Chest
Original ResearchCystic FibrosisAn International Randomized Multicenter Comparison of Nasal Potential Difference Techniques
Section snippets
Study Design
Each institution obtained approval for the NPD comparison in human subjects from their respective institutional review board or ethics committee, and written informed consent was obtained from all study subjects. The University of Alabama at Birmingham's institutional review board approved the central analysis of the data. The subjects then underwent NPD testing using the other methodology at least 1 day later, a period sufficient to wash out the effects of amiloride and isoproterenol. Normal
Results
A total of 26 subjects from six centers underwent randomization and completed the protocol. The mean age of the subjects was 39 (±12) years, and 78% were women (Table 1). Representative tracings are provided in Figure 2 and include examples of transient excursions and sustained breaks (Fig 2A). Comparison of tracings obtained using the agar catheter method with those obtained using the perfusion method in the same nostril of the same subject revealed that tracings using the agar catheter were
Discussion
To our knowledge, this study represents the first rigorous, randomized, controlled, multicenter comparison of methods for measurement of the NPD. Our results demonstrate that an agar catheter yields significantly enhanced data quality compared with the perfusion catheter. The improvements in signal quality and tracing stability address important limitations of the NPD assay that have adversely affected reproducibility in previous studies.19, 24 These findings were observed both in centers with
Conclusions
A number of CFTR modulators that can be used potentially to improve the underlying defect in CFTR activity are being evaluated in clinical testing, including potentiators of surface-localized CFTR,11 correctors of ΔF508 CFTR processing (clinicaltrials.gov, NCT00865904), and suppressors of premature termination codons.8, 9, 10, 23 The development of each of these approaches has used proof-of-concept studies based on NPD measurements. Given the importance of this biomarker in the measurement of
Acknowledgments
Author contributions: Dr Rowe has access to all data and takes full responsibility for data analysis and accuracy.
Dr Solomon: contributed to the development and pilot testing of the agar catheter, the performance of NPDs, the supervision of statistical analysis, and the writing of the manuscript, and was one of the overall principal investigators.
Dr Konstan: contributed as principal investigator at his site.
Dr Wilschanski: contributed as principal investigator at his site.
Dr Billings:
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Funding/Support: This research was funded by the US National Institutes of Health [Grants 1K23DK075788-01 and 1R03DK084110-01 (to Dr Rowe) and Grant 1P30DK072482-01A1 (to Eric J. Sorscher)] and the Cystic Fibrosis Foundation [Grants CLANCY05Y2 (Drs Clancy and Rowe) and RAMSEY03Y0 (to the Therapeutics Development Network Coordinating Center)].
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