The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study

Abstract

It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non‐ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post‐intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post‐intervention measurement there was a significant improvement in BMC for both the mannitol (8.7±3.3%versus 2.8±0.7%) and HS (10.0±2.3%versus 3.5±0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7±2.4%) compared with its control (2.5±0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3±2.5%) and HS (5.8±1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long‐term effectiveness of mannitol. Eur Respir J 1999; 14: 678–685.

Hypertonic Saline Therapy in Cystic Fibrosis

“…Prior clinical studies also support the efficacy of various inhaled hyperosmolar agents in CF (3)(4)(5)(6). The recent study by Donaldson et al (1) concludes that hypertonic saline produces sustained elevation in airway surface liquid (ASL) volume, which improves mucociliary clearance in the airways.…”

“…Exacerbations were defined by the need for intravenous antibiotics or using a symptom score involving increased sputum production, lethargy, dyspnea, and fever. In previous smaller studies of CF subjects, a single nebulized dose of 6 -7% HS increased mucociliary clearance at 60 and 90 min, as measured by radionucleotide imaging (3,5). Increased mucociliary clearance was dose-dependent up to 12% HS in 10 adults treated with a single dose and tested at 90 min (4).…”

“…A proposed mechanism for the benefit of mannitol is based on the hypothesis that a relatively salty ASL in CF decreases innate immune defenses, such as lysozyme, lactoferrin, and ␤-defensins. If correct, a nonionic osmotic agent such as mannitol might be of benefit by reducing ASL salt concentration (5,25,42). Another proposed mechanism is the induction of cough in subjects inhaling hyperosmolar agents, which are quite irritating to the airways, although some studies conclude that changes in the mucociliary clearance are unlikely to be attributed to increased cough (3,4,22).…”

“…One mechanism involves the direct effects of NaCl and mannitol on mucus rheology (5). HS has been proposed to reduce mucin entanglement by shielding fixed negative charges on the mucin backbone; mannitol has been proposed to compete with oligopolysaccharides on mucin macromolecules, thereby disrupting hydrogen bonds and reducing entanglements (39 -41).…”

Trockenpulverinhalation bei Mukoviszidose

“…Wie dieselbe Forschergruppe feststellte, fördert Mannitol Trockenpulver bei Gesunden und bei Asthmatikern die mukoziliäre Clearance [14]. Die erste Pilotstudie bei Mukoviszidose wurde 1999 publiziert [15]. Die mit einer Gammakamera gemessene Clearance stieg nach Inhalation von 300 mg Mannitol signifikant stärker an als nach der Kontrollmedikation, und sie lag in einem ähnlichen Bereich wie nach Vernebelung von 6 %iger Kochsalzlösung.…”