Skin wipe test: A simple, inexpensive, and fast approach in the diagnosis of cystic fibrosis

Abstract

Objective To assess the performance of a newly developed skin wipe test (SWT) for the diagnosis of cystic fibrosis (CF). Study Design Spontaneously formed sweat from the forearm was wiped by a cotton swab moistened with 100 µL of deionized (DI) water and extracted into 400 µL of DI water (SWT). The conventional Macroduct sweat test (ST) was performed simultaneously. SWT samples of 114 CF patients, 76 healthy carriers, and 58 controls were analyzed by capillary electrophoresis with contactless conductivity detection and Cl−/K+ and (Cl− + Na+)/K+ ion ratios were evaluated. Chloride concentrations from Macroduct ST were analyzed coulometrically. Results Analysis of 248 SWT samples and simultaneous Macroduct ST samples showed comparable method performance. Two ion ratios, Cl−/K+ and (Cl− + Na+)/K+, from the SWT samples and Cl− values from the ST samples were evaluated to diagnose CF. Sensitivity of the SWT method using the Cl−/K+ ratio (cutoff value 3.9) was 93.9%, compared to 99.1% when using the (Cl− + Na+)/K+ ratio (cutoff value 5.0) and 98.3% in using Macroduct Cl− (cutoff value higher or equal to 60 mmol/L). The methods' specificities were 97.8%, 94.0%, and 100.0%, respectively. Conclusions The developed SWT method with capillary electrophoretic analysis for CF diagnosis performs comparably to the conventional Macroduct ST. The SWT method is simple, fast, inexpensive, and completely noninvasive. Use of an ion ratio in obtained SWT samples is proposed as a new diagnostic parameter that shows significant promise in CF diagnostics.

Sweat Testing and Recent Advances

“…The sweat Cl − concentrations obtained from the wearable sensor showed excellent agreement with the conventional tests with a Pearson correlation coefficient of p = 0.97. Sweat Cl − measurements for all healthy subjects were within the accepted threshold for normal (≤29 mEq/L; [16][17][18][19][20][21][22][23][24][25][26][27], and all individuals with CF were above the accepted threshold (≥60 mEq/L; 65-130), confirming CF diagnosis. The correlation coefficient between the CFQT and conventional ST was 0.98 [95% confidence interval (CI): 0.97-0.99].…”

“…The method specificities were 97.8, 94.0, and 100.0%, respectively. The authors propose the SWT as a new diagnostic technique for CF ( 20 ).…”

“…These therapies may not result in equivalent clinical improvement for all CFTR mutations, and the Cl − concentration in sweat can serve as a useful biomarker of CFTR function, in vivo , in assessing the response to modulator treatments ( 18 ). In terms of the treatment response, studies show correlations between functional classes of CFTR variants and sweat Cl − concentration ( 19 , 20 ). In clinical use, baseline and serial sweat Cl − measurements are usually used to monitor the effects of therapies targeting CFTR function in previously diagnosed CF patients ( 4 , 16 , 17 , 21 ).…”

“…Additionally, collecting a sufficient amount of sweat can be challenging in infants (13,14). For these reasons, some devices that use different, simpler methods have been developed for measuring sweat Cl − , and the safety and efficacy of these methods are reported by controlled studies (15)(16)(17)(18)(19)(20). In this study, we review the QIPT and the newer alternatives now being employed in the diagnosis of CF.…”

Year in Review 2020: Multisystemic impact of cystic fibrosis

“…Another diagnostic conundrum for clinicians is sweat chloride testing in infants, as there can be difficulties obtaining enough sweat based on the current testing modality. Durc and colleagues 8 assessed the performance of a newly developed skin wipe test (SWT) for the diagnosis of CF. This SWT is designed to be simpler, noninvasive, less expensive, not reliant on pilocarpine iontophoresis, and more likely to obtain results in very young patients compared to traditional macroduct testing.…”