title: Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.
abstract: BACKGROUND
  Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis.
  
  
  METHODS
  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: November 2008.
  
  
  METHODS
  Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis.
  
  
  METHODS
  The authors independently assessed trials for inclusion, analysed methodological quality and extracted data.
  
  
  RESULTS
  Searches identified 18 trials; eight (seven older than 10 years) (234 participants) are included. Three trials of nebulized thiol derivatives were identified (one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Five studies of oral thiol derivatives were identified. Three studies compared n-acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo; and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.
  
  
  CONCLUSIONS
  We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.
authors.affiliation: Department of Respiratory Medicine, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK, B9 5SS. edward.nash@heartofengland.nhs.uk
authors.forename: Edward F
authors.initials: EF
authors.lastname: Nash
authors.forename: Anne
authors.initials: A
authors.lastname: Stephenson
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000551:Ambroxol / Q000008:administration & dosage*; D002233:Carbocysteine / Q000008:administration & dosage*; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D005100:Expectorants / Q000008:administration & dosage*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy; D009079:Mucociliary Clearance / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic
chemical_list: D005100:Expectorants; D000551:Ambroxol; D002233:Carbocysteine; D000111:Acetylcysteine