Sweat gland bioelectrics differ in cystic fibrosis: a new concept for potential diagnosis and assessment of CFTR function in cystic fibrosis
- 1Department of Paediatrics, University of Toronto, Toronto, Canada
- 2Physiology and Experimental Medicine, the Research Institute and the Department of Paediatrics, Hospital for Sick Children, Toronto, Canada
- 3Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel
- 4Department of Paediatrics, University of California School of Medicine, San Diego, La Jolla, California, USA
- 5Division of Biomedical Sciences, University of California, Riverside, California, USA
- Correspondence to Dr P Quinton, Department of Paediatrics, University of California, 9500 Gilman Dr, San Diego, La Jolla, CA 92093-0830, USA; pquinton{at}ucsd.edu
- Received 16 February 2009
- Accepted 18 August 2009
- Published Online First 3 September 2009
Abstract
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.
Footnotes
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PD and PQ are joint senior authors
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Funding The study was funded by the Canadian Cystic Fibrosis Foundation as part of the BREATHE project, a Fellowship award to TG, the US Cystic Fibrosis Foundation to PQ and PD and the Nancy Olmsted Trust to PQ.
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Competing interests None.
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Ethics approval The ethical boards of the Hospital for Sick Children and St. Michael’s Hospital in Toronto, Canada, as well as Health Canada, approved the study.
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Provenance and Peer review Not commissioned; externally peer reviewed.
