Does Integration of Various Ion Channel Measurements Improve Diagnostic Performance in Cystic Fibrosis

Rationale: The diagnosis of cystic fibrosis (CF) may remain inconclusive despite comprehensive evaluation.Objectives: Determine whether combined ion channel measurements (C-ICMs) obtained from different end-organ epithelia can help diagnose CF.Methods: Prospective enrollment of (1) a training sample of 156 non-CF subjects and 107 patients with CF, and (2) a validation cohort of 202 patients with single-organ CF-like phenotypes. All subjects had genotyping, sweat test, and nasal potential difference (NPD). Principal components analysis was applied to derive various candidate C-ICMs by combining sweat chloride plus every one or two combination(s) of four NPD parameters (maximal potential difference [MaxPD], change in potential difference in response to perfusion with amiloride [ΔAmil], change after chloride-free and isoproterenol perfusion [ΔCl-free+Iso], and total change in potential difference [ΔAmil+Cl-free+Iso]).Measurements and Main Results: The best of the 10 candidate C-ICMs, which combined sweat chl...