Whiteman, Matthew; Winyard, Paul G.; Caramori, Gaetano; Gordon, Fabiana; Ford, Paul; Barnes, Peter J.; Adcock, Ian M.; Chung, Kian Fan

doi:10.1183/09031936.00131513

Cited by 18 publications

(10 citation statements)

References 9 publications

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“…However, there was no difference in H 2 S levels between subjects taking and not taking inhaled corticosteroids (data not shown). Fluticasone propionate inhalation had no effect on the levels of sputum H 2 S in patients with COPD 38. Second, bacteria in the upper and lower airways may contribute to H 2 S production, particularly that the lower airways contain bacteria with an altered bacteriome in COPD 39.…”

Section: Discussionmentioning

confidence: 95%

Sputum-to-serum hydrogen sulfide ratio in COPD

Saito

Mackay

Rossios

et al. 2014

Thorax

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Section: Discussionmentioning

confidence: 95%

Sputum-to-serum hydrogen sulfide ratio in COPD

Saito

Mackay

Rossios

et al. 2014

Thorax

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“…An alternative explanation is that AMI may restore glucocorticoid sensitivity in the cochlea through different subunits of HDAC or different pathways. Some studies reported that the combination of AMI and corticosteroid treatment could inhibit inflammatory damage by increasing H 2 S levels, a new and important regulator of inflammation 37 . Further studies, i.e.…”

Section: Discussionmentioning

confidence: 99%

Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide

Zhou

Dai

et al. 2017

Sci Rep

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Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs. We assessed hearing recovery in LPS-applied guinea pigs, which were either left untreated or were systemically treated with either dexamethasone, aminophylline, or a combination of the two. We utilized fluorescence microscopy and enzyme-linked immunosorbent assay to analyze the distribution patterns of HDAC2 and detect its levels in the cochlea. We used hematoxylin-eosin staining to examine cochlear histopathological changes. In the absence of treatment, significant hearing loss was detected in LPS-exposed animals. A synergistic effect was observed between aminophylline and dexamethasone in maintaining HDAC2 expression levels, preventing hearing loss in LPS-exposed animals and reducing cochlear damage. This study indicates that aminophylline can restore glucocorticoid sensitivity, which provides a new approach to treating patients with hearing disorders who are refractory to glucocorticoids.

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“…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). 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).…”

Section: Gyy4137: Anti-inflammatory Effectsmentioning

confidence: 99%

“…Whilst potent and selective inhibitors of CSE, CBS and 3-MST are still not available and the use of commonly used inhibitors should be viewed with caution (Asimakopoulou et al 2013;), molecular techniques have graphically illustrated the detrimental effects "H 2 S removal" has to cells, tissues and animals. Studies in animal models and human disease have revealed that endogenous H 2 S synthesis is perturbed in ageing (Qabazard et al 2014;Yang et al 2013), cardiovascular disease (Calvert et al 2009(Calvert et al , 2010Minamishima et al 2009;Yang et al 2008), pre-eclampsia , acute and chronic inflammation (Li et al 2009, diabetes (Whiteman et al 2010a) and respiratory pathologies such as asthma (Chung 2014) and chronic obstructive pulmonary disease (Chen et al 2005;Saito et al 2014;Kirkham et al 2014). These observations have consistently led to the suggestion that strategies which increase H 2 S bioavailability are viable therapeutic approaches to disease treatment.…”

Section: Introductionmentioning

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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Impact of theophylline/corticosteroid combination therapy on sputum hydrogen sulfide levels in patients with COPD

Abstract: Document type: lette

Cited by 18 publications

References 9 publications

Sputum-to-serum hydrogen sulfide ratio in COPD

Sputum-to-serum hydrogen sulfide ratio in COPD

Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

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