A multicenter study of the effect of solution temperature on nasal potential difference measurements.
BACKGROUND
Nasal potential difference (PD) measurement quantifies the abnormal sodium and chloride transport that is characteristic of cystic fibrosis (CF) and has gained acceptance as both a diagnostic tool and outcome measure for new CF therapies. Because small changes in nasal PD-measured chloride transport are often an important component in evaluating new CF therapies, techniques to maximize sensitivity and reproducibility are essential.


OBJECTIVE
To determine if administration of warmed nasal PD solutions (37 degrees C), instead of room temperature solutions (22 degrees C), results in significant increase in nasal PD-measured transepithelial chloride transport.


METHODS
Multicenter, prospective, cross-over trial of repeated measurements of nasal PD at 22 degrees C and 37 degrees C.


RESULTS
Thirty-two healthy volunteers completed the study (four centers, each with 8 subjects). For 22 degrees C vs 37 degrees C, baseline (+/- SD) nasal PD (- 19.3 +/- 6.9 millivolts [mV] vs - 18.8 +/- 7.7 mV, p = 0.76), amiloride-sensitive PD (Delta PD, 10.4 +/- 5.6 mV vs 11.0 +/- 6.1 mV, p = 0.60), and low chloride response (Delta PD, - 10.0 +/- 8.0 mV vs - 8.0 +/- 7.1 mV, p = 0.13) were not statistically significantly affected by warming of solutions. Warming solutions to 37 degrees C dramatically increased the chloride transport response to isoproterenol (Delta PD, - 6.9 +/- 6.4 mV vs - 13.3 +/- 8.8 mV, p < 0.01) and the combined total response to low chloride and isoproterenol (Delta PD, - 16.9 +/- 9.5 mV vs - 21.3 +/- 11.9 mV, p = 0.01). The average increases observed with warming in isoproterenol and combined total responses were - 6.4 mV (95% confidence interval [CI], - 8.5 to - 4.3) and - 4.4 mV (95% CI, - 7.6 to - 1.1), respectively.


CONCLUSIONS
Performing nasal PD studies with solutions at 37 degrees C instead of 22 degrees C increases the observed total chloride response by approximately 25% and the isoproterenol-dependent chloride response by approximately 95%. The Cystic Fibrosis Foundation Therapeutics Development Network now recommends warming of solutions as a standard procedure for nasal PD protocols. Utilization of warmed solutions will standardize nasal PD techniques across centers and potentially increase the ability to identify therapies that result in small incremental improvements in CF transmembrane conductance regulator function.
Boyle
Michael P
MP
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. mboyle@jhmi.edu
Diener-West
Marie
M
Milgram
Laura
L
Knowles
Michael
M
Foy
Carla
C
Zeitlin
Pamela
P
Standaert
Thomas
T
D000328:Adult; D000584:Amiloride / Q000008:administration & dosage* / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018118:Chloride Channels / Q000187:drug effects*; D002712:Chlorides / Q000493:pharmacokinetics*; D016001:Confidence Intervals; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004232:Diuretics / Q000008:administration & dosage* / Q000494:pharmacology; D006361:Heating; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D007545:Isoproterenol / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism
D001993:Bronchodilator Agents; D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D000584:Amiloride; D007545:Isoproterenol