TY - JOUR
T1 - A multicenter study of the effect of solution temperature on nasal potential difference measurements
AU - Boyle, Michael P.
AU - Diener-West, Marie
AU - Milgram, Laura
AU - Knowles, Michael
AU - Foy, Carla
AU - Zeitlin, Pamela
AU - Standaert, Thomas
N1 - Funding Information:
Funded by the Cystic Fibrosis Foundation Therapeutics Development Network, the Cystic Fibrosis Foundation, and National Institutes of Health grant NCRR-00052 (to Johns Hopkins School of Medicine).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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. Study objective: To determine if administration of warmed nasal PD solutions (37°C), instead of room temperature solutions (22°C), results in significant increase in nasal PD-measured transepithelial chloride transport. Design: Multicenter, prospective, cross-over trial of repeated measurements of nasal PD at 22°C and 37°C. Results: Thirty-two healthy volunteers completed the study (four centers, each with 8 subjects). For 22°C vs 37°C, baseline (± SD) nasal PD (- 19.3 ± 6.9 millivolts [mV] vs - 18.8 ± 7.7 mV, p = 0.76), amiloride-sensitive PD (ΔPD, 10.4 ± 5.6 mV vs 11.0 ± 6.1 mV, p = 0.60), and low chloride response (ΔPD, - 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°C dramatically increased the chloride transport response to isoproterenol (ΔPD, - 6.9 ± 6.4 mV vs - 13.3 ± 8.8 mV, p < 0.01) and the combined total response to low chloride and isoproterenol (ΔPD, - 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°C instead of 22°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.
AB - 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. Study objective: To determine if administration of warmed nasal PD solutions (37°C), instead of room temperature solutions (22°C), results in significant increase in nasal PD-measured transepithelial chloride transport. Design: Multicenter, prospective, cross-over trial of repeated measurements of nasal PD at 22°C and 37°C. Results: Thirty-two healthy volunteers completed the study (four centers, each with 8 subjects). For 22°C vs 37°C, baseline (± SD) nasal PD (- 19.3 ± 6.9 millivolts [mV] vs - 18.8 ± 7.7 mV, p = 0.76), amiloride-sensitive PD (ΔPD, 10.4 ± 5.6 mV vs 11.0 ± 6.1 mV, p = 0.60), and low chloride response (ΔPD, - 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°C dramatically increased the chloride transport response to isoproterenol (ΔPD, - 6.9 ± 6.4 mV vs - 13.3 ± 8.8 mV, p < 0.01) and the combined total response to low chloride and isoproterenol (ΔPD, - 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°C instead of 22°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.
KW - Chloride transport
KW - Cystic fibrosis
KW - Cystic fibrosis transmembrane conductance regulator
KW - Nasal potential difference
KW - Respiratory epithelium
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U2 - 10.1378/chest.124.2.482
DO - 10.1378/chest.124.2.482
M3 - Article
C2 - 12907532
AN - SCOPUS:0043234162
SN - 0012-3692
VL - 124
SP - 482
EP - 489
JO - CHEST
JF - CHEST
IS - 2
ER -