Data from: Evaporimeter and bubble-imaging measures of sweat gland secretion rates

Beta-adrenergically-stimulated sweat rates determined by evaporimetry or by sweat bubble imaging are useful for measuring CFTR function because they provide a near-linear readout across almost the full range of CFTR function. They differentiate cystic fibrosis (CF) subjects from CF carriers and carriers from controls. However, evaporimetry, unlike bubble imaging, appears to be unable to detect improved levels of CFTR function in G551D subjects taking the CFTR modulator ivacaftor. Here, we quantify the sensitivity of evaporimetry and bubble imaging methods for assessing low levels of CFTR-dependent sweat rates. To establish sensitivity, we did dose-ranging studies using intradermally injected [cAMP]i–elevating cocktails. We reduced isoproterenol/aminophylline levels while maintaining a high level of atropine to block muscarinic elevation of [Ca2+]i. We stimulated the same sets of glands for both assays and recorded responses for 20 min. In response to a 3-log dilution of the stimulating cocktail (0.1%), bubble responses were detected in 12/12 tests (100%), with 49% ± 3% of glands secreting to produce an aggregate volume of 598 nl across the 12, 20-min tests. This was ~5% of the response to full cocktail. Evaporimetry detected responses in 3/12 (25%) tests with an aggregate secretion volume of 175 nl. After stimulation with a still more dilute cocktail (0.03%), bubble imaging detected 15 ± 13% of glands secreting at a rate ~0.9% of the response to full cocktail, while zero responding was seen with evaporimetry. The bubble imaging method detected secretion down to aggregate rates of <0.2 nl/(cm2·min), or ~1/30th of the average basal transepithelial water loss (TEWL) in the test subject of 4 g/m2·hr or 6.7 nl/(cm2·min). The increased sensitivity of bubble imaging may be required to detect small but physiologically important increases in secretion rates produced by CFTR modulators.

通过蒸发测汗法（evaporimetry）或汗泡成像法（sweat bubble imaging）测定的β肾上腺素能刺激下的汗液分泌速率，可用于评估囊性纤维化跨膜传导调节因子（CFTR）功能，因其几乎可在CFTR功能的全范围内提供近线性的检测结果。该方法能够区分囊性纤维化（CF）患者、CF携带者与健康对照人群。然而，与汗泡成像法不同的是，蒸发测汗法似乎无法检测到服用CFTR调节剂伊伐卡托（ivacaftor）的G551D突变受试者体内CFTR功能的改善水平。本研究旨在量化蒸发测汗法与汗泡成像法在评估低水平CFTR依赖型汗液分泌速率时的检测灵敏度。为确定检测灵敏度，我们采用皮内注射升高细胞内环腺苷酸（[cAMP]i）的混合试剂开展剂量梯度研究。在维持高剂量阿托品以阻断毒蕈碱型受体介导的细胞内钙离子（[Ca²+]i）升高的前提下，我们降低了异丙肾上腺素与氨茶碱的给药浓度。我们对同一组汗腺同时开展两种检测，并记录时长20分钟的分泌响应。当使用3个数量级稀释的刺激混合试剂（浓度为0.1%）时，12次检测中均（100%）检测到汗泡响应，12次20分钟检测中共有49%±3%的汗腺发生分泌，总分泌体积达598纳升，约为完全浓度混合试剂刺激下响应的5%。蒸发测汗法仅在3/12次（25%）检测中捕捉到分泌响应，总分泌体积为175纳升。当使用浓度更低的混合试剂（0.03%）进行刺激时，汗泡成像法可检测到15±13%的汗腺分泌，分泌速率约为完全浓度试剂刺激下响应的0.9%，而蒸发测汗法未检测到任何分泌响应。汗泡成像法可检测到的最低总分泌速率低于0.2纳升/(平方厘米·分钟)，约为受试对象平均基础经上皮失水（transepithelial water loss, TEWL）水平的1/30——该受试对象的基础TEWL为4克/(平方米·小时)，即6.7纳升/(平方厘米·分钟)。若要检测由CFTR调节剂介导的、虽微小但具有重要生理意义的分泌速率提升，或许需要汗泡成像法这种更高灵敏度的检测手段。