Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study

Zheng, Jinping; Kang, Jian; Huang, Shaoguang; Chen, Ping; Yao, Wan-Zen; Yang, Lan; Bai, Chunxue; Wang, Changzheng; Wang, Chen; Chen, Bao-yuan; Shi, Yi; Liu, Chun‐Tao; Li, Qiang; Wang, Zhenshan; Huang, Yijiang; Luo, Zhi-yang; Chen, Feipeng; Yuan, Jian-Zhang; Ben-tong, Yuan; Qian, Hui-Ping; Zhi, Rong-Chang; Zhong, Nanshan

doi:10.1016/s0140-6736(08)60869-7

Cited by 310 publications

(236 citation statements)

References 23 publications

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“…Antioxidant agents, such as carbocysteine, scavenge free radicals and oxidants (Zheng et al 2008). COPD patients treated with carbocysteine experienced fewer numbers of exacerbations per year (Zheng et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…COPD patients treated with carbocysteine experienced fewer numbers of exacerbations per year (Zheng et al 2008). This effect may be linked to the reduced adherence of bacterial pathogens to airway epithelial cells (Rahman and Macnee 2012) and to the downregulation of ICAM-1, a receptor for the major group of rhinovirus (Yasuda et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Carbocysteine (CARB), an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients (Zheng et al 2008). The clinical efficacy of carbocysteine seems to be more related to its antioxidant and anti-inflammatory effects than to its mucolytic activity (Rahman and Macnee 2012).…”

Section: Introductionmentioning

confidence: 99%

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Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10 −4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclearrelated factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10 −8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin Vpositive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSEmediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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“…S-CMC has been reported to reduce the number of exacerbations in COPD patients (Zheng et al, 2008). S. pneumoniae is frequently isolated from airway secretions of COPD patients during a period of exacerbation (Sethi & Murphy, 2001).…”

Section: Resultsmentioning

confidence: 99%

“…Although strain P-03-99 had the lowest level of capsule production among the tested strains, it adhered efficiently to the epithelial cells in the absence of S-CMC. However, as no correlation between capsule production and the effect of S-CMC on pneumococcal adherence was observed, it is likely that interaction of the pneumococcal capsule with the host receptor is not affected by S-CMC.S-CMC has been reported to reduce the number of exacerbations in COPD patients (Zheng et al, 2008). S. pneumoniae is frequently isolated from airway secretions of COPD patients during a period of exacerbation (Sethi & Murphy, 2001).…”

mentioning

confidence: 99%

S-Carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells

Sumitomo

Nakata

Yamaguchi

et al. 2012

Journal of Medical Microbiology

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Streptococcus pneumoniae is a major pathogen of respiratory infections that utilizes platelet-activating factor receptor (PAFR) for firm adherence to host cells. The mucolytic agent S-carboxymethylcysteine (S-CMC) has been shown to exert inhibitory effects against infection by several respiratory pathogens including S. pneumoniae in vitro and in vivo. Moreover, clinical studies have implicated the benefits of S-CMC in preventing exacerbation of chronic obstructive pulmonary disease, which is considered to be related to respiratory infections. In this study, to assess whether the potency of S-CMC is attributable to inhibition of pneumococcal adherence to host cells, an alveolar epithelial cell line stimulated with interleukin-1a was used as a model of inflamed epithelial cells. Despite upregulation of PAFR by inflammatory activation, treatment with S-CMC efficiently inhibited pneumococcal adherence to host epithelial cells. In order to gain insight into the inhibitory mechanism, the effects of S-CMC on PAFR expression were also investigated. Following treatment with S-CMC, PAFR expression was reduced at both mRNA and post-transcriptional levels. Interestingly, S-CMC was also effective in inhibiting pneumococcal adherence to cells transfected with PAFR small interfering RNAs. These results indicate S-CMC as a probable inhibitor targeting numerous epithelial receptors that interact with S. pneumoniae. INTRODUCTIONStreptococcus pneumoniae is a major cause of communityacquired pneumonia, sinusitis and otitis media, and is also associated with acute exacerbations of chronic obstructive pulmonary disease (COPD) (Miravitlles et al., 1999). Among the numerous pneumococcal adherence mechanisms responsible for causing diseases, phosphorylcholine binds specifically to platelet-activating factor receptor (PAFR) expressed on the surface of airway epithelial cells (Cundell et al., 1995(Cundell et al., , 1996Fischer, 2000). Previous in vivo experiments demonstrated that PAFR-deficient mice were less likely to develop invasive disease or had improved host defence during pneumococcal infection (Rijneveld et al., 2004). Therefore, the interaction between PAFR and phosphorylcholine plays a crucial role in the pathogenesis of pneumococcal disease.The mucolytic agent S-carboxymethylcysteine (S-CMC) is widely used as an expectorant in Europe and Asia for the treatment of respiratory diseases with phlegm production. Administration of S-CMC is also effective for COPD patients in terms of reductions in symptom exacerbation and improvements in quality of life (Zheng et al., 2008). It is generally accepted that bacterial colonization is a determinant for COPD exacerbation. Hence, it has been speculated that the potency of S-CMC against respiratory pathogens, including S. pneumoniae (Cakan et al., 2003;Suer et al., 2008), Moraxella catarrhalis (Zheng et al., 1999) and non-typable Haemophilus influenzae (Ndour et al., 2001), contributes to a reduction in episodes of respiratory infection in COPD patients. However, the mechanism by which S-C...

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Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease

Poole

Black

2010

Cochrane Database of Systematic Reviews

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Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study

Cited by 310 publications

References 23 publications

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

S-Carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease

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