Children's Hospital Los Angeles, University of Southern California (USC), Los Angeles, CA, USA.
Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA.
Pediatr Res. 2020 Jan;87(1):137-145. doi: 10.1038/s41390-019-0503-8. Epub 2019 Jul 25.
There is a need to prognosticate the severity of cystic fibrosis (CF) detected by newborn screening (NBS) by early assessment of CF transmembrane conductance regulator (CFTR) protein function. We introduce novel instrumentation and protocol for evaluating CFTR activity as reflected by β-adrenergically stimulated sweat secretion.
A pixilated image sensor detects sweat rates. Compounds necessary for maximum sweat gland stimulation are applied by iontophoresis, replacing ID injections. Results are compared to a validated β-adrenergic assay that measures sweat secretion by evaporation (evaporimetry).
Ten healthy controls (HC), 6 heterozygous (carriers), 5 with CFTR-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID), and 12 CF individuals completed testing. All individuals with minimal and residual function CFTR mutations had low ratios of β-adrenergically stimulated sweat rate to cholinergically stimulated sweat rate (β/chol) as measured by either assay.
β-Adrenergic assays quantitate CFTR dysfunction in the secretory pathway of sweat glands in CF and CRMS/CFSPID populations. This novel image-sensor and iontophoresis protocol detect CFTR function with minimal and residual function and is a feasible test for young children because it is insensible to movement and it decreases the number of injections. It may also assist to distinguish between CF and CRMS/CFSPID diagnosis.
通过早期评估囊性纤维化跨膜电导调节因子（CFTR）蛋白功能，对新生儿筛查（NBS）检测到的囊性纤维化（CF）的严重程度进行预测是必要的。我们引入了一种新的仪器和方案，用于评估 CFTR 活性，其反映在β-肾上腺素能刺激的汗液分泌上。
像素图像传感器检测汗液速率。通过离子电渗法应用刺激最大汗腺所需的化合物，替代 ID 注射。结果与验证的β-肾上腺素能测定法（蒸发法）测量的汗液分泌进行比较。
10 名健康对照（HC）、6 名杂合子（携带者）、5 名 CFTR 相关代谢综合征/CF 筛查阳性、不确定诊断（CFSPID）和 12 名 CF 个体完成了测试。所有具有最小和残余 CFTR 突变功能的个体，无论使用哪种测定法，β-肾上腺素能刺激的汗液率与胆碱能刺激的汗液率（β/胆碱）的比值均较低。
β-肾上腺素能测定法定量测定 CF 和 CRMS/CFSPID 人群的汗液腺分泌途径中 CFTR 功能障碍。这种新的图像传感器和离子电渗方案可以检测最小和残余功能的 CFTR 功能，并且对于幼儿来说是可行的测试，因为它对运动不敏感，并且减少了注射次数。它还可能有助于区分 CF 和 CRMS/CFSPID 诊断。
