Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis

Calabrese, Cecilia; Tosco, Antonella; Abete, Pasquale; Carnovale, Vincenzo; Basile, Christian; Magliocca, A.; Quattrucci, Serena; Sanctis, Stefania De; Alatri, F.; Mazzarella, Gennaro; Pietro, L. De; Turiño, Carlos del Risco; Melillo, Enrico; Buonpensiero, Paolo; Pasqua, A. Di; Raia, Valeria

doi:10.1016/j.jcf.2014.09.014

Cited by 25 publications

(21 citation statements)

References 26 publications

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“…Since the early reports of impaired glutathione efflux in CF, inhaled GSH has been the focus of a number of treatment trials, which demonstrated either unsatisfactory or conflicting data with regard to improvement of lung function and decrease of oxidative stress [34][35][36][37][38][39].…”

Section: Relationship Between Glutathione Species and Markers Of Neutmentioning

confidence: 99%

“…Inhibition of MPO would block oxidant production at the source and might help restore glutathione levels at the same time as decreasing oxidative stress. Also, long term treatment with inhaled glutathione may be beneficial, an avenue only one study has explored to date [35]. Furthermore, all studies on inhaled glutathione were done on patients older than six years.…”

Section: Relationship Between Glutathione Species and Markers Of Neutmentioning

confidence: 99%

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Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency

Dickerhof

Pearson

Hoskin

et al. 2017

Free Radical Biology and Medicine

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Neutrophil-derived myeloperoxidase (MPO) is recognized as a major source of oxidative stress at the airway surface of a cystic fibrosis (CF) lung where, despite limited evidence, the antioxidant glutathione is widely considered to be low. The aims of this study were to establish whether oxidative stress or glutathione status are associated with bronchiectasis and whether glutathione deficiency is inherently linked to CF or a consequence of oxidative stress. MPO was measured by ELISA in 577 bronchoalveolar lavage samples from 205 clinically-phenotyped infants and children with CF and 58 children without CF (ages 0.2-6.92 years). Reduced glutathione (GSH), oxidized glutathione species (GSSG; glutathione attached to proteins, GSSP; glutathione sulfonamide, GSA) and allantoin, an oxidation product of uric acid, were measured by mass spectrometry. The odds of having bronchiectasis were associated with MPO and GSSP. GSH was low in children with CF irrespective of oxidation. Oxidized glutathione species were significantly elevated in CF children with pulmonary infections compared to uninfected CF children. In non-CF children, infections had no effect on glutathione levels. An inadequate antioxidant response to neutrophil-mediated oxidative stress during infections exists in CF due to an inherent glutathione deficiency. Effective delivery of glutathione and inhibition of MPO may slow the development of bronchiectasis.

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Section: Relationship Between Glutathione Species and Markers Of Neutmentioning

confidence: 99%

Section: Relationship Between Glutathione Species and Markers Of Neutmentioning

confidence: 99%

Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency

Dickerhof

Pearson

Hoskin

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…Glutathione has been shown to enhance the functional activity of different immune cells against oxidative stress‐induced lung damage and is depleted in CF. Treatment with inhaled glutathione for 12 months in patients >6 years of age with FEV1 >40% predicted demonstrated no change in FEV1% predicted in patients 6–18 years of age, but improvement in those >18 years of age and in those with an FEV1 <81% predicted …”

Section: Therapiesmentioning

confidence: 96%

Pediatric Pulmonologyyear in review 2015: Part 4

Savant

McColley

2016

Pediatr Pulmonol.

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“…However, in CF patients, GSH levels in whole blood, blood neutrophils lymphocytes and epithelial lung fluid are markedly decreased [89]. Replenishment of GSH levels in CF has thus been investigated in a number of human studies using either inhaled GSH [90,91] or oral N-acetylcysteine, a GSH precursor [92]. These studies demonstrated the feasibility of successfully delivering GSH to human lung, with a significant improvement in lung function (FEV1), especially in patients with moderate lung disease.…”

Section: New Non-antibiotic Treatmentsmentioning

confidence: 99%

Pseudomonas aeruginosa Extracellular Secreted Molecules Have a Dominant Role in Biofilm Development and Bacterial Virulence in Cystic Fibrosis Lung Infections

Das¹,

Manos²

2017

Progress in Understanding Cystic Fibrosis

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Cystic fibrosis (CF) is a genetic disorder that predominantly affects Caucasian populations. Pseudomonas aeruginosa is the most important Gram-negative pathogen that persists in CF patients' lungs. By evading host defence mechanisms and persisting, it is ultimately responsible for the morbidity and mortality of about 80% of CF patients worldwide. P. aeruginosa is also responsible for infections in burns, wounds, eyes, nosocomial patients and HIV patients. Prevalence and progression of infection by P. aeruginosa in the host is dependent on secretion of numerous extracellular molecules such as polysaccharides, proteases, eDNA, pyocyanin and pyoverdine. These molecules have multiple roles in facilitating P. aeruginosa colonisation and virulence. Pyocyanin is one of the major factors dictating progression of infection and biofilm formation. Pyocyanin is a potent virulence factor causing host cell death in CF patients. In this chapter, we have outlined the roles of various extracellular molecules secreted by P. aeruginosa and specifically focused on the role of pyocyanin in inducing eDNA production, binding to eDNA via intercalation and facilitating biofilm promoting factors, whilst inducing oxidative stress to host cells via production of reactive oxygen species. In line with this, we have described the current challenges in treatment of CF infections and the development of new strategies to control P. aeruginosa infections.

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Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis

Abstract: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.

Cited by 25 publications

References 26 publications

Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency

Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency

Pediatric Pulmonologyyear in review 2015: Part 4

Pseudomonas aeruginosa Extracellular Secreted Molecules Have a Dominant Role in Biofilm Development and Bacterial Virulence in Cystic Fibrosis Lung Infections

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