Nasal potential difference: Best or average result for CFTR function as diagnostic criteria for cystic fibrosis?

BackgroundThe current practice of averaging the nasal potential difference (NPD) results of right and left nostril measurements reduce inter-individual variability but may underestimate individual CFTR function.MethodsBest NPD response to Cl−-free and isoproterenol perfusion (= largest ΔPD0Cl/Iso) from the right and left nostril was compared to the average result in 13 cystic fibrosis (CF), 78 query-CF patients and 22 healthy controls from 2 cohorts.ResultsDespite moderate to good correlation (p < 0.001) between right and left measured ΔPD0Cl/Iso, we observed large differences in some individuals. A comparison of average versus best ΔPD0Cl/Iso showed only moderate agreement (Giessen κ = 0.538; Toronto κ = 0.607). Averaging ΔPD0Cl/Iso showed a lower composite chloride response compared to best ΔPD0Cl/Iso and altered diagnostic NPD interpretation in 30 of 113 (27%) subjects.ConclusionsThe current practice of averaging the NPD results of right and left nostril measurements leads to an underestimation of the individual CFTR function and should be reconsidered.