title: Airway-rehydrating agents for the treatment of cystic fibrosis: past, present, and future.
abstract: OBJECTIVE
  To review and evaluate airway-rehydrating agents used for the treatment of cystic fibrosis (CF).
  
  
  METHODS
  Literature was retrieved through MEDLINE (1977-August 2010), Cochrane Library, and International Pharmaceutical Abstracts (1977-August 2010). Search terms used included hypertonic saline, inhaled mannitol, denufosol, Moli1901, lancovutide, and cystic fibrosis. Reference citations from selected articles were reviewed.
  
  
  METHODS
  All articles published in English identified from the data sources were evaluated for inclusion. Clinical trials in humans and relevant review articles were evaluated for each airway-rehydrating agent.
  
  
  RESULTS
  Use of airway-rehydrating agents for the treatment of CF is an expanding area. Hypertonic saline (7% NaCl) is currently the only commercially available airway-rehydrating agent recommended for chronic therapy in patients with CF and is being evaluated in younger patients. Inhaled mannitol is an investigational dry-powder inhalation agent that improves mucus clearance in a similar manner to hypertonic saline and produced a statistically significant increase in forced expiratory volume in 1 second in a Phase 3 trial. Denufosol, a P2Y(2) agonist, rehydrates the airway surface liquid bypassing the basic CF transmembrane conductance regulator (CFTR) protein defect. It produces improvement in pulmonary function and is being further evaluated in a Phase 3 trial. Lancovutide (Moli1901) is an investigational agent in early-phase trials that activates a calcium-dependent chloride channel, allowing chloride to enter the airway.
  
  
  CONCLUSIONS
  Hypertonic saline is the primary airway-rehydrating agent used in the treatment of CF. Inhaled mannitol may become an alternative to hypertonic saline since it is faster and easier to administer. It remains unclear whether denufosol and lancovutide will be synergistic or antagonistic with hypertonic saline. Both agents have a unique mechanism of action that bypasses the basic CFTR defect.
authors.affiliation: Department of Pharmacy Services and College of Pharmacy, University of Michigan Hospitals and Health Centers, Ann Arbor, MI, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Pettit
authors.forename: Cary E
authors.initials: CE
authors.lastname: Johnson
mesh_terms: D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015532:Rehydration Solutions / Q000494:pharmacology / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000187:drug effects / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology; D019141:Respiratory System Agents / Q000627:therapeutic use*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015532:Rehydration Solutions; D019141:Respiratory System Agents; D012462:Saline Solution, Hypertonic