Standardized procedure for measurement of nasal potential difference: An outcome measure in multicenter cystic fibrosis clinical trials

Abstract

Patients with cystic fibrosis (CF) can be discriminated from healthy subjects by measurement of the nasal potential difference, which has become a useful outcome measure for therapies directed toward correcting defective electrolyte transport in CF. A standard operating procedure was developed by a CF Foundation clinical trials network, to be followed by all sites performing collaborative studies. Key variables in the measurement included type of voltmeter, exploring probe, reference electrodes, and solutions used to assess both sodium transport and chloride conductance. Eight sites submitted data on 3-8 normal and 4-5 CF subjects. Baseline voltage, an index of sodium transport, was -18.2 +/- 8.3 mV (mean +/- SD) for normals, and -45.3 +/- 11.4 mV for CF patients. There was no CFTR-mediated chloride secretion in CF subjects, as evidenced by the lack of response to perfusion with zero chloride + beta agonist solutions (+3.2 +/- 3.5 mV) vs. that in normals (-23.7 +/- 10.2 mV). The standardized nasal potential difference measurement minimizes variability between operators and study sites. Valid and consistent results can be attained with trained operators and attention to technical details. These data demonstrate the procedure to be sufficient for multicenter studies in the CF Foundation network.

Exercise reduces airway sodium ion reabsorption in cystic fibrosis but not in exercise asthma

“…CFTR channel inactivity is associated with increased Na + reabsorption [24]. Catecholamine-stimulated cAMP production might increase Na + channel activity even further [4], which might exaggerate the depletion of airway lining fluid caused by the defective CFTR.…”

“…Our protocols for measuring nasal potential differed from the standard procedures for multicentre CF diagnosis [24], which would also provide measures for Ca 2+ activated Cl -channels.…”

Human cystic fibrosis airway epithelia have reduced Cl − conductance but not increased Na + conductance

“…Loss of anion conductance has been apparent in nearly all studies of differentiated CF airway epithelial cultures (9,10,13,14). In addition, some studies showed an increased short-circuit current (Isc) and voltage under basal conditions (basal Isc and basal Vt, respectively) and increased reductions with amiloride application (ΔIsc amil and ΔVt amil , respectively) (7).…”

Biochemical and Molecular Genetic Testing Used in the Diagnosis and Assessment of Cystic Fibrosis

“…Properly conducted NPD testing at a research center can provide valuable information for diagnosis when clinical evidence is not clear-cut; however, access to the test is limited. Because there are no clear reference values, validation studies, or standardized technical protocols for NPD testing for diagnostic purposes, the test should be used only to provide contributory evidence in a diagnostic evaluation (Standaert et al, 2004).…”