Nasal potential difference outcomes support diagnostic decisions in cystic fibrosis

Abstract

Background: When cystic fibrosis (CF) is suspected Nasal Potential Difference (NPD) measurements are proposed to support controversial diagnosis: we investigated appropriate outcomes at the CF Centre of Verona.

Subjects/methods: NPD were measured in 196 subjects: 50 non-CF, 65 classical CF (the reference group) and 81 with uncertain CF (case group). Discriminating power was determined by comparison between several outcomes from the CF reference group versus non-CF: basal, amiloride, 0Cl, isoproterenol, ATP, Delta-amiloride, Delta-0Cl, Delta-isoproterenol, Delta-ATP, Delta-isoproterenol+Delta-0Cl, Wilschanski Index (WI) and Sermet score (SS). The most appropriate cut-off values for variables with the best discriminating power were then applied to the case group. Descriptive statistics, logistic regression models and ROC curve analysis were applied.

Results: WI and SS were the most powerful in discriminating CF from non-CF subjects. In the reference group sensitivity of the 0.82 WI cut-off was 98%, specificity 96%; both sensitivity and specificity of the -0.44 SS cut-off value were 100%. For the case group, WI and SS were, respectively, consistent with CF diagnosis in 94% and 92% of the cases.

Conclusions: Formulae have the highest discriminating power and can support the diagnosis in uncertain cases; they should be utilized for standardized interpretation of NPD for diagnosis and possibly for clinical research.

Keywords: CFTR genetic test; CFTR related disorders; Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator; Diagnosis; Nasal potential difference measurements; Sweat test.