Chest
Volume 137, Issue 4, April 2010, Pages 861-868
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Original Research
Cystic Fibrosis
Inhaled Mannitol Improves the Hydration and Surface Properties of Sputum in Patients With Cystic Fibrosis

https://doi.org/10.1378/chest.09-2017Get rights and content

Background

The airway mucus in patients with cystic fibrosis (CF) is dehydrated and adhesive and accumulates in the airways, resulting in chronic inflammation, infection, and progressive loss of lung function. Inhaled mannitol improves mucus clearance and, when administered over 2 weeks, it improves lung function in CF (Jaques et al. Chest. 2008;133(6):1388-1396). The changes in the physical properties of sputum after a 2-week treatment with mannitol were investigated in the same subjects with CF.

Methods

Sputum was collected before and at the end of the 2-week treatment period from 28 subjects with CF who participated in the double-blind crossover study. Mannitol or placebo 420 mg bid was inhaled over 2 weeks. The solids content, surface tension, contact angle, and viscoelasticity were measured.

Results

Two-week treatment with mannitol reduced the solids from 7.3% ± 3.0% to 5.7% ± 3.0% (P = .012), surface tension from 83.1 ± 7.2 to 78.6 ± 8.0 mN/m (P < .039), and contact angle from 52.4 ± 7.7 to 47.9 ± 7.3 degrees. There was no significant change in the viscoelastic properties of sputum (P > .1). Placebo treatment had no significant effect on the sputum properties. The change in solids content correlated with the change in both FEV1 (r = −0.78, P = .004) and forced expiratory flow in the middle half of the FVC (r = −0.80, P = .003), and the percentage change in surface tension and contact angle correlated with the percentage change in the FEV1 (r = −0.73, P = .012 and r = −0.63, P = .03, respectively) in these subjects.

Conclusion

Treatment with inhaled mannitol over 2 weeks improved the hydration and surface properties of sputum in patients with CF. This effect was sustained and correlated with airway function changes.

Trial registration

clinicaltrials.gov; Identifier: NCT00455130

Section snippets

Subjects

Thirty-nine subjects with CF, clinically stable, from Australia and New Zealand were randomized, and 35 subjects completed both treatments of the study.7 Subjects were > 8 years old and had FEV1 between 41% and 91% predicted. Eligible subjects were premedicated with 400 μg of salbutamol prior to having an airway challenge with mannitol (Aridol; Pharmaxis Ltd; Frenchs Forest, NSW, Australia) following a standard protocol8 to exclude subjects with airway hyperresponsiveness to mannitol. Subjects

Results

There was no significant difference in the sputum properties between mannitol and placebo treatment at baseline and after a 2-week washout period. In addition, the order of treatment did not influence any of the sputum properties (ie, there was no carryover effect).

The solids content and surface properties of sputum were significantly reduced after a 2-week treatment with mannitol inhaled bid in patients with CF. This reduction was observed approximately 12 h after the last dose. The reduction

Discussion

Treatment with inhaled mannitol over 2 weeks improved the hydration and surface properties of sputum in patients with CF. The effect of mannitol on the sputum properties was evident for approximately 12 h after the end of the last treatment dose. This is the first in vivo study to show a sustained effect of mannitol on the sputum properties in CF. In addition, the reduction in solids content and surface properties correlated with the improvement in the lung function in these patients after 2

Acknowledgments

Author contributions: Dr Daviskas: contributed to the study design, measurement and analysis of sputum properties, interpretation of the findings, and writing the manuscript.

Dr Anderson: contributed to the study design, interpretation of the findings, and writing the manuscript.

Ms Jaques: contributed to the study design, interpretation of the findings, and writing the manuscript.

Dr Charlton: contributed to the study design, interpretation of the findings, and writing the manuscript.

References (0)

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Funding/Support: This study was sponsored by Pharmaxis Ltd.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).

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