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. Study objective: To determine if administration of warmed nasal PD solutions (37degreesC), instead of room temperature solutions (22degreesC), results in significant increase in nasal PD-measured transepithelial chloride transport. Design: Multicenter, prospective, cross-over trial of repeated measurements of nasal PD at 22degreesC and 37degreesC. Results: Thirty-two healthy volunteers completed the study (four centers, each with 8 subjects). For 22degreesC vs 37degreesC, baseline (+/- SD) nasal PD (- 19.3 +/- 6.9 millivolts [mV] vs - 18.8 +/- 7.7 mV, p = 0.76), amiloride-sensitive PD (DeltaPD, 10.4 +/- 5.6 mV vs 11.0 +/- 6.1 mV, p = 0.60), and low chloride response (DeltaPD, - 10.0 +/- 8.0 mV vs - 8.0 +/- 7.1 mV, p = 0.13) were not statistically significantly affected by warming of solutions. War ming solutions to 37degreesC dramatically increased the chloride transport response to isoproterenol (DeltaPD, - 6.9 +/- 6.4 mV vs - 13.3 +/- 8.8 mV, p < 0.01) and the combined total response to low chloride and isoproterenol. (DeltaPD, - 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 37degreesC instead of 22degreesC 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.