Clinical application of transepithelial potential difference measurements in cystic fibrosis

Sauder, Russell A.; Chesrown, Sarah E.; Loughlin, Gerald M.

doi:10.1016/s0022-3476(87)80453-5

Cited by 35 publications

(14 citation statements)

References 16 publications

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“…The nasal transepithelial PD has been used to quantify respiratory transepithelial sodium transport in patients with cystic fibrosis [11,[20][21][22], and to assess the effects of over-or under-expression of the amiloride-sensitive sodium channel on this transport mechanism [23,24]. Nasal and airways epithelium exhibit similarities in membrane bioelectric properties and ion transport, suggesting that nasal PD may represent an estimate of vectorial sodium transport in the more distal airways [11].…”

Section: Discussionmentioning

confidence: 99%

High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects

Sartori¹,

Duplain²,

Lepori³

et al. 2004

Eur Respir J

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High-altitude pulmonary oedema (HAPE) occurs in predisposed individuals at altitudes w2,500 m. Defective alveolar fluid clearance secondary to a constitutive impairment of the respiratory transepithelial sodium transport contributes to its pathogenesis. Hypoxia impairs the transepithelial sodium transport in alveolar epithelial type II cells in vitro. If this impairment is also present in vivo, high-altitude exposure could aggravate the constitutive defect in sodium transport in HAPE-prone subjects, and thereby further facilitate pulmonary oedema.Therefore, the aim of the current study was to measure the nasal potential difference (PD) in 21 HAPE-prone and 29 HAPE-resistant subjects at low altitude and 30 h after arrival at high altitude (4,559 m).High-altitude exposure significantly decreased the mean¡SD nasal PD in HAPEprone (18.0¡6.2 versus 12.5¡6.8 mV) but not in HAPE-resistant subjects (25.6¡9.4 versus 22.9¡9.2 mV). This altitude-induced decrease was not associated with an altered amiloride-sensitive fraction, but was associated with a significantly lower amilorideinsensitive fraction of the nasal PD.These findings provide evidence in vivo that an environmental factor may impair respiratory transepithelial sodium transport in humans. They are consistent with the concept that in high-altitude pulmonary oedema-susceptible subjects, the combination of a constitutive and an acquired defect in this transport mechanism facilitates the development of pulmonary oedema during high-altitude exposure. High-altitude pulmonary oedema (HAPE) is a lifethreatening condition that occurs in predisposed but otherwise healthy individuals at altitudes w2,500 m. Augmented alveolar fluid flooding related to exaggerated hypoxic pulmonary vasoconstriction plays an important role in its pathogenesis, secondary to endothelial dysfunction and sympathetic overactivity [1][2][3]. However, recent observations indicate that this mechanism may not be sufficient to cause high-altitude pulmonary oedema [4].Active sodium transport across the alveolar epithelium plays an important role in keeping the lungs free of fluid [5,6]. In alveolar epithelial cells, sodium enters the apical membrane primarily through the amiloride-sensitive cation channels (mainly ENaC), and is then transported across the basolateral membrane into the interstitium by the ouabain-inhibitable Na-K-ATPase [5][6][7][8].A genetic impairment of the transepithelial sodium transport mechanism facilitates pulmonary oedema in transgenic mice [9,10] and possibly also in humans, as suggested by HAPE-prone subjects who have a smaller nasal potential difference (PD) (an indirect marker of vectorial sodium transport in the distal airways) [11] than mountaineers resistant to this condition [12]. Consistent with this concept, prophylactic stimulation of this transport mechanism with the b 2 -adrenergic agonist salmeterol, at a dose that stimulates respiratory sodium transport in vitro [8] and increases alveolar fluid clearance in vivo [13], decreased the incidence of HAPE in h...

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Section: Discussionmentioning

confidence: 99%

High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects

Sartori¹,

Duplain²,

Lepori³

et al. 2004

Eur Respir J

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“…In fact, at present, only DNA analysis can be considered as a gold standard to assess the diagnostic value of NPD in doubtful cases of CF. Even if measurement of NPD has been advocated as a complementary diagnostic test in patients with a doubtful diagnosis of CF [6], at present, little experience is available in such cases. For instance, to our knowledge, this is the first report of pathological NPD values in a group of CF patients with a borderline sweat test and carrying CF gene mutations other than 3849+10KbC→T and G551S.…”

Section: Discussionmentioning

confidence: 99%

“…The impaired ion transport of CF respiratory epithelial function can be studied in vivo by measuring the potential difference in nasal mucosa (NPD), a noninvasive technique first proposed by KNOWLES et al [3] and, subsequently, by others [4,5]. NPD makes it possible to discriminate CF patients from normal subjects, CF obligate heterozygotes, and patients with a variety of respiratory disorders [4], so that the technique has been proposed as a useful diagnostic tool in CF [6].…”

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confidence: 99%

Nasal potential difference in cystic fibrosis patients presenting borderline sweat test

Delmarco

Pradal²,

Cabrini³

et al. 1997

Eur Respir J

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The diagnosis of cystic fibrosis (CF) can be difficult if the sweat test and routine deoxyribonucleic acid (DNA) analysis are inconclusive. Under these circumstances, measurement of nasal potential difference (NPD) was proposed as a complementary diagnostic tool, as demonstrated in subjects bearing the G551S or 3849+10KbC→T mutations. The purpose of the present study was to verify the diagnostic value of this technique in CF patients with a borderline sweat test. NPD was measured in 18 patients with a borderline sweat test, in whom CF diagnosis was based on the presence of one CF gene mutation in each chromosome (CF borderline). These patients were compared both to non-CF controls and CF patients with an abnormal sweat test (CF controls).Basal NPD values of CF borderline patients (mean value -39±6 mV, range -29 to -52 mV; n=18) were in the pathological range of CF controls (-39±8 mV, range -28 to -57 mV; n=37), and both were statistically different from values obtained in non-CF controls (-15±4 mV, range -6 to -23 mV; n=24; p<0.0001). Mutation analysis confirmed a high frequency of the 3849+10KbC→T mutation in this group of CF borderline patients (positive in 14 out of 18 subjects), whereas other mutations, such as ∆F508, Q552X, N1303K and R1162X, were also found to be associated with this atypical CF phenotype.These results confirm the presence of pathological values of basal NPD in CF patients with borderline sweat test, and also extend this finding to subjects bearing genotypes other than the G551S and 3849+10KbC→T mutations. The present findings, therefore, confirm the usefulness of measurement of basal nasal potential difference in all those patients in whom diagnosis of cystic fibrosis can be suspected but the sweat test remains inconclusive.

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“…Nasal potential difference measurement is also used as a diagnostic procedure in the evaluation for CF (14,15 ). An increased nasal potential difference is strong evidence for CF, but a value within reference intervals does not exclude the diagnosis (16 ).…”

confidence: 99%

Potential Utility of Plasma Fatty Acid Analysis in the Diagnosis of Cystic Fibrosis

et al. 2007

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Background: An altered distribution of fatty acids in cells and tissues is found in patients with cystic fibrosis (CF). In this study, we assessed the potential role of plasma fatty acid analysis in the diagnosis of CF. Methods: In this 2-part study, we first used gas chromatography–mass spectrometry to analyze fatty acids in plasma from 13 CF patients and 11 controls without CF. We then used the fatty acid distribution data to identify the fatty acids or multiple fatty acid calculations most effective in identifying CF patients. Part 2 of the study was a blinded analysis of 10 CF patients and 9 controls to directly test the effectiveness of the diagnostic parameters for CF identified from the plasma fatty acid analysis. Results: In the nonblinded trial, the multiplication product of (18:2 n-6) × (22:6 n-3) (each as percentage of total plasma fatty acid) was the most effective indicator for distinguishing patients with CF from controls (P = 0.0003). In part 2 (the blinded trial), this multiplication product was also the most effective indicator for distinguishing CF patients from controls (P = 0.0008). Conclusions: The product of (18:2 n-6) × (22:6 n-3) is effective for distinguishing CF patients from persons without CF. This diagnostic marker may have value as an alternative to the sweat chloride test in selected patients being evaluated for CF.

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Clinical application of transepithelial potential difference measurements in cystic fibrosis

Cited by 35 publications

References 16 publications

High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects

High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects

Nasal potential difference in cystic fibrosis patients presenting borderline sweat test

Potential Utility of Plasma Fatty Acid Analysis in the Diagnosis of Cystic Fibrosis

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