Written by Tatjana Djakovic, Staff Writer. Those inhaling mannitol had 29% less worsening episodes and 30% less need for antibiotics.
Lung health is severely impaired in cystic fibrosis patients, because of a defective chloride channel that results in an accumulation of thick, sticky mucus that makes breathing difficult and impairs quality of life (1). The genetic mutation that occurs in cystic fibrosis patients wreaks havoc on many body organs including the pancreas and the digestive and immune systems; however most of the mortality occurs due to the deterioration of lung function (2). As the disease progresses, there is a change in the airways due to chronic bacterial infections, production of abnormally sticky fluid, defective clearance of airway secretions, and inflammation (3). Additionally, there are episodes of severe worsening of signs and symptoms which are clinically important events that have been shown to cause irreversible lung function (4).
Mannitol is a naturally occurring sugar alcohol which is safe for human consumption, and has been analyzed in previous studies to improve hydration of airways and increase mucus clearance in patients with respiratory illnesses (5). In this recent study, mannitol was tested in cystic fibrosis patients in order to improve lung function, decrease worsening episodes and potentially improve quality and length of life.
The data was gathered from two double-blind, randomized, controlled, paralleled group phase III studies in which 600 patients inhaled either mannitol (400mg) or control (mannitol 50 mg- determined to be non-therapeutic) twice a day for 26 weeks. The patients were categorized by age into three groups: children (6 to 11 years), adolescents (12 to 17 years) and adults (>18 years) and were permitted to continue all therapies except for saline solution that works similarly to mannitol (6).
The change in lung function was analyzed using forced expiratory volume, which is a measure of the maximum amount of air a person can forcefully exhale in one second. It is then converted to percentage of normal amount of air exhaled predicted by an individual’s age and gender (7). For instance, 80% of the predicted amount is classified as normal lung function and anything below that is indicated as obstruction. The patients in the mannitol and the control group before the study began had approximately 59% of predicted value which indicated moderate obstruction (6).
There were significant improvements overall in the mannitol group compared to the control as seen in the 3.56% improvement in the forced expiratory volume (p<0.001) and increase of 73.4 ml in the volume of air that is exhaled (p<0.001). Younger patients aged 6-11 showed the largest changes from baseline (3.14% improvement, p=0.03), adults showed a 2.55% improvement, (p=0.002), while the adolescents did not show a significant improvement, which the authors suggest might be due to management of cystic fibrosis being particularly challenging in adolescents. These improvements were observed by the first evaluation at 6 weeks, and maintained over 26 weeks. Additionally, the incidence of patients with worsening episodes and need for antibiotics was reduced by 29% (p=0.033) and 30% (p=0.033) respectively in the mannitol group during the study (6).
There is some concern over mannitol acting as nutrition for the bacteria colonizing in the lungs, and fortunately this study showed that this is not the case, as there were no significant differences in the bacterial growth in either of the groups (8). The findings of this study are clinically important, because mannitol is a safe, well tolerated and easily administered substance that shows significant improvement in lung function in cystic fibrosis patients.
Source: Bilton, Diana, Gabriel Bellon, Brett Charlton, Peter Cooper, Kris De Boeck, Patrick A. Flume, Howard G. Fox et al. “Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis.” Journal of Cystic Fibrosis 12, no. 4 (2013): 367-376.
© 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Posted September 30, 2013.
References:
- Lyczak, Jeffrey B., Carolyn L. Cannon, and Gerald B. Pier. “Lung infections associated with cystic fibrosis.” Clinical Microbiology Reviews 15.2 (2002): 194-222.
- Wiehe, M., and K. Arndt. “Cystic fibrosis: a systems review.” AANA journal 78.3 (2010): 246.
- Henke MO, Ratjen F. Mucolytics in cystic fibrosis. Paediatr Respir Rev 2007;8:24-9.
- Sanders DB, et al. “Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010;182:627-32.
- Allison RG. Dietary sugars in health and disease. IV. Mannitol. NTIS PB Report (PB-221 211); 1979. p.94.
- Bilton, Diana, et al. “Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis.” Journal of Cystic Fibrosis (2012).
- Knudson, Ronald J., et al. “The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age.” The American review of respiratory disease 113.5 (1976): 587-600.
- Pettit RS, Johnson CE. Airway-rehydrating agents for the treatment of cystic fibrosis: past, present, and future. Ann Pharmacother 2011;45(1);49-59.
