Optical measurement of CFTR-dependent sweat secretion stimulated by a beta-adrenergic cocktail (C-phase) vs. CFTR-independent sweat secretion induced by methacholine (M-phase) can discriminate cystic fibrosis (CF) patientts from controls and healthy carriers by the ratio of sweat rate in the C-phase vs. the M-phase (C/M ratio). However, image analysis is experimentally demanding and time-consuming. Here, sweat droplet number (SDN) in the C-phase, corresponding to the number of sweat-secreting glands, was a statistically significant predictor for detecting the effects of CFTR-targeted therapy. We show that in 44 non-CF subjects and 110 CF patients, SDN in the C-phase provides a linear readout of CFTR function that is more sensitive than that using the C/M ratio. In CF patients, increased SDN in the C-phase during treatment with (LUMA/IVA) was associated with a trend toward improved lung function (FEV1). Our method is suitable for multicenter monitoring of the effects of CFTR modulators.

Optical Measurements of Sweat for in Vivo Quantification of CFTR Function in Individual Sweat Glands / D. Treggiari, K. Kleinfelder, M. Bertini, G. Tridello, A. Fedrigo, E. Pintani, P. Iansa, A. Casiraghi, P. Minghetti, M. Cipolli, C. Sorio, P. Melotti. - In: JOURNAL OF CYSTIC FIBROSIS. - ISSN 1569-1993. - 20:5(2021 Sep), pp. 824-827. [10.1016/j.jcf.2021.03.003]

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

A. Casiraghi;P. Minghetti;
2021

Abstract

Optical measurement of CFTR-dependent sweat secretion stimulated by a beta-adrenergic cocktail (C-phase) vs. CFTR-independent sweat secretion induced by methacholine (M-phase) can discriminate cystic fibrosis (CF) patientts from controls and healthy carriers by the ratio of sweat rate in the C-phase vs. the M-phase (C/M ratio). However, image analysis is experimentally demanding and time-consuming. Here, sweat droplet number (SDN) in the C-phase, corresponding to the number of sweat-secreting glands, was a statistically significant predictor for detecting the effects of CFTR-targeted therapy. We show that in 44 non-CF subjects and 110 CF patients, SDN in the C-phase provides a linear readout of CFTR function that is more sensitive than that using the C/M ratio. In CF patients, increased SDN in the C-phase during treatment with (LUMA/IVA) was associated with a trend toward improved lung function (FEV1). Our method is suitable for multicenter monitoring of the effects of CFTR modulators.
CFTR-targeted therapy; cystic fibrosis; image analysis; Sweat glands
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
2-apr-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/841911
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