The Verona center has recently published data confirming the approximately linear readout of CFTR function obtained in bubble tests performed in three groups (CF subjects, CF carriers and non-CF controls, n = 22 in each group). Results showed that all groups were clearly discriminated, with sensibility and specificity ranging from 82% to 100%. The Verona group recently reported data on a new Optical Sweat Rate Beta Adrenergic (OSRBA) test for measuring sweat rates in individual human sweat glands based on a multilinear regression model. It showed that the volume of sweat secretory glands discriminated between CFTR genotypes and allowed quantifying the efficacy of pharmacological treatments with CFTR modulators; i.e. lumacaftor/ivacaftor (Orkambi) or PTC 124 (Ataluren). The increased sensitivity of bubble imaging may be required to detect small but physiologically important increases in secretion rates produced by CFTR modulators. The Brussels center had success in the development of a non-invasive version of the test by iontophoresis of the pharmacological agents used, which is particularly challenging for those triggering the β-adrenergic phase of the test. Interim results obtained from 10 patients with CF, 29 healthy subjects and 1 CF carrier confirmed the good discriminative power of the test. In conclusion, researchers gave data during this project that, either under intradermal injections or iontophoresis, the sweat droplet (bubble) test is able to fully discriminate between CF, non-CF and healthy subjects. Further comparative studies between measurements of bubble volumes and of water evaporated during sweat are ongoing.
Pubblications
– Bergamini G, Tridello G, Calcaterra E et al “Ratiometric sweat secretion optical test in cystic fibrosis, carriers and healthy subjects” Journal of Cystic Fibrosis, 2018 Mar;17(2):186-189
Congress abstracts
– Teresinha L., Viphonephom P., Hoyep Tchanchou A. et al. “False-positive beta-sweat secretion test” The 30th Annual North American Cystic Fibrosis Conference, Orlando, Florida, October 27–29, 2016
– Calcaterra E, Tridello G, Leal T et al. “Sviluppo di un test della funzione CFTR in vivo: misurazione in ghiandole sudoripare umane mediante immagini della sudorazione dipendente dal canale difettoso in fibrosi cistica rispetto a quella indipendente” Congresso Nazionale SIFC, 9-11 Novembre 2016, Salerno
– Bergamini G, Calcaterra E, Ceri S et al “Testing CFTR function in vivo by imaged ratiometric measurement of beta-adrenergic/cholinergic sweat rate in human sweat glands” 17th Scientific Meeting “”Organoids as models for disease and treatment in CF, September 21st + 22nd 2017 Schloss Waldhausen/Mainz
– Leal T, Noel S, Bergamini G et al “Topical eye treatment with β-blocker abolishes sweat secretion triggered by intradermal isoprenaline plus aminophylline: a clinical observation” ECFS 40th European Cystic Fibrosis Conference, 7-10 Giugno 2017, Siviglia, Spagna
– Reynaerts A, Melotti P, Vermeulen F et al “Implementation d’une version non-invasive, controlee par imagerie, du test de secretion β-adrénergique de la suer: aide au diagnostic et marquer d’efficacité thérapeutique” 19e Édition du Colloques français des jeunes chercheurs en Mucoviscidose, Paris, Institut Pasteur, 20 février 2018
– Reynaerts A, Melotti P, Vermeulen F et al “Non-invasive image-controlled β-adrenergic sweat test by iontophoresis” 12th Cystic Fibrosis European Young Investigators’ Meeting (EYIM), Paris, Institut Pasteur, 21-23 February 2018
– Melotti P, Lecca P, Esposito V et al. “Measurements of beta-adrenergic vs cholinergic sweat rates in single human sweat glands” North American Cystic Fibrosis Conference (NACF), October 18-20, 2018, Denver, CO, US