Insights into the variability of nasal potential difference, a biomarker of CFTR activity

J Cyst Fibros. 2020 Jul;19(4):620-626. doi: 10.1016/j.jcf.2019.09.015. Epub 2019 Nov 4.


Background: Nasal potential difference (NPD) is used to evaluate CFTR function in vivo. We aimed to evaluate the intrasubject and intersubject variability of NPD measurements.

Methods: We reviewed NPD tracings of 116 patients with CF enrolled in the placebo arm of a multicenter study. Patients carried at least one nonsense mutation and underwent repeated NPD tests every 16 weeks. NPD parameters included basal potential difference (basal PD), inhibition of sodium absorption by amiloride (Δ Amiloride), chloride (Cl-) transport in response to a Cl--free solution (Δ Low Cl-), isoproterenol (Δ Isoproterenol), the sum of Δ Low Cl- and Δ Isoproterenol (Δ Low Cl--Isoproterenol) and ATP (Δ ATP).

Results: Basal PD and Δ Amiloride displayed the highest variabilities, mainly stemming from intercenter and intrasubject effect. Δ Low Cl-, Δ Isoproterenol and Δ Low Cl--Isoproterenol demonstrated a large intrasubject variability but a smaller intersubject variability. The intrasubject measurement variability for Δ Low Cl--Isoproterenol, was within ± 7.2 mV with 95% probability. It was greater in patients reporting ongoing pulmonary exacerbations.

Conclusions: The large intercenter variability of basal PD and Δ Amiloride highlights the operator-dependent aspect of these measurements. A difference greater than 7.2 mV in Δ Low Cl--Isoproterenol in a given patient on CFTR modulator can be attributed, with 95% probability, to a treatment effect rather than to the variability inherent in the measurement.

Keywords: Biomarker; Cystic Fibrosis; Nasal potential difference.

MeSH terms

  • Adult
  • Amiloride / pharmacology*
  • Biological Transport / drug effects*
  • Bronchodilator Agents / pharmacology
  • Chlorides / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator* / metabolism
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / physiopathology
  • Epithelial Sodium Channel Blockers / pharmacology
  • Female
  • Humans
  • Isoproterenol / pharmacology*
  • Male
  • Membrane Potentials*
  • Mutation
  • Nasal Mucosa* / metabolism
  • Nasal Mucosa* / physiopathology
  • Observer Variation
  • Sodium / metabolism


  • Bronchodilator Agents
  • Chlorides
  • Epithelial Sodium Channel Blockers
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Amiloride
  • Sodium
  • Isoproterenol