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Inhaled Mannitol Improves Lung Function in Cystic Fibrosis^*

^* From the Department of Clinical Research (Ms. Jaques and Dr. Charlton), Pharmaxis Ltd, Frenchs Forest, NSW, Australia; the Department of Respiratory and Sleep Medicine (Drs. Daviskas, Bye, and Anderson), Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Coast City Country Training Pty, Ltd (Dr. Turton) Canberra, ACT, Australia; the Department of Respiratory Medicine (Drs. McKay and Cooper), Children’s Hospital at Westmead, Sydney, NSW, Australia; the Department of Allergy, Immunology, and Respiratory Medicine (Dr. Stirling), The Alfred Hospital, Melbourne, VIC, Australia; the Department of Respiratory Medicine (Dr. Robertson), Royal Children’s Hospital, Melbourne, VIC, Australia; the Department of Paediatrics and Child Health (Dr. LeSouëf), University of Western Australia, Perth, WA, Australia; and the Department of Epidemiology (Dr. Shadbolt), The Canberra Hospital, Canberra, ACT, Australia.

Correspondence to: Anna Jaques, BSc, MPH, Pharmaxis Ltd, 2/10 Rodborough Rd, Frenchs Forest, NSW, 2086 Australia; e-mail: anna.jaques{at}pharmaxis.com.au

Abstract

Background: The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period.

Methods: This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to-moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2 weeks. Following a 2-week washout period, subjects were entered in the reciprocal treatment arm. Lung function, respiratory symptoms, quality of life, and safety were assessed.

Results: Mannitol treatment increased FEV₁ from baseline by a mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3% (95% CI, – 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with placebo (0 mL; 95% CI, – 64.7 to 64.7). The forced expiratory flow in the middle half of the FVC increased by 15.5% (95% CI, – 6.5 to 24.6) compared to that with placebo (increase, 0.7%; 95% CI, – 8.3 to 9.7; p < 0.02). The safety profile of mannitol was adequate, and no serious adverse events related to treatment were observed.

Conclusions: Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated.

Trial registration: Clinical Trials.gov Identifier: NCT00455130 [ClinicalTrials.gov]

Key Words: cystic fibrosis • mannitol • mucoactive • mucus clearance • randomized clinical trial