title: Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients.
abstract: BACKGROUND
  Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD). However, the required dose and responder phenotype remain unclear. The current study investigated the effect of high-dose NAC on airway geometry, inflammation, and oxidative stress in COPD patients. Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy.
  
  
  METHODS
  Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months.
  
  
  RESULTS
  Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC (P = 0.011) and glutathione peroxidase at baseline (P = 0.036). Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC (P = 0.02), changes in glutathione peroxidase levels (P = 0.035), and reduction in lobar functional residual capacity levels (P = 0.00084). In the limited set of responders to NAC therapy, the changes in airway resistance were in the same order as changes induced by budesonide/formoterol.
  
  
  CONCLUSIONS
  A combination of glutathione, glutathione peroxidase, and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy. The findings of this small pilot study need to be confirmed in a larger pivotal trial.
authors.affiliation: FluidDA nv, Kontich, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: De Backer
authors.forename: Wim
authors.initials: W
authors.lastname: Vos
authors.forename: Cedric
authors.initials: C
authors.lastname: Van Holsbeke
authors.forename: Samir
authors.initials: S
authors.lastname: Vinchurkar
authors.forename: Rita
authors.initials: R
authors.lastname: Claes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Parizel
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Backer
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects*; D000975:Antioxidants / Q000627:therapeutic use*; D003198:Computer Simulation; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume; D005652:Functional Residual Capacity; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D061330:Multidetector Computed Tomography; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D005979:Glutathione Peroxidase; D005978:Glutathione; D000111:Acetylcysteine
keywords: N-acetylcysteine; chronic obstructive pulmonary disease; computational fluid dynamics; computed tomography; functional respiratory imaging