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Sweat Gland Bioelectrics Differ In Cystic Fibrosis: A New Concept For Potential Diagnosis And Assessment Of Cftr Function In Cystic Fibrosis
  1. Tanja Gonska (tanjagonska{at}gmail.com)
  1. University of Toronto, Canada
    1. Wan Ip (wan.ip{at}sickkids.ca)
    1. Hospital for Sick Children, Canada
      1. Dan Turner
      1. The Hebrew University, Israel
        1. WonSun Han (sunny.han{at}yale.edu)
        1. University of California, San Diego, United States
          1. Jennifer Rose
          1. Hospital for Sick Children, Canada
            1. Peter Durie (peter.durie{at}sickkids.on.ca)
            1. University of Toronto, Canada
              1. Paul M. Quinton (pquinton{at}ucsd.edu)
              1. University of California, San Diego and University of California, Riverside, United States

                Abstract

                Background: For nearly 50 years, the diagnosis of Cystic Fibrosis (CF) has depended on measurements of sweat Cl- concentration. While the validity of this test is universally accepted, increasing diagnostic challenges and the search for adequate biomarker assays to support curative oriented clinical drug trials have created a new demand for accurate, reliable and more practical CF tests. Herein, we propose a novel concept that may provide a more efficient, real time method to assess CFTR function in vivo.

                Methods: Cholinergic and β-adrenergic agonists were iontophoresed to stimulate sweating. The electrical potential from stimulated sweat glands (SPD) was measured in vivo using a standard electrocardiogram (ECG) electrode applied to the skin surface. SPD and sweat chloride concentrations were compared in cohorts predicted to express a range of CFTR function as presented by healthy controls (HC), heterozygotes (Hz), pancreatic sufficient (CFPS) and pancreatic insufficient CF patients (CFPI).

                Results: The median SPD was hyperpolarized in CF compared to control subjects (-47.4 mV vs. -14.5 mV, p<0.0001). In distinguishing between control and CF subjects, SPD (Area under Receiver-Operator Curve, AUC = 0.997) was similar to sweat [Cl-] (AUC = 0.986). Sequential cholinergic/β-adrenergic sweat stimulation dramatically depolarized the SPD in CF (p<0.001), but had no effect in control subjects (p=0.6) or on sweat [Cl-] in either group (p>0.5). Further, the positive SPD response was larger in CFPI than in CFPS subjects (p=0.04).

                Interpretation: These results support the concept that skin surface voltages arising from stimulated sweat glands can be exploited to assess expressed CFTR function in vivo and may prove to be a useful diagnostic tool.

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