Inhaled hyperosmolar agents for bronchiectasis

Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients. Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation.

To determine whether inhaled hyperosmolar substances are efficacious in the treatment of bronchiectasis

MEDLINE and Cochrane databases were searched, and leaders in the field contacted.

Any trial using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis.

One reference were identified by the searches conducted.

Only one trial was identified, a crossover study of 11 patients with bronchiectasis. The outcome measure was tracheobronchial clearance of a particulate radioaerosol after inhalation of dry mannitol on a single occasion, with appropriate controls. Airway clearance doubled in the central and intermediate regions of the lung, but not in the peripheral region, after mannitol administration. No side effects were observed, but two patients were premedicated with nedocromil to prevent bronchospasm. A further search conducted in September 2001 did not identify any further studies.

Dry powder mannitol has been shown to improve tracheobronchial clearance in bronchiectasis, as well as cystic fibrosis, asthmatics, and normal subjects. It is not yet available for clinical use. Hypertonic saline has not been specifically tested in bronchiectasis, but improve clearance in these other conditions and in chronic bronchitis. Longer term randomised controlled studies of mannitol and hypertonic saline with clinical endpoints are now needed.