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Hôpital Necker – Enfants Malades, Paris, France.
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Editor’s note: A significant number of children who have clinical features suggestive of cystic fibrosis (CF) do not meet the current diagnostic criteria for CF because their sweat chloride levels are in the intermediate range (30–60 mmol/L). Extensive genetic studies in these patients often find one (or no) mutation in the CF transmembrane conductance regulator (CFTR), or genetic variations with unclear pathogenic potential. In cases with an inconclusive diagnosis of CF, assessment of CFTR function may help uncover a definitive diagnosis. CFTR-dependent chloride secretion – which is absent in typical cases of CF but normal or present at minimally reduced levels in atypical cases (i.e. among heterozygotes) – can be indirectly assessed by measuring changes in nasal transepithelial potential difference (NPD) after the pharmacological activation of protein kinase A. This assessment can help to make a diagnosis of CF in patients with CF-like symptoms, distinguishing those with atypical CF (evidence of CFTR dysfunction) from those who are unlikely to have CF (normal CFTR function).