Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep;16(5):573-578.
doi: 10.1016/j.jcf.2017.04.011. Epub 2017 Apr 29.

A multiple reader scoring system for Nasal Potential Difference parameters

George M Solomon  1 , Bo Liu  2 , Isabelle Sermet-Gaudelus  3 , Isabelle Fajac  4 , Michael Wilschanski  5 , Francois Vermeulen  6 , Steven M Rowe  2
Affiliations

A multiple reader scoring system for Nasal Potential Difference parameters

George M Solomon et al. J Cyst Fibros. 2017 Sep.

Abstract

Background: Nasal Potential Difference (NPD) is a biomarker of CFTR activity used to diagnose CF and monitor experimental therapies. Limited studies have been performed to assess agreement between expert readers of NPD interpretation using a scoring algorithm.

Methods: We developed a standardized scoring algorithm for "interpretability" and "confidence" for PD (potential difference) measures, and sought to determine the degree of agreement on NPD parameters between trained readers.

Results: There was excellent agreement for interpretability between NPD readers for CF and fair agreement for normal tracings but slight agreement of interpretability in indeterminate tracings. Amongst interpretable tracings, excellent correlation of mean scores for Ringer's Baseline PD, Δamiloride, and ΔCl-free+Isoproterenol was observed. There was slight agreement regarding confidence of the interpretable PD tracings, resulting in divergence of the Ringers and Δamiloride, and ΔCl-free+Isoproterenol PDs between "high" and "low" confidence CF tracings.

Conclusion: A multi-reader process with adjudication is important for scoring NPDs for diagnosis and in monitoring of CF clinical trials.

Keywords: CFTR; Clinical trial outcomes; Nasal Potential Difference.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

None.

Figures

Fig. 1
Fig. 1
A. Training example of high confidence, interpretable CF tracing demonstrating lack of interfering artifacts, shifts, or catheter displacements with biologically plausible values and absence of missing or incomplete tracing portions. B. Training example of low-confidence, interpretable CF tracing due to excessive artifacts interfering with interpretability but displaying biologically plausible responses and the absence of missing or incomplete portions of the tracings. C. Training example of an uninterruptable CF tracing due to an incomplete chloride portion of the tracing due to catheter displacement with biologically implausible responses to amilioride and ATP controls. D. Training example of an unintepretable CF tracing due to excessive artifacts affecting the signal-to-noise ratio throughout with biologically implausible responses to amilioride and ATP controls.
Fig. 2
Fig. 2
A. Histogram showing higher level of agreement of “interpretability” for CF and non-CF amongst readers (n = 40 CF and non-CF tracings and n = 20 “indeterminate” tracings) reveals that CF and non-CF tracings display larger levels of complete agreement by readers regarding “interpretability” B. Histogram showing higher levels of agreement of “confidence” for sodium measures for CF and non-CF tracings amongst readers (n = 40 CF and non-CF tracings and n = 20 “indeterminate” tracings). C. Histogram showing higher level of agreement of “confidence” for chloride measures CF and non-CF tracings amongst readers (n = 40 CF and non-CF tracings and n = 20 “indeterminate” tracings).
See this image and copyright information in PMC

References

    1. Knowles MR, Carson JL, Collier AM, Gatzy JT, Boucher RC. Measurements of nasal transepithelial electric potential differences in normal human subjects in vivo. Am Rev Respir Dis. 1981;124(4):484–90. - PubMed
    1. Knowles MR, Buntin WH, Bromberg PA, Gatzy JT, Boucher RC. Measurements of transepithelial electric potential differences in the trachea and bronchi of human subjects in vivo. Am Rev Respir Dis. 1982;126(1):108–12. - PubMed
    1. Knowles MR, Stutts MJ, Yankaskas JR, Gatzy JT, Boucher RC., Jr Abnormal respiratory epithelial ion transport in cystic fibrosis. Clin Chest Med. 1986;7(2):285–97. - PubMed
    1. Standaert TA, Boitano L, Emerson J, Milgram LJ, Konstan MW, Hunter J, et al. Standardized procedure for measurement of nasal potential difference: an outcome measure in multicenter cystic fibrosis clinical trials. Pediatr Pulmonol. 2004;37(5):385–92. - PubMed
    1. Schuler D, Sermet-Gaudelus I, Wilschanski M, Ballmann M, Dechaux M, Edelman A, et al. Basic protocol for transepithelial nasal potential difference measurements. J Cyst Fibros. 2004;3(Suppl. 2):151–5. - PubMed

MeSH terms

Substances