title: Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial.
abstract: BACKGROUND
  Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF).
  
  
  OBJECTIVE
  We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted. Subjects were randomized to receive 646 mg glutathione in 4 ml (n = 73) or placebo (n = 80) via an investigational eFlow nebulizer every 12 hours for 6 months.
  
  
  RESULTS
  FEV1 (absolute values), both as pre-post differences (P = 0.180) and as area under the curves (P = 0.205), were the primary efficacy endpoints, and were not different between the glutathione group and the placebo group over the 6-month treatment period. Exploratory analysis showed an increase of FEV1 from baseline over placebo of 100 ml or 2.2% predicted; this was significant at 3 months, but not later. Subjects receiving glutathione had neither fewer pulmonary exacerbations, nor better scores for quality of life. Whereas increased glutathione and metabolites in sputum demonstrated significant delivery to the lungs, there was no indication of diminished oxidative stress to proteins or lipids, and no evidence for anti-inflammatory or antiproteolytic actions of glutathione supplemented to the airways. The adverse event incidence was similar between glutathione and placebo.
  
  
  CONCLUSIONS
  Inhaled glutathione in the dose administered did not demonstrate clinically relevant improvements in lung function, pulmonary exacerbation frequency, or patient-reported outcomes. Glutathione delivery to the airways was not associated with changes in markers of oxidation, proteolysis, or inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT00506688) and https://eudract.ema.europa.eu/index.html (EudraCT 2005-003870-88).
authors: Children's Hospital, Ludwig-Maximilians-University, Munich, Germany. matthias.griese@med.uni-muenchen.de
authors: Matthias
authors: M
authors: Griese
authors: Matthias
authors: M
authors: Kappler
authors: Claudia
authors: C
authors: Eismann
authors: Manfred
authors: M
authors: Ballmann
authors: Sibylle
authors: S
authors: Junge
authors: Ernst
authors: E
authors: Rietschel
authors: Silke
authors: S
authors: van Koningsbruggen-Rietschel
authors: Doris
authors: D
authors: Staab
authors: Claudia
authors: C
authors: Rolinck-Werninghaus
authors: Uwe
authors: U
authors: Mellies
authors: Thomas
authors: T
authors: Köhnlein
authors: Thomas
authors: T
authors: Wagner
authors: Susanne
authors: S
authors: König
authors: Helmut
authors: H
authors: Teschler
authors: Hans-Eberhard
authors: HE
authors: Heuer
authors: Matthias
authors: M
authors: Kopp
authors: Susanne
authors: S
authors: Heyder
authors: Jutta
authors: J
authors: Hammermann
authors: Peter
authors: P
authors: Küster
authors: Marguerite
authors: M
authors: Honer
authors: Ulrich
authors: U
authors: Mansmann
authors: Ingrid
authors: I
authors: Beck-Speier
authors: Dominik
authors: D
authors: Hartl
authors: Carola
authors: C
authors: Fuchs
authors: Andreas
authors: A
authors: Hector
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005978:Glutathione / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D005978:Glutathione