Objective

To review and evaluate airway-rehydrating agents used for the treatment of cystic fibrosis (CF).

Data Sources:

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, Moli 1901, lancovutide, and cystic fibrosis. Reference citations from selected articles were reviewed.

Study Selection And Data Extraction:

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,

Data Synthesis:

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 P2Y₂ 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 (Moli 1901) is an investigation at 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.

Search results

Airway-Rehydrating Agents for the Treatment of Cystic Fibrosis: Past,Present,and Future

Dabigatran