Clinical Phenotype and Genotype of Children with Borderline Sweat Test and Abnormal Nasal Epithelial Chloride Transport

Abstract

Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.

CFTR biomarkers: time for promotion to surrogate end-point

“…25 studies consistently show a statistically significant difference in chloride and sodium conductance between patients with cystic fibrosis and healthy controls. In patients with ''questionable'' cystic fibrosis, NPD composite scores provided a highly sensitive tool to diagnose patients as ''CF-likely'' and ''CF-unlikely'', with both cohorts having significantly different disease presentation [39,[77][78][79]. Data from studies with ataluren, ivacaftor, the CFTR corrector VX-809 and gene therapy confirm that NPD is a responsive endpoint.…”

Nasal potential difference of carriers of the W493R ENaC variant with non-cystic fibrosis bronchiectasis

“…NPD measurements were performed according to the Standard Operating Procedure NPD_EU001, version 1.7 (March 2013) of the European Cystic Fibrosis Society Diagnostic Network Working Group, which primarily differs from a publicly available protocol [5] by superfusion of room temperature solutions through a Marquat catheter (model I0202US; Marquat Genie Biomedical, Boissy-Saint-Leger, France). Two subjects presented normal NPD tracings, and two subjects showed a normal response to amiloride, but only a minute response upon exposure to chloride-free solution consistent with the diagnosis of a CFTR-related disorder [6,7]. However, one subject, a 58-year old female with non-CF bronchiectasis and underlying asthma complicated by allergic bronchopulmonary aspergillosis, produced a tracing suggestive of a hyperactive ENaC.…”

A semi-blinded study comparing 2 methods of measuring nasal potential difference: Subcutaneous needle versus dermal abrasion

“…We used 3 different criteria to discriminate between CF and non-CF, taking into account a total chloride response less than − 10 mV [12,15,16], and Sermet and Wilschanski composite scores as described in the original articles, being less than 0.27 for Ser score (developed with Abr method) and more than 0.7 for Wils score (developed with Ndl method) in the case of CF [17,18]. Previous papers have underlined the importance of taking into account the combined response on the different solutions, showing the ENaC-response on the Amilo solution and the net effect of chloride efflux due to passive (chloride-free solution) and active (cAMP-activated CFTR activity by isoproterenol) chloride transport [17,18]. Some CF patients can have a subnormal chloride-response but an increased sodium-absorption.…”

“…A NPD tracing was scored as CF if at least 2 of the 3 diagnostic criteria were fulfilled, namely: a total chloride response (ie. NPD-response after perfusion with solution #3 + #4, being Cl-Free and Iso) of less than − 10 mV [12,15,16], Wilschanski score = (e (total chloride response/Amilo response) ) N 0.7 (Wils score) [17] and Sermet score = [− 0.11(delta chloride free + Iso) − 0.05(Amilo response)] b 0.27 (Ser score) [18]. Otherwise, they were scored as non-CF.…”