|
 |
|
|||||||
|
|||||||||
© 2007 The American Thoracic Society
doi: 10.1513/pats.200703-042BR
Mucociliary Clearance as an Outcome Measure for Cystic Fibrosis Clinical Research
1 Department of Medicine, University of North Carolina, Chapel Hill, North Carolina; 2 Departments of Medicine and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania; 3 Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland; and 4 Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Correspondence and requests for reprints should be addressed to Scott H. Donaldson, M.D., Cystic Fibrosis Research and Treatment Center, 6007B Thurston Bowles Building, CB#7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail: scott_donaldson{at}med.unc.edu
ABSTRACT
Current concepts of cystic fibrosis (CF) pathophysiology link ion transport abnormalities to reduced airway surface liquid (ASL) hydration and impaired mucus clearance. It is likely that correction of the defects that cause ASL dehydration will prevent degradation of mucus clearance, thereby preventing the initiation and/or progression of CF lung disease. A number of novel therapeutic agents aimed at the earliest steps in disease pathogenesis are now under development for the treatment of CF lung disease. Consequently, there is a tremendous need to develop methods that directly assess the effects of these agents on the underlying pathophysiologic process in the target organ. The measurement of mucociliary clearance (MCC) is a highly biologically relevant outcome, but one that is in need of further development. Here, we describe important methodologic aspects of MCC measurement and issues that have limited its use as an outcome measure in the past. Furthermore, we outline the steps that are being carried out now, and will be carried out in the future, to improve the performance of these studies in clinical trials. A systematic approach to optimizing and standardizing the measurement of MCC should greatly advance our ability to assess novel therapies at a relatively early stage of drug development. The resulting data may then be used to select those candidates that should be rapidly advanced into larger clinical trials.
Key Words: cystic fibrosis • mucociliary clearance • mucus clearance • scintigraphy
Related articles in Proceedings of the American Thoracic Society:
- Advancing Outcome Measures for the New Era of Drug Development in Cystic Fibrosis
- Nicole Mayer-Hamblett, Bonnie W. Ramsey, and Richard A. Kronmal
Proceedings of the American Thoracic Society 2007 4: 370-377.[Abstract] [Full Text] - Detection of Cystic Fibrosis Transmembrane Conductance Regulator Activity in Early-Phase Clinical Trials
- Steven M. Rowe, Frank Accurso, and John P. Clancy
Proceedings of the American Thoracic Society 2007 4: 387-398.[Abstract] [Full Text]
This article has been cited by other articles:
|
|
 |
|
  M. B. Dolovich 18F-Fluorodeoxyglucose Positron Emission Tomographic Imaging of Pulmonary Functions, Pathology, and Drug Delivery Proceedings of the ATS, August 15, 2009; 6(5): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Hirsh, J. Zhang, A. Zamurs, J. Fleegle, W. R. Thelin, R. A. Caldwell, J. R. Sabater, W. M. Abraham, M. Donowitz, B. Cha, et al. 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., April 1, 2008; 325(1): 77 - 88. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
