Excessive active absorption of sodium is a unique abnormality of the airway epithelium in patients with cystic fibrosis. This defect is associated with thickened mucus and poor clearance of airway secretions and may contribute to the pulmonary disease in these patients. To study whether the inhibition of excessive absorption of sodium might affect the course of lung disease in cystic fibrosis, we performed a double-blind, crossover trial comparing aerosolized amiloride (5 mmol per liter; 3.5 ml four times daily), a sodium-channel blocker, with vehicle alone. Fourteen of the 18 adult patients initially enrolled in the study completed the one-year trial (25 weeks for each treatment). The mean (+/- SEM) loss of forced vital capacity (FVC) was reduced from 3.39 +/- 1.13 ml per day during treatment with vehicle alone to 1.44 +/- 0.67 ml per day during treatment with amiloride (P less than 0.04). A measured index of sputum viscosity and elasticity was abnormal during treatment with vehicle alone and improved during treatment with amiloride. Calculated indexes of mucociliary and cough clearance also improved during amiloride treatment. No systemic, respiratory, or subjective toxic effects of amiloride were noted. We conclude from this preliminary study that aerosolized amiloride can be safely administered to adults with cystic fibrosis. The slowing of the loss of FVC and the improvement in sputum viscosity and elasticity suggest a beneficial clinical effect. Aerosolized amiloride deserves further evaluation in the treatment of lung disease in patients with cystic fibrosis.
Source Information
Division of Pulmonary Diseases, University of North Carolina, Chapel Hill 27599-7020.
This article has been cited by other articles:
Hasani, A, Chapman, T., McCool, D, Smith, R., Dilworth, J., Agnew, J.
(2008). Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chronic Respiratory Disease
5: 81-86
[Abstract]
Hirsh, A. J., Zhang, J., Zamurs, A., Fleegle, J., Thelin, W. R., Caldwell, R. A., Sabater, J. R., Abraham, W. M., Donowitz, M., Cha, B., Johnson, K. B., St. George, J. A., Johnson, M. R., Boucher, R. C.
(2008). Pharmacological Properties of N-(3,5-Diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine Methanesulfonate (552-02), a Novel Epithelial Sodium Channel Blocker with Potential Clinical Efficacy for Cystic Fibrosis Lung Disease. J. Pharmacol. Exp. Ther.
325: 77-88
[Abstract][Full Text]
Carattino, M. D., Passero, C. J., Steren, C. A., Maarouf, A. B., Pilewski, J. M., Myerburg, M. M., Hughey, R. P., Kleyman, T. R.
(2008). Defining an inhibitory domain in the {alpha}-subunit of the epithelial sodium channel. Am. J. Physiol. Renal Physiol.
294: F47-F52
[Abstract][Full Text]
Donaldson, S. H., Boucher, R. C.
(2007). Sodium Channels and Cystic Fibrosis. Chest
132: 1631-1636
[Abstract][Full Text]
Middleton, P. G., Kidd, T. J., Williams, B.
(2005). Combination aerosol therapy to treat Burkholderia cepacia complex. Eur Respir J
26: 305-308
[Abstract][Full Text]
Hirsh, A. J., Sabater, J. R., Zamurs, A., Smith, R. T., Paradiso, A. M., Hopkins, S., Abraham, W. M., Boucher, R. C.
(2004). Evaluation of Second Generation Amiloride Analogs as Therapy for Cystic Fibrosis Lung Disease. J. Pharmacol. Exp. Ther.
311: 929-938
[Abstract][Full Text]
Noone, P G, Southern, K W
(2004). Unravelling salt transport in cystic fibrosis. Thorax
59: 916-917
[Full Text]
Srivastava, M., Eidelman, O., Zhang, J., Paweletz, C., Caohuy, H., Yang, Q., Jacobson, K. A., Heldman, E., Huang, W., Jozwik, C., Pollard, B. S., Pollard, H. B.
(2004). Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc. Natl. Acad. Sci. USA
101: 7693-7698
[Abstract][Full Text]
Boucher, R.C.
(2004). New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J
23: 146-158
[Abstract][Full Text]
Gibson, R. L., Burns, J. L., Ramsey, B. W.
(2003). Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. Am. J. Respir. Crit. Care Med.
168: 918-951
[Abstract][Full Text]
Ballard, S. T., Trout, L., Mehta, A., Inglis, S. K.
(2002). Liquid secretion inhibitors reduce mucociliary transport in glandular airways. Am. J. Physiol. Lung Cell. Mol. Physiol.
283: L329-L335
[Abstract][Full Text]
Lyczak, J. B., Cannon, C. L., Pier, G. B.
(2002). Lung Infections Associated with Cystic Fibrosis. Clin. Microbiol. Rev.
15: 194-222
[Abstract][Full Text]
Vallet, V., Pfister, C., Loffing, J., Rossier, B. C.
(2002). Cell-Surface Expression of the Channel Activating Protease xCAP-1 Is Required for Activation of ENaC in the Xenopus Oocyte. J. Am. Soc. Nephrol.
13: 588-594
[Abstract][Full Text]
App, E.M., Baran, D., Dab, I., Malfroot, A., Coffiner, M., Vanderbist, F., King, M.
(2002). Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis. Eur Respir J
19: 294-302
[Abstract][Full Text]
Bridges, R. J., Newton, B. B., Pilewski, J. M., Devor, D. C., Poll, C. T., Hall, R. L.
(2001). Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437. Am. J. Physiol. Lung Cell. Mol. Physiol.
281: L16-L23
[Abstract][Full Text]
Rodgers, H.C., Knox, A.J.
(2001). Pharmacological treatment of the biochemical defect in cystic fibrosis airways. Eur Respir J
17: 1314-1321
[Abstract][Full Text]
GEDDES, D M, ALTON, E W F W
(1999). The CF gene: 10 years on. Thorax
54: 1052-1054
[Full Text]
NOONE, P. G., BENNETT, W. D., REGNIS, J. A., ZEMAN, K. L., CARSON, J. L., KING, M., BOUCHER, R. C., KNOWLES, M. R.
(1999). Effect of Aerosolized Uridine-5'-Triphosphate on Airway Clearance with Cough in Patients with Primary Ciliary Dyskinesia. Am. J. Respir. Crit. Care Med.
160: 144-149
[Abstract][Full Text]
HOFMANN, T., STUTTS, M. J., ZIERSCH, A., RUCKES, C., WEBER, W. M., KNOWLES, M. R., LINDEMANN, H., BOUCHER, R. C.
(1998). Effects of Topically Delivered Benzamil and Amiloride on Nasal Potential Difference in Cystic Fibrosis. Am. J. Respir. Crit. Care Med.
157: 1844-1849
[Abstract][Full Text]
Stern, R. C.
(1997). The Diagnosis of Cystic Fibrosis. NEJM
336: 487-491
[Full Text]
Ramsey, B. W.
(1996). Management of Pulmonary Disease in Patients with Cystic Fibrosis. NEJM
335: 179-188
[Full Text]
Tran, J. H., Brennan, K. M.
(1996). Management of the Child With Cystic Fibrosis. Journal of Pharmacy Practice
9: 75-90
[Abstract]
Egan, T. M., Detterbeck, F. C., Mill, M. R., Paradowski, L. J., Lackner, R. P., Ogden, W. D., Yankaskas, J. R., Westerman, J. H., Thompson, J. T., Weiner, M. A., Cairns, E. L., Wilcox, B. R.
(1995). Improved results of lung transplantation for patients with cystic fibrosis. J. Thorac. Cardiovasc. Surg.
109: 224-235
[Abstract][Full Text]
Fuchs, H. J., Borowitz, D. S., Christiansen, D. H., Morris, E. M., Nash, M. L., Ramsey, B. W., Rosenstein, B. J., Smith, A. L., Wohl, M. E., The Pulmozyme Study Group,
(1994). Effect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis. NEJM
331: 637-642
[Abstract][Full Text]
Davis, P. B.
(1994). Evolution of Therapy for Cystic Fibrosis. NEJM
331: 672-673
[Full Text]
Weinberger, S. E.
(1993). Recent Advances in Pulmonary Medicine- First of Two Parts. NEJM
328: 1389-1397
[Full Text]
Collins, F.
(1992). Cystic fibrosis: molecular biology and therapeutic implications. Science
256: 774-779
[Abstract]
Previous
