Optical Measurements of Sweat for in Vivo Quantification of CFTR Function in Individual Sweat Glands

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

“…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 CFTRmodulating drugs on CFTR activity. 8,10,13,20 In our study observed in our cohort. [22][23][24][25] One adult male in this study with repeatedly high SCT values (90 mmol/L) was newly diagnosed with HIV-infection and had an ichthyosis-like skin disorder.…”

“…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.…”

“…The β‐adrenergic sweat secretion test was performed as described by Quinton et al (2012) by intradermal injection of atropine sulfate (0.2 ml, 44 µg/ml) below the reference probe, followed by sequential intradermal injection of carbachol (0.1 ml, 0.1 µg/ml), atropine sulfate (0.2 ml, 44 µg/ml), and finally 0.2 ml β‐adrenergic cocktail containing atropine sulfate (8.0 µg), isoproterenol (4.4 µg) and aminophylline (0.84 mg) below the measuring probe 6 . Stock solutions were prepared by a research pharmacist at least 48 h before participant testing and stored at 4°C to ensure drug stability 13 …”

“…6 Stock solutions were prepared by a research pharmacist at least 48 h before participant testing and stored at 4°C to ensure drug stability. 13 Peak/Δcholinergic, peak/Δβ-adrenergic TEWL and β-adrenergic:cholinergic ratio were recorded and calculated in each participant. A previously described "modified" BAST protocol and analysis measuring only peak/Δβ-adrenergic TEWL was applied in children <6 years age where the full protocol could not be followed, or if cholinergic secretion in response to carbachol was not detected for any reason.…”

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

“…Whereas QPIT measures the CFTR-mediated reabsorption of chloride in the sweat duct [12] , the β-adrenergic sweat secretion test (SST) measures CFTR-mediated secretion of chloride in the secretory coil of the sweat gland [13][14][15][16][17] . Sato and Sato discovered in the early 1980s that CFTR-mediated sweat secretion can be stimulated with β-adrenergic agonists if the thermoregulative cholinergic sweat secretion is simultaneously inhibited with atropine [18] .…”