Cystic Fibrosis Diagnosis in Newborns, Children, and Adults

Carlo Castellani, MD; Barry Linnane, MB, BCh, BAO, DCH, MRCPI, MRCPCH, MD; Iwona Pranke, PhD; Federico Cresta, MD; Isabelle Sermet-Gaudelus, MD, PhD; Daniel Peckham, MD

Disclosures

Semin Respir Crit Care Med. 2019;40(6):701-714. 

In This Article

Nasal Potential Difference

Nasal potential difference (NPD) measures electric potential divergence between a subcutaneous reference electrode and a Cl electrode connected to a nasal catheter.[156] The probe is placed under the inferior turbinate where maximal negative voltage is recorded, and maintained in this position for the duration of the test. Recordings are made during continuous flow of salt solutions at a rate of 5 mL/min. Following a baseline period, solutions are perfused to investigate CFTR function: (1) amiloride in saline, to block the epithelial sodium channel (ENaC); (2) Cl-free saline in presence of amiloride to drive Cl secretion and (3) isoproterenol (10 μM) in a Cl-free saline solution containing amiloride to activate CFTR. NPD measurement therefore provides information on both Na+ absorption and Cl secretion. In CF epithelia there is heightened ENaC-mediated Na+ absorption due to absent or dysfunctional CFTR and the resultant baseline potential difference is more negative. The larger change in potential difference is seen with application of amiloride, whereas there is minimal or no change upon stimulation of Cl secretion through CFTR-dependent pathways (Figure 1).

Figure 1.

Normal and cystic fibrosis nasal potential difference tracings.

This test has been standardized and validated for diagnostic accuracy through joint efforts of the European Clinical Trial Network and the US Therapeutic Diagnostic Network.[157] Despite a relative high intrasubject variability, NPD scores based on both the response to amiloride and Cl secretion provide a highly sensitive tool to diagnose patients as "CF-likely'' and ''CF-unlikely."[149,150] Heterozygotes, pancreatic sufficient CF patients and individuals with CFTR-related diseases tend to show overlapping results, thus impairing the diagnostic value of this test in individual cases with borderline CFTR function.[158]

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