Sweat gland bioelectrics differ in cystic fibrosis: a new concept for potential diagnosis and assessment of CFTR function in cystic fibrosis.
BACKGROUND
For nearly 50 years the diagnosis of cystic fibrosis (CF) has depended on measurements of sweat chloride concentration. While the validity of this test is universally accepted, increasing diagnostic challenges and the search for adequate biomarker assays to support curative-orientated clinical drug trials have created a new demand for accurate, reliable and more practical CF tests. A novel concept is proposed that may provide a more efficient real-time method for assessing CFTR function in vivo.


METHODS
Cholinergic and beta-adrenergic agonists were iontophoresed to stimulate sweating. The bioelectric potential from stimulated sweat glands (SPD) was measured in vivo using a standard 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 patients with CF (CFPI).


RESULTS
The median SPD was hyperpolarized in patients with CF compared with control subjects (-47.4 mV vs -14.5 mV, p<0.001). In distinguishing between control and CF subjects, SPD (area under receiver operator curve (AUC) = 0.997) was similar to sweat chloride concentration (AUC = 0.986). Sequential cholinergic/beta-adrenergic sweat stimulation dramatically depolarised the SPD in patients with CF (p<0.001) but had no effect in control subjects (p = 0.6) or on the sweat chloride concentration in either group (p>0.5). Furthermore, the positive SPD response was larger in CFPI than in CFPS subjects (p = 0.04).


CONCLUSIONS
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.
Gonska
T
T
Department of Paediatrics, University of Toronto, Toronto, Canada.
Ip
W
W
Turner
D
D
Han
W S
WS
Rose
J
J
Durie
P
P
Quinton
P
P
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002712:Chlorides / Q000032:analysis*; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004812:Epidemiologic Methods; D010188:Exocrine Pancreatic Insufficiency / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D007478:Iontophoresis; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D013542:Sweat / Q000737:chemistry*; D013545:Sweat Glands / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D002712:Chlorides; D018721:Muscarinic Agonists; D010862:Pilocarpine; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007545:Isoproterenol