RT Journal Article
SR Electronic
T1 Sweat gland bioelectrics differ in cystic fibrosis: a new concept for potential diagnosis and assessment of CFTR function in cystic fibrosis
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 932
OP 938
DO 10.1136/thx.2009.115295
VO 64
IS 11
A1 T Gonska
A1 W Ip
A1 D Turner
A1 W S Han
A1 J Rose
A1 P Durie
A1 P Quinton
YR 2009
UL http://thorax.bmj.com/content/64/11/932.abstract
AB 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 β-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 hyperpolarised 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/β-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).Conclusion: 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.