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

J Cyst Fibros. 2021 Sep;20(5):824-827. doi: 10.1016/j.jcf.2021.03.003. Epub 2021 Apr 2.

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.

Keywords: CFTR-targeted therapy; Sweat glands; cystic fibrosis; image analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminophenols / therapeutic use*
  • Aminopyridines / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Drug Combinations
  • Humans
  • Optics and Photonics
  • Quinolones / therapeutic use*
  • Sweat / drug effects
  • Sweat / metabolism*
  • Sweat Glands / drug effects
  • Sweat Glands / metabolism*

Substances

  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Drug Combinations
  • Quinolones
  • lumacaftor, ivacaftor drug combination
  • Cystic Fibrosis Transmembrane Conductance Regulator