CFTR modulation with elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis assessed by the β-adrenergic sweat rate assay

How the sweat gland reveals levels of CFTR activity

“…The present analysis, which is expanded in Section 7 , does not require different modulator effects on CFTR in coil and duct. However, β-sweat rates can underestimate CFTR activity even after correction for losses [7] , and there is full agreement between the authors' conclusion [42] and the conclusion of this review that sweat chloride measurements are at present the most sensitive way to monitor modulator effects.…”

“…Sweat chloride and β-sweat rates of patients taking elexacaftor/tezacaftor/ivacaftor were directly compared in a recent study using improved methodology to measure β-sweating much more efficiently [42] . For 22 CF patients with at least one F508del allele (10 were homozygous) who were taking the triple combo and were tested for both sweat chloride and β-sweating, mean sweat chloride was 44.6 ± 17.1 mmol/L, and their mean β/M ratio was 7% of the mean β/M ratio in 11 healthy control subjects.…”

“…For 22 CF patients with at least one F508del allele (10 were homozygous) who were taking the triple combo and were tested for both sweat chloride and β-sweating, mean sweat chloride was 44.6 ± 17.1 mmol/L, and their mean β/M ratio was 7% of the mean β/M ratio in 11 healthy control subjects. (Based on data from on Supplementary Tables 1 and 2 in ref [42] ). Little correlation was seen between the two measures for individual patients.…”

“…5 ). The authors suggest that the large effects on sweat chloride and small effects on β-sweating might arise because CFTR in the coil has a more stringent requirements for a wild type CFTR conformation, whereas the duct tolerates residual defects in CFTR [42] . The present analysis, which is expanded in Section 7 , does not require different modulator effects on CFTR in coil and duct.…”

β‐adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?

“…Other studies with adult subjects employing bubble imaging‐based ratiometric sweat rate assays after β‐adrenergic stimulation report similar accuracy in distinguishing CF, CFTR heterozygotes and healthy controls with β‐adrenergic:cholinergic ratio cut‐off values of 0.0055 or less 8,9 . Sweat bubble imaging techniques are technically difficult to operate but are more sensitive than evaporimetry at detecting small but physiologically important differences that distinguish CF from CFTR‐RD or measuring the effects of CFTR‐modulating drugs on CFTR activity 8,10,13,20 . In our study the clinical objective was to exclude CF or CFTR‐RD in people presenting with clinically suspected CF for which evaporimetry performed well with optimal cut‐off values in adults of Δβ‐adrenergic 4.5 TEWL and β‐adrenergic:cholinergic ratio 0.05.…”