Inhaled mannitol for the treatment of mucociliary dysfunction in patients with bronchiectasis: effect on lung function, health status and sputum.

OBJECTIVE: Inhaled mannitol increases mucus clearance in patients with bronchiectasis by an unclear mechanism. The effect of mannitol on lung function, health status and sputum properties was investigated. METHODOLOGY: Nine patients with bronchiectasis inhaled 400 mg of mannitol once daily for 12 days. Health status was assessed using the St George's Respiratory Questionnaire (SGRQ). Sputum was analysed for viscosity, elasticity, spinnability, surface tension, contact angle, solids, mucociliary transportability (MCTR) on a frog palate, and cough transportability (CTR) on a simulated cough machine. RESULTS: Lung function was unchanged with treatment (baseline FEV1 82.0 +/- 16.2%) apart from an improvement in FEF from 85.4 +/- 13% (baseline) to 90.7 +/- 14.4% (P < 0.05; 12th treatment; visit 7). The total SGRQ score (mean +/- SD) of 49.3 +/- 13.8 at baseline, decreased by 12.4 +/- 10.2 (P < 0.01; visit 7) and 10.1 +/- 9.4 units (P < 0.02) 6-10 days after treatment cessation. The baseline subscores for symptoms (72.9 +/- 11.8), activity (44.7 +/- 20.9) and impact (44.4 +/- 14.3) were reduced by 0.8 +/- 9.1 (P > 0.7), 8.4 +/- 16.0 (P > 0.1) and 19.2 +/- 13.7 (P < 0.005) units, respectively (visit 7). Mannitol reduced the baseline (mean +/- SE) surface tension from 94.5 +/- 1.4 to 84.7 +/- 2.1 mN/m (P < 0.0001), contact angle from 51.1 +/- 2.8 to 33.2 +/- 2.4 degrees (P < 0.0001), spinnability from 11.6 +/- 0.4 to 10.0 +/- 0.2 mm (P < 0.005), and solids from 5.7 +/- 0.4 to 4.3 +/- 0.7% (P < 0.02), acutely (visit 7). Viscosity, elasticity and MCTR did not change significantly, while CTR was increased from 25.8 +/- 1.0 to 34.1 +/- 2.7 mm (P < 0.003). CONCLUSION: Mannitol significantly improved the health status over 12 days and this improvement was maintained for 6-10 days after cessation of treatment. In addition, mannitol reduced the tenacity, increased the hydration of mucus acutely and improved cough clearability in patients with bronchiectasis.

Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects.

OBJECTIVE: The aim of the study was to investigate whether treatment using inhaled corticosteroids decreases airway responsiveness to inhaled mannitol in asthmatic subjects. METHODOLOGY: Before treatment or a change in treatment with inhaled corticosteroids, 18 asthmatic subjects had measurements of lung function and airway sensitivity to mannitol taken and they completed a self-administered questionnaire on asthma symptoms. The procedure was repeated 6-9 weeks after taking 800-2400 microg/day of budesonide. RESULTS: There were significant reductions in airway sensitivity (provoking dose to induce a 15% fall in FEV1 (PD15)) and airway reactivity measured by the response dose ratio (RDR; final percentage fall FEV1/total dose of mannitol administered). The PD15 (Gmean (95%CI)) increased from 78 mg (51, 117) before treatment to 289 mg (202, 414) following treatment (P < 0.001). All subjects had a significant increase beyond the repeatability of 0.9 doubling doses with seven subjects becoming unresponsive. There was a 4.2 (3.4, 4.9)-fold improvement in the RDR with the value before the treatment period 0.18 (0.12, 0.28) decreasing to 0.04 (0.03, 0.08) following treatment (P < 0.001). These improvements were associated with significant improvements in lung function and symptom severity. CONCLUSION: Treatment with the inhaled corticosteroid budesonide caused a decrease in airway sensitivity and reactivity to inhaled mannitol and this was associated with expected improvements in lung function and symptoms.