Inhaled Xylitol Versus Saline in Stable Subjects With Cystic Fibrosis

Summary

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial colonization and recurrent infection of the airways. Lowering the airway surface liquid (ASL) salt concentration has been shown to increase activity of salt sensitive antimicrobial peptides. Xylitol is a 5-carbon sugar that can lower the ASL salt concentration, thus enhancing innate immunity.In this study, the investigators plan to study the safety and efficacy of 2 weeks of inhaled xylitol compared to 2 weeks of hypertonic saline in a randomized crossover design in stable subjects with cystic fibrosis

Timeline

Start

2011-05

Primary completion

2015-02

Completion

2015-02

Publications

• Background Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005 May 12;352(19):1992-2001. doi: 10.1056/NEJMra043184. No abstract available.
• Background Zabner J, Smith JJ, Karp PH, Widdicombe JH, Welsh MJ. Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro. Mol Cell. 1998 Sep;2(3):397-403. doi: 10.1016/s1097-2765(00)80284-1.
• Background Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell. 1997 Feb 21;88(4):553-60. doi: 10.1016/s0092-8674(00)81895-4.
• Background Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM. Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest. 1998 Sep 1;102(5):874-80. doi: 10.1172/JCI2410.
• Background Travis SM, Conway BA, Zabner J, Smith JJ, Anderson NN, Singh PK, Greenberg EP, Welsh MJ. Activity of abundant antimicrobials of the human airway. Am J Respir Cell Mol Biol. 1999 May;20(5):872-9. doi: 10.1165/ajrcmb.20.5.3572.
• Background Makinen KK, Bennett CA, Hujoel PP, Isokangas PJ, Isotupa KP, Pape HR Jr, Makinen PL. Xylitol chewing gums and caries rates: a 40-month cohort study. J Dent Res. 1995 Dec;74(12):1904-13. doi: 10.1177/00220345950740121501.
• Background Soderling E, Makinen KK, Chen CY, Pape HR Jr, Loesche W, Makinen PL. Effect of sorbitol, xylitol, and xylitol/sorbitol chewing gums on dental plaque. Caries Res. 1989;23(5):378-84. doi: 10.1159/000261212.
• Background Makinen KK. Long-term tolerance of healthy human subjects to high amounts of xylitol and fructose: general and biochemical findings. Int Z Vitam Ernahrungsforsch Beih. 1976;15:92-104.
• Background Uhari M, Kontiokari T, Koskela M, Niemela M. Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. BMJ. 1996 Nov 9;313(7066):1180-4. doi: 10.1136/bmj.313.7066.1180.
• Background Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN, Thorne PS, Zabner J. Safety assessment of inhaled xylitol in mice and healthy volunteers. Respir Res. 2004 Sep 16;5(1):13. doi: 10.1186/1465-9921-5-13.
• Background Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, Greenberg EP, Valore EV, Welsh MJ, Ganz T, Tack BF, McCray PB Jr. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14961-6. doi: 10.1073/pnas.95.25.14961.
• Background Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR, Look DC, Smith JJ, Welsh MJ. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11614-9. doi: 10.1073/pnas.97.21.11614.
• Background Durairaj L, Launspach J, Watt JL, Mohamad Z, Kline J, Zabner J. Safety assessment of inhaled xylitol in subjects with cystic fibrosis. J Cyst Fibros. 2007 Jan;6(1):31-4. doi: 10.1016/j.jcf.2006.05.002. Epub 2006 Jun 15.
• Background Durairaj L, Neelakantan S, Launspach J, Watt JL, Allaman MM, Kearney WR, Veng-Pedersen P, Zabner J. Bronchoscopic assessment of airway retention time of aerosolized xylitol. Respir Res. 2006 Feb 16;7(1):27. doi: 10.1186/1465-9921-7-27.
• Background Marks JH, Hare KL, Saunders RA, Homnick DN. Pulmonary function and sputum production in patients with cystic fibrosis: a pilot study comparing the PercussiveTech HF device and standard chest physiotherapy. Chest. 2004 Apr;125(4):1507-11. doi: 10.1378/chest.125.4.1507.

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