Employing the nasal potential difference as a diagnostic test for cystic fibrosis in neonates: Potential pitfalls

2002 ◽  
Vol 141 (2) ◽  
pp. 0295-0296 ◽  
Author(s):  
Erol A. Gaillard ◽  
Nigel J. Shaw ◽  
Nim V. Subhedar ◽  
Helen L. Wallace ◽  
Kevin W. Southern
Keyword(s):  
Cystic Fibrosis ◽  
Diagnostic Test ◽  
Potential Difference ◽  
Nasal Potential Difference

Uncertainty in the diagnosis of cystic fibrosis: Possible role of in vivo nasal potential difference measurements

1998 ◽  
Vol 132 (4) ◽  
pp. 596-599 ◽  
Author(s):  
David C. Wilson ◽  
Lynda Ellis ◽  
Julian Zielenski ◽  
Mary Corey ◽  
Wan F. Ip ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Potential Difference ◽  
Nasal Potential Difference

scholarly journals Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis

1997 ◽  
Vol 10 (9) ◽  
pp. 2018-2022 ◽  
Author(s):  
L.P. Ho ◽  
J.M. Samways ◽  
D.J. Porteous ◽  
J.R. Dorin ◽  
A. Carothers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Condition ◽  
Potential Difference ◽  
Nasal Potential Difference

Effect of Oral Digoxin, Topical Ouabain and Salbutamol on Transepithelial Nasal Potential Difference in Patients with Cystic Fibrosis

1995 ◽  
Vol 89 (3) ◽  
pp. 277-284 ◽  
Author(s):  
D. G. Peckham ◽  
A. Conn ◽  
C. Chotai ◽  
S. Lewis ◽  
A. J. Knox
Keyword(s):  
Cystic Fibrosis ◽  
Potential Difference ◽  
Sodium Absorption ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Control Subjects ◽  
Healthy Control ◽  
Nasal Potential Difference

1. Airway epithelium in cystic fibrosis is characterized by a defect in chloride secretion across the apical membrane and an increase in sodium absorption. The increased rate of sodium absorption can be inhibited in vitro by ouabain, a Na+-K+-ATPase inhibitor, and in cystic fibrosis patients the number and activity of nasal epithelial Na+-K+-ATPase pumps is increased. 2. We have performed a series of studies to determine whether drugs which modify airway epithelial Na+-K+-ATPase activity in vitro can modify nasal potential in cystic fibrosis patients in vivo. As transepithelial nasal potential difference measurements were used to study the effect of drug modulation of airway epithelial ion transport in vivo, the repeatability of the technique was first evaluated. In order to assess the effectiveness of the technique used for measuring nasal potential difference, a pilot study was carried out using topical amiloride, a drug which has previously been shown to inhibit airway epithelium sodium transport in vivo. We then studied the effects of ouabain and digoxin, two inhibitors of Na+-K+-ATPase, and salbutamol, a drug which activates Na+-K+-ATPase, on nasal potential difference. 3. In study 1, nasal potential difference measurements were repeated on non-consecutive days in 20 patients with cystic fibrosis and 20 healthy individuals. Healthy subjects had a mean (SEM) potential difference value of −19.5 (0.9) mV, with a 95% range for a single estimate of 75–133%. In patients with cystic fibrosis, the mean (SEM) potential difference was −40.4 (2.1) mV, with a 95% range for a single estimate of 74–136%. 4. In an initial pilot study, the effect of topical amiloride on nasal potential difference was investigated on two consecutive days in four cystic fibrosis patients and four healthy control subjects, in a double-blind, placebo-controlled, randomized cross-over study. Nasal transepithelial potential was measured before and at 5, 15, 30, 45 and 60 min after the intranasal administration of 0.4 ml of a fine spray of 1 mmol/l amiloride or 0.9% saline placebo to both nostrils. Amiloride was associated with a maximal reduction in nasal potential difference at 15 min of 49% and 41% in cystic fibrosis patients and control subjects, respectively. Compared with saline, the amiloride response was significant in both groups (P < 0.025). 5. In study 2, the effect of topical ouabain and salbutamol on nasal potential difference was investigated in ten cystic fibrosis patients and ten healthy control subjects, in a double-blind, placebo-controlled, randomized cross-over study. Nasal transepithelial potential was measured before and at 5, 15, 30, 45 and 60 min after the intranasal administration of either 0.4 ml of a fine spray of 5 mg/ml salbutamol, 0.25 mg/ml ouabain or 0.9% saline placebo to both nostrils. There was no significant change in nasal potential difference with either ouabain, salbutamol or placebo in either healthy control subjects or patients with cystic fibrosis. 6. In study 3, we performed a randomized, double-blind, placebo-controlled cross-over study of oral digoxin on nasal potential difference, spirometry and sweat electrolytes for 2 weeks in 11 patients with cystic fibrosis. During the treatment period, patients had a mean (range) serum digoxin level after the first and second week of therapy of 0.9 (0.3–1.4) μg/l and 1.1 (0.4–2.2) μg/l, respectively. There was no significant difference in the change in nasal potential difference measurements, forced expiratory volume in 1 s and sweat Na/Cl concentrations between the digoxin and placebo trial periods. 7. In conclusion, neither topical ouabain nor systemic digoxin had any effect on nasal potential difference in cystic fibrosis. Inhibitors of Na+-K+-ATPase are therefore unlikely to find a role in the treatment of cystic fibrosis. The lack of a detrimental effect of salbutamol on nasal potential difference is reassuring, as β-agonists are widely used in patients with cystic fibrosis.

scholarly journals Nasal Potential Difference in Cystic Fibrosis considering SevereCFTRMutations

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ronny Tah Yen Ng ◽  
Fernando Augusto de Lima Marson ◽  
Jose Dirceu Ribeiro ◽  
Antonio Fernando Ribeiro ◽  
Carmen Silvia Bertuzzo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Statistical Analysis ◽  
Gold Standard ◽  
Healthy Subjects ◽  
Gene Sequencing ◽  
Potential Difference ◽  
Healthy Controls ◽  
Exact Tests ◽  
Sweat Chloride ◽  
Nasal Potential Difference

The gold standard for diagnosing cystic fibrosis (CF) is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD) test.CFTRgene sequencing can identifyCFTRmutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-IIICFTRmutations (10 patients) (G1), CF patients with classes IV-VICFTRmutations (five patients) (G2), and 21 healthy subjects (G3). The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis,χ2, and Fisher’s exact tests,α=0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-IIICFTRmutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects.

scholarly journals Nasal potential difference measurements in diagnosis of cystic fibrosis: An international survey

2014 ◽  
Vol 13 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Lutz Naehrlich ◽  
Manfred Ballmann ◽  
Jane Davies ◽  
Nico Derichs ◽  
Tanja Gonska ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Potential Difference ◽  
International Survey ◽  
Nasal Potential Difference

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

2004 ◽  
Vol 37 (5) ◽  
pp. 385-392 ◽  
Author(s):  
Thomas A. Standaert ◽  
Louis Boitano ◽  
Julia Emerson ◽  
Laura J.H. Milgram ◽  
Michael W. Konstan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Trials ◽  
Outcome Measure ◽  
Potential Difference ◽  
Nasal Potential Difference

Amiloride-insensitive nasal potential difference varies with the menstrual cycle in cystic fibrosis

2007 ◽  
Vol 42 (6) ◽  
pp. 519-524 ◽  
Author(s):  
Neil B. Sweezey ◽  
David Smith ◽  
Mary Corey ◽  
Lynda Ellis ◽  
Susan Carpenter ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Menstrual Cycle ◽  
Potential Difference ◽  
Nasal Potential Difference

scholarly journals Intestinal current measurement and nasal potential difference to make a diagnosis of cases with inconclusive CFTR genetics and sweat test

2020 ◽  
Vol 7 (1) ◽  
pp. e000736 ◽  
Author(s):  
Rebecca Minso ◽  
Angela Schulz ◽  
Christian Dopfer ◽  
Nadine Alfeis ◽  
Andrea van Barneveld ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Symptoms ◽  
Potential Difference ◽  
Sweat Test ◽  
Transmembrane Conductance Regulator ◽  
Coding Region ◽  
Transmembrane Conductance ◽  
Related Disorder ◽  
False Positive Diagnosis ◽  
Nasal Potential Difference

BackgroundNasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and CFTR genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).MethodsNPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.ResultsWe assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and CFTR genetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with a CFTR genotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identified CFTR mutation. If two CFTR sequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range.ConclusionThe majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-type CFTR coding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region of CFTR or elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.

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