Abstract
Background: Nasal potential difference (NPD) test has long been used to assist in the diagnosis of Cystic Fibrosis (CF) and more recently as an outcome measure in clinical trials of new CF therapies. This test has also been adapted to the mouse nose. Objectives: We aimed at evaluating variability of the NPD measurements in CF patients displaying two severe CFTR mutations and in sex-matched healthy controls. NPD recorded from F508del-CF and normal wild-type mice were also compared. Methods and results: In each setting, tests were performed by a single qualified operator. In the clinical setting, the latest standardized operation protocol of the CF foundation was followed. A total of 80 tracings were obtained from 10 patients (23.2 y; range 14 to 32) and 10 healthy subjects (34 y; range 24 to 53), each tested twice, in both nostrils. Two CF and two controls were excluded from the statistical data analysis due to the presence of a single non interpretable NPD tracing (4/80, 5%). To achieve equal sample size, tests were obtained from 8 CF mice and normal wild-type. Comprehensive multivariate analysis of paired data showed a good reproducibility of NPD parameters in the clinical and the preclinical setting; lower variability was observed in mice. However, 95% repeatability limits of NPD parameters were large indicating a large measurement error, poor precision and low within-subject repeatability. In both settings, chloride secretion was shown to be the most reproducible and repeatable parameter. Conclusion: In human as in mice, NPD showed good reproducibility but limited within-subject repeatability.
Highlights
Electrical potential difference (PD) across the mucous nasal epithelia has been used for more than two decades to assess cystic fibrosis (CF) transmembrane conductance regulator (CFTR) activity and to assist in the diagnosis of Cystic Fibrosis (CF) [1]
A total of 80 nasal PD tracings were obtained from 10 patients and 10 healthy subjects tested twice, in quick succession, in both nostrils
Even though the three other tracings obtained from these two patients and two controls were considered of good quality, the 4 corresponding participants were excluded from the statistical analysis of repeatability of the nasal PD test
Summary
Electrical potential difference (PD) across the mucous nasal epithelia has been used for more than two decades to assess cystic fibrosis (CF) transmembrane conductance regulator (CFTR) activity and to assist in the diagnosis of CF [1]. Substantial efforts have been devoted by the CF Foundation Therapeutics-Therapeutics Development Network (CFFT-TDN) and by the Clinical Trial Network of the European Cystic Fibrosis Society (ECFSCTN) to perfect a standardized operating protocol (SOP) to be adopted by CF centers worldwide. Nasal potential difference (NPD) test has long been used to assist in the diagnosis of Cystic Fibrosis (CF) and more recently as an outcome measure in clinical trials of new CF therapies. This test has been adapted to the mouse nose. Comprehensive multivariate analysis of paired data showed a good reproducibility of NPD parameters in the clinical and the preclinical setting; lower variability was observed in mice. Conclusion: In human as in mice, NPD showed good reproducibility but limited within-subject repeatability
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