An international randomized multicenter comparison of nasal potential difference techniques.
BACKGROUND
The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials.


METHODS
To determine whether a nonperfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at six different centers.


RESULTS
Artifact frequency was reduced by 75% (P < .001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, because Δ zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (224.2 ± 12.9 mV with agar vs 18.2 ± 9.1 mV with perfusion, P < .05).


CONCLUSIONS
The agar nasal catheter approach demonstrates superior reliability compared with the perfusion nasal catheter method for measurement of NPD. This nonperfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials.
Solomon
George M
GM
University of Alabama at Birmingham, Birmingham, AL 35294-0006, USA.
Konstan
Michael W
MW
Wilschanski
Michael
M
Billings
Joanne
J
Sermet-Gaudelus
Isabelle
I
Accurso
Frank
F
Vermeulen
François
F
Levin
Elina
E
Hathorne
Heather
H
Reeves
Ginger
G
Sabbatini
Gina
G
Hill
Aubrey
A
Mayer-Hamblett
Nicole
N
Ashlock
Melissa
M
Clancy
John Paul
JP
Rowe
Steven M
SM
D000328:Adult; D000362:Agar; D000704:Analysis of Variance; D016477:Artifacts; D002404:Catheterization / Q000379:methods*; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009297:Nasal Mucosa / Q000502:physiology*
D005782:Gels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000362:Agar
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