Durability of Hypertonic Saline for Enhancing Mucociliary Clearance in Cystic Fibrosis

Summary

Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.

Timeline

Start

2009-11

Primary completion

2010-05

Completion

2010-05

Publications

• Background Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006 Jan 19;354(3):241-50. doi: 10.1056/NEJMoa043891.
• Background Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
• Background Bennett WD, Olivier KN, Zeman KL, Hohneker KW, Boucher RC, Knowles MR. Effect of uridine 5'-triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis. Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1796-801. doi: 10.1164/ajrccm.153.6.8665037.
• Background Donaldson SH, Boucher RC. Sodium channels and cystic fibrosis. Chest. 2007 Nov;132(5):1631-6. doi: 10.1378/chest.07-0288.
• Background Pons G, Marchand MC, d'Athis P, Sauvage E, Foucard C, Chaumet-Riffaud P, Sautegeau A, Navarro J, Lenoir G. French multicenter randomized double-blind placebo-controlled trial on nebulized amiloride in cystic fibrosis patients. The Amiloride-AFLM Collaborative Study Group. Pediatr Pulmonol. 2000 Jul;30(1):25-31. doi: 10.1002/1099-0496(200007)30:13.0.co;2-c.
• Background Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.
• Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.

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