Beta-adrenergic sweat test in challenging cystic fibrosis diagnosis.

Cystic Fibrosis (CF) diagnosis relies on a sweat chloride concentration above 60 mmol/L or the identification of 2 CF-causing variants. However, when sweat chloride is intermediate or if only one variant is identified, diagnosis is challenging. Functional testing by nasal potential difference and intestinal current measurement in rectal biopsies is then recommended, but few centers perform these specialized tests (PMID: 37775442). The beta-adrenergic (β-adr) sweat secretion test (SST) specifically evaluates CFTR activity in the sweat gland and could be an interesting alternative as the equipment and cost is more accessible. Moreover, it is more discriminate than the standard CFTR functional explorations in distinguishing CF from non-CF patients (PMID: 35777769). 44 children and 55 adults underwent the standard sweat test, the β-adr SST and genetic studies to identify CF-causing variants and distinguish Variants of Varying Clinical Consequence (VVCC) and of Unknown Significance (VUS) which represent a diagnostic challenge. All healthy controls presented a normal β-adr SST, whereas 23% presented an intermediate sweat chloride concentration. Heterozygotes were all within normal β-adr SST values. Patients with two known CF-causing variants all presented a β-adr SST below the threshold. All patients with VVCC were in the CF range. Patients with VUS (S737F, E217G, D1445N, R600G) were in the CF range and could be reclassified as pathogenic. β-adr SST presents excellent negative and positive predictive values and was of great added value in CF diagnosis. β-adr SST could be added in CF diagnostic algorithms.