Inhaled mannitol improves lung function in cystic fibrosis.
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 FEV(1) 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.


BACKGROUND
(ClinicalTrials.gov) Identifier: NCT00455130.
Jaques
Anna
A
Department of Clinical Research, Pharmaxis Ltd, Frenchs Forest, NSW, Australia. Electronic address: anna.jaques@pharmaxis.com.au.
Daviskas
Evangelia
E
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Turton
James A
JA
Coast City Country Training Pty, Ltd, Canberra, ACT, Australia.
McKay
Karen
K
Department of Respiratory Medicine, Children's Hospital at Westmead, Sydney, NSW, Australia.
Cooper
Peter
P
Department of Respiratory Medicine, Children's Hospital at Westmead, Sydney, NSW, Australia.
Stirling
Robert G
RG
Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia.
Robertson
Colin F
CF
Department of Respiratory Medicine, Royal Children's Hospital, Melbourne, VIC, Australia.
Bye
Peter T P
PTP
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
LeSouëf
Peter N
PN
Department of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
Shadbolt
Bruce
B
Department of Epidemiology, The Canberra Hospital, Canberra, ACT, Australia.
Anderson
Sandra D
SD
Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Charlton
Brett
B
Department of Clinical Research, Pharmaxis Ltd, Frenchs Forest, NSW, Australia.
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D002648:Child; D016001:Confidence Intervals; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004234:Diuretics, Osmotic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D004234:Diuretics, Osmotic; D008353:Mannitol