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J Cyst Fibros. 2019 Nov 4. pii: S1569-1993(19)30899-9. doi: 10.1016/j.jcf.2019.09.015. [Epub ahead of print]

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

Author information

1
Centre Maladies Rares Mucoviscidose, Hôpital Universitaire Necker-Enfants Malades, Assistance-Publique Hôpitaux de Paris, Paris, France.
2
Bio-statistics Department, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
3
Hadassah Medical center, Hebrew University, Jerusalem, Israel.
4
AP-HP, Hopital Cochin, Physiology Department, Paris, France; UPRES EA 2511, Paris, France; Université Paris Sorbonne, Paris, France.
5
CF and Chronic Lung Infection, National Heart and Lung Institute, Imperial College London, UK; Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
6
Bio-statistics Department, Hôpital Universitaire Necker-Enfants Malades, Paris, France; Université Paris Sorbonne, Paris, France.
7
Centre Maladies Rares Mucoviscidose, Hôpital Universitaire Necker-Enfants Malades, Assistance-Publique Hôpitaux de Paris, Paris, France; Université Paris Sorbonne, Paris, France; Institut Necker-Enfants Malades. INSERM U1151, Paris, France. Electronic address: isabelle.sermet@nck.aphp.fr.

Abstract

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

PMID:
31699569
DOI:
10.1016/j.jcf.2019.09.015

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