Mild dehydration does not alter acute changes in sweat electrolyte concentrations during exercise.

The purpose of this study was to determine the effect of hydration status on the change in sweat sodium (Na+), chloride (Cl-), and potassium (K+) concentrations during exercise-heat stress. Fifteen subjects (Six female, nine male; 29 ± 9 y; 71 ± 14 kg) completed 90 min of cycling (81% HRmax) in the heat (~33°C, 42% rh) with fluid replacement to maintain euhydration (EUH) or without fluid to dehydrate to 2.4 ± 0.4% body mass loss (DEH). Sweat was collected from the forehead (FH), right scapula (SCAP), and left (LVFA) and right (RVFA) ventral forearms using the absorbent pad technique at the beginning (0-30 min) and end of exercise (60-90 min). Sweat was analyzed for Na+, Cl-, and K+ concentrations using ion chromatography. Data are reported as mean ± SD or median ± IQR. There were no differences (Paired t-tests or Wilcoxon signed-rank tests) between EUH and DEH in the change in sweat Na+ (FH: 24.3 ± 21.5 vs. 30.8 ± 22.4 mmol/L; SCAP: 9.7 ± 6.2 vs. 9.6 ± 8.2 mmol/L; LVFA: 7.5 ± 6.0 vs. 5.6 ± 5.9 mmol/L; RVFA: 8.2 ± 8.6 vs. 7.8 ± 5.2 mmol/L), sweat Cl-, or sweat K+ at any site (p = 0.07-0.99). The change in sweat electrolyte concentrations during 90 min of exercise in the heat was not significantly influenced by mild dehydration in recreational to moderately-trained male and female athletes.

A Double-Layer Polyurethane Electrospun Membrane with Directional Sweat Transport Ability for Use as a Soft Strain Sensor.

Wearable electronics for long-term monitoring of physiological signals should be capable of removing sweat generated during daily motion, which significantly impacts signal stability, human comfort, and safety of the electronics. In this study, we developed a double-layer polyurethane (PU) membrane with sweat-directional transport ability that can be applied for monitoring strain signals. The PU membrane was composed of a hydrophilic, conductive layer and a relatively hydrophobic layer. The double-layer PU composite membrane exhibited varied pore size and opposite hydrophilicity on its two sides, enabling the spontaneous pumping of sweat from the hydrophobic side to the hydrophilic side, i.e., the directional transport of sweat. The membrane can be used as a strain sensor to monitor motion strain over a broad working range of 0% to 250% with high sensitivity (GF = 4.11). The sensor can also detect simple human movements even under sweating conditions. We believe that the strategy demonstrated here will provide new insights into the design of next-generation strain sensors.

A skin-interfaced microfluidic platform supports dynamic sweat biochemical analysis during human exercise.

Blood lactate concentration is an established circulating biomarker for measuring muscle acidity and can be evaluated for monitoring endurance, training routines, or athletic performance. Sweat is an alternative biofluid that may serve similar purposes and offers the advantage of noninvasive collection and continuous monitoring. The relationship between blood lactate and dynamic sweat biochemistry for wearable engineering applications in physiological fitness remains poorly defined. Here, we developed a microfluidic wearable band with an integrated colorimetric timer and biochemical assays that temporally captures sweat and measures pH and lactate concentration. A colorimetric silver nanoplasmonic assay was used to measure the concentration of lactate, and dye-conjugated SiO2 nanoparticle-agarose composite materials supported dynamic pH analysis. We evaluated these sweat biomarkers in relation to blood lactate in human participant studies during cycling exercise of varying intensity. Iontophoresis-generated sweat pH from regions of actively working muscles decreased with increasing heart rate during exercise and was negatively correlated with blood lactate concentration. In contrast, sweat pH from nonworking muscles did not correlate with blood lactate concentration. Changes in sweat pH and blood lactate were observed in participants who did not regularly exercise but not in individuals who regularly exercised, suggesting a relationship to physical fitness and supporting further development for noninvasive, biochemical fitness evaluations.

Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001).

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I-II (mean age: 63.5 years, interquartile range: 58.0-72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland-Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391-0.815) was achieved in 32/50 cases. The difference between sLT and VT was -4.9 ± 15.0 W. No comparative error was noted in the Bland-Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

Association between biomarkers of tobacco smoke exposure and clinical efficacy of ivacaftor in the G551D observational trial (GOAL).

BACKGROUND: Acrolein, an aldehyde in smoke from tobacco products, inhibits CFTR function in vitro. Ivacaftor is an FDA-approved potentiator that improves mutant CFTR function. This human clinical study investigated the relationship between two urinary markers of tobacco smoke exposure - the acrolein metabolite 3-HPMA and the nicotine metabolite NNAL - and sweat chloride response to ivacaftor in the G551D Observational Trial (GOAL). METHODS: 3-HPMA (low: <50th centile; moderate: 50-75th centile; high: >75th centile) and NNAL (detectable/undetectable) in GOAL samples was quantified with LC-MS/MS. Self-report of tobacco smoke exposure (Y/N) served as a subjective measure. Change in sweat chloride from pre- to 6 months post-ivacaftor treatment (ΔSC) was the primary CFTR-dependent readout. RESULTS: The sample included 151 individuals, mean age 20.7 (SD 11.4) years, range 6-59 years. Smoke exposure prevalence was 15 % per self-reports but 27 % based on detectable NNAL. 3-HPMA was increased in those reporting tobacco smoke exposure (607 vs 354 ng/ml, p = 0.008), with a higher proportion of smoke-exposed in the high- vs low-acrolein group (31 % vs 9 %, p=0.040). Compared to low-acrolein counterparts, high-acrolein participants experienced less decrease in sweat chloride (-35.2 vs -48.2 mmol/L; p = 0.020) and had higher sweat chloride values (50.6 vs 37.6 mmol/L; p = 0.020) 6 months post-ivacaftor. The odds of ivacaftor-mediated potentiation to near normative CFTR function (defined as SC6mo <40 mmol/L) was more than twice as high in the low-acrolein cohort (OR: 2.51, p = 0.026). CONCLUSIONS: Increased urinary 3-HPMA, an acrolein metabolite of tobacco smoke, is associated with a diminished sweat chloride response to ivacaftor potentiation of CFTR function.

Bioinspired Multilayered Knitted Fabric with Directional Water Transport and Collection for Personal Sweat Management.

Effective sweat management fabric for sportswear facilitates sweat removal from the skin and elevates the comfort for human. However, when the body is in a strong hot and humid environment or after strenuous exercise, the sweat management fabric will be totally wetted and saturated quickly. As a result, excess sweat cannot be absorbed effectively by the garment, which creates obvious stickiness and heaviness. In this paper, a directional water transport and collection multilayered knitted fabric (DWTCF) is prepared by plasma pretreatment technology and screen coating. The treelike water transport network inspired from nature is designed in order to drive the liquid flow along the channels. By surface modification, branched hydrophilic flow paths are fabricated, and other regions are hydrophobic. As a demonstration, DWTCF has been injected with water to observe the liquid transport behavior. During the experiment, 76.7% liquid is collected by DWTCF, but there is just 0.06% collected by an ordinary knitted fabric. The weight increase of the ordinary fabric is 555.4% larger than that of DWTCF. Specifically, DWTCF utilizes the wetting and pressure-gradient-induced interfacial tension as well as the gravitational effect to facilitate the fluid motion along the hydrophilic channel, in addition to the capillarity present in the fabric structure. This study provides a new idea to develop directional water transport and collection fabric to solve the moisture absorption saturation problem of the fabric, especially for conditions requiring intense sweating.

A Wearable Thin-Film Hydrogel Laser for Functional Sensing on Skin.

Flexible photonics offers the possibility of realizing wearable sensors by bridging the advantages of flexible materials and photonic sensing elements. Recently, optical resonators have emerged as a tool to improve their oversensitivity by integrating with flexible photonic sensors. However, direct monitoring of multiple psychological information on human skin remains challenging due to the subtle biological signals and complex tissue interface. To tackle the current challenges, here, we developed a functional thin film laser formed by encapsulating liquid crystal droplet lasers in a flexible hydrogel for monitoring metabolites in human sweat (lactate, glucose, and urea). The three-dimensional cross-linked hydrophilic polymer serves as the adhesive layer to allow small molecules to penetrate from human tissue to generate strong light--matter interactions on the interface of whispering gallery modes resonators. Both the hydrogel and cholesteric liquid crystal microdroplets were modified specifically to achieve high sensitivity and selectivity. As a proof of concept, wavelength-multiplexed sensing and a prototype were demonstrated on human skin to detect human metabolites from perspiration. These results present a significant advance in the fabrication and potential guidance for wearable and functional microlasers in healthcare.

Anti-inflammatory effects of elexacaftor/tezacaftor/ivacaftor in adults with cystic fibrosis heterozygous for F508del.

Inflammation is a key driver in the pathogenesis of cystic fibrosis (CF). We assessed the effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on downregulating systemic and immune cell-derived inflammatory cytokines. We also monitored the impact of ETI therapy on clinical outcome. Adults with CF, heterozygous for F508del (n = 19), were assessed at baseline, one month and three months following ETI therapy, and clinical outcomes were measured, including sweat chloride, lung function, weight, neutrophil count and C-reactive protein (CRP). Cytokine quantifications were measured in serum and following stimulation of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) and adenosine triphosphate and analysed using LEGEND plex™ Human Inflammation Panel 1 by flow cytometry (n = 19). ASC specks were measured in serum and caspase-1 activity and mRNA levels determined from stimulated PBMCs were determined. Patients remained stable over the study period. ETI therapy resulted in decreased sweat chloride concentrations (p < 0.0001), CRP (p = 0.0112) and neutrophil count (p = 0.0216) and increased percent predicted forced expiratory volume (ppFEV1) (p = 0.0399) from baseline to three months, alongside a trend increase in weight. Three months of ETI significantly decreased IL-18 (p< 0.0011, p < 0.0001), IL-1ß (p<0.0013, p = 0.0476), IL-6 (p = 0.0109, p = 0.0216) and TNF (p = 0.0028, p = 0.0033) levels in CF serum and following PBMCs stimulation respectively. The corresponding mRNA levels were also found to be reduced in stimulated PBMCs, as well as reduced ASC specks and caspase-1 levels, indicative of NLRP3-mediated production of pro-inflammatory cytokines, IL-1ß and IL-18. While ETI therapy is highly effective at reducing sweat chloride and improving lung function, it also displays potent anti-inflammatory properties, which are likely to contribute to improved long-term clinical outcomes.

No effect of tattoos on local sweat concentrations of select cytokines, cortisol, glucose, blood urea nitrogen, or lactate during exercise.

Due to growing interest in the investigation of exercise induced sweat biomarkers to assess an individual's health and the increasing prevalence of tattoos in the world's population, investigators sought to determine whether local sweat concentrations and excretion rates of epidermal growth factor (EGF), interleukin (IL) -1α, IL-6, IL-8, cortisol, glucose, blood urea nitrogen (BUN), and lactate differ between tattooed and contralateral non-tattooed skin during exercise. Sixteen recreational exercisers [female (50%)] (age = 25-48 years) with ≥ 1 unilateral permanent tattoo [median tattoo age = 6 years, IQR = 5] on the arm/torso completed an outdoor group fitness session. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate concentrations. There were no significant differences between tattooed and non-tattooed skin for sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, or lactate excretion rate. Findings suggest that permanent tattoos older than 1 year may not impact local sweat EGF, IL-1α, IL-8, cortisol, glucose, BUN, and lactate concentrations or excretion rates during exercise.Clinical trial identifier NCT04920266 was registered on June 9, 2021.

Reliability and validity of the MX3 portable sweat sodium analyser during exercise in warm conditions.

PURPOSE: Accurately measuring sweat sodium concentration ([Na+]) in the field is advantageous for coaches, scientists, and dieticians looking to tailor hydration strategies. The MX3 hydration testing system is a new portable analyser that uses pre-calibrated biosensors to measure sweat [Na+]. This study aimed to assess the validity and reliability of the MX3 hydration testing system. METHODS: Thirty-one (11 females) recreationally active participants completed one experimental trial. During this trial, participants exercised at a self-selected pace for 45 min in a warm environment (31.5 ± 0.8 °C, 63.2 ± 1.3% relative humidity). Sweat samples were collected from three measurement sites using absorbent patches. The samples were then analysed for sweat [Na+] using both the MX3 hydration testing system and the Horiba LAQUAtwin-NA-11. The reliability of the MX3 hydration testing system was determined following two measurements of the same sweat sample. RESULTS: The mean difference between measurements was 0.1 mmoL·L-1 (95% limits of agreement (LoA): - 9.2, 9.4). The analyser demonstrated a coefficient of variation (CV) of 5.6% and the standard error of measurement was 3.3 mmoL·L-1. When compared to the Horiba LAQUAtwin-NA-11, there was a mean difference of - 1.7 mmoL·L-1 (95% LoA: - 0.25 X ¯ , 0.25 X ¯ ) and the CV was 9.8%. CONCLUSION: The MX3 hydration testing system demonstrated very good single-trial reliability, moderate agreement and a very good CV relative to the Horiba LAQUAtwin-Na-11. To further validate its performance, the MX3 hydration testing system should be compared with analytical techniques known for superior reliability and validity.

Heterogeneity of CFTR modulator-induced sweat chloride concentrations in people with cystic fibrosis.

BACKGROUND: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator. METHODS: PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies. RESULTS: Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %). CONCLUSIONS: Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population.

Ultra-Sensitive and Stable Multiplexed Biosensors Array in Fully Printed and Integrated Platforms for Reliable Perspiration Analysis.

Electrochemical biosensors have emerged as one of the promising tools for tracking human body physiological dynamics via non-invasive perspiration analysis. However, it remains a key challenge to integrate multiplexed sensors in a highly controllable and reproducible manner to achieve long-term reliable biosensing, especially on flexible platforms. Herein, a fully inkjet printed and integrated multiplexed biosensing patch with remarkably high stability and sensitivity is reported for the first time. These desirable characteristics are enabled by the unique interpenetrating interface design and precise control over active materials mass loading, owing to the optimized ink formulations and droplet-assisted printing processes. The sensors deliver sensitivities of 313.28 µA mm-1 cm-2 for glucose and 0.87 µA mm-1 cm-2 for alcohol sensing with minimal drift over 30 h, which are among the best in the literature. The integrated patch can be used for reliable and wireless diet monitoring or medical intervention via epidermal analysis and would inspire the advances of wearable devices for intelligent healthcare applications.

Monitoring of Sweat Ions and Physiological Parameters via a Reconfigurable Modular System.

In recent years, wearable sensors have revolutionized health monitoring by enabling continuous, real-time tracking of human health and performance. These noninvasive devices are usually designed to monitor human physical state and biochemical markers. However, enhancing their functionalities often demands intricate customization by designers and additional expenses for users. Here, we present a strategy using assembled modular circuits to customize health monitoring wearables. The modular circuits can be effortlessly reconfigured to meet various specific requirements, facilitating the incorporation of diverse functions at a lower cost. To validate this approach, modular circuits were employed to develop four distinct systems for in vitro evaluations. These systems enabled the detection of sweat biomarkers and physical signals under various scenarios, including sedentary state, exercise, and daily activities with or without incorporating iontophoresis to induce sweat. Four key sweat markers (K+, Ca2+, Na+, and pH) and three essential physical indicators (heart rate, blood oxygen levels, and skin temperature) are selected as the detection targets. Commercial methods were also used to evaluate the potential for effective health monitoring with our technique. This reconfigurable modular wearable (ReModuWear) system promises to provide more easy-to-use and comprehensive health assessments. Additionally, it may contribute to environmental sustainability by reusing modules.

Enrichment of sweat-derived extracellular vesicles of human and bacterial origin for biomarker identification.

Sweat contains biomarkers for real-time non-invasive health monitoring, but only a few relevant analytes are currently used in clinical practice. In the present study, we investigated whether sweat-derived extracellular vesicles (EVs) can be used as a source of potential protein biomarkers of human and bacterial origin. Methods: By using ExoView platform, electron microscopy, nanoparticle tracking analysis and Western blotting we characterized EVs in the sweat of eight volunteers performing rigorous exercise. We compared the presence of EV markers as well as general protein composition of total sweat, EV-enriched sweat and sweat samples collected in alginate skin patches. Results: We identified 1209 unique human proteins in EV-enriched sweat, of which approximately 20% were present in every individual sample investigated. Sweat derived EVs shared 846 human proteins (70%) with total sweat, while 368 proteins (30%) were captured by medical grade alginate skin patch and such EVs contained the typical exosome marker CD63. The majority of identified proteins are known to be carried by EVs found in other biofluids, mostly urine. Besides human proteins, EV-enriched sweat samples contained 1594 proteins of bacterial origin. Bacterial protein profiles in EV-enriched sweat were characterized by high interindividual variability, that reflected differences in total sweat composition. Alginate-based sweat patch accumulated only 5% proteins of bacterial origin. Conclusion: We showed that sweat-derived EVs provide a rich source of potential biomarkers of human and bacterial origin. Use of commercially available alginate skin patches selectively enrich for human derived material with very little microbial material collected.

A fluorescence imaging technique suggests that sweat leakage in the epidermis contributes to the pathomechanism of palmoplantar pustulosis.

Sweat is an essential protection system for the body, but its failure can result in pathologic conditions, including several skin diseases, such as palmoplantar pustulosis (PPP). As reduced intraepidermal E-cadherin expression in skin lesions was confirmed in PPP skin lesions, a role for interleukin (IL)-1-rich sweat in PPP has been proposed, and IL-1 has been implicated in the altered E-cadherin expression observed in both cultured keratinocytes and mice epidermis. For further investigation, live imaging of sweat perspiration on a mouse toe-pad under two-photon excitation microscopy was performed using a novel fluorescent dye cocktail (which we named JSAC). Finally, intraepidermal vesicle formation which is the main cause of PPP pathogenesis was successfully induced using our "LASER-snipe" technique with JSAC. "LASER-snipe" is a type of laser ablation technique that uses two-photon absorption of fluorescent material to destroy a few acrosyringium cells at a pinpoint location in three-dimensional space of living tissue to cause eccrine sweat leakage. These observatory techniques and this mouse model may be useful not only in live imaging for physiological phenomena in vivo such as PPP pathomechanism investigation, but also for the field of functional physiological morphology.

Metabolite monitoring concept for the biometric identification of individuals from the skin surface.

This study aims at proof of concept that constant monitoring of the concentrations of metabolites in three individuals' sweat over time can differentiate one from another at any given time, providing investigators and analysts with increased ability and means to individualize this bountiful biological sample. A technique was developed to collect and extract authentic sweat samples from three female volunteers for the analysis of lactate, urea, and L-alanine levels. These samples were collected 21 times over a 40-day period and quantified using a series of bioaffinity-based enzymatic assays with UV-vis spectrophotometric detection. Sweat samples were simultaneously dried, derivatized, and analyzed by a GC-MS technique for comparison. Both UV-vis and GC-MS analysis methods provided a statistically significant MANOVA result, demonstrating that the sum of the three metabolites could differentiate each individual at any given day of the time interval. Expanding upon previous studies, this experiment aims to establish a method of metabolite monitoring as opposed to single-point analyses for application to biometric identification from the skin surface.

Passive sweat wearable: A new paradigm in the wearable landscape toward enabling "detect to treat" opportunities.

Growing interest over recent years in personalized health monitoring coupled with the skyrocketing popularity of wearable smart devices has led to the increased relevance of wearable sweat-based sensors for biomarker detection. From optimizing workouts to risk management of cardiovascular diseases and monitoring prediabetes, the ability of sweat sensors to continuously and noninvasively measure biomarkers in real-time has a wide range of applications. Conventional sweat sensors utilize external stimulation of sweat glands to obtain samples, however; this stimulation influences the expression profile of the biomarkers and reduces the accuracy of the detection method. To address this limitation, our laboratory pioneered the development of the passive sweat sensor subfield, which allowed for our progress in developing a sweat chemistry panel. Passive sweat sensors utilize nanoporous structures to confine and detect biomarkers in ultra-low sweat volumes. The ability of passive sweat sensors to use smaller samples than conventional sensors enable users with sedentary lifestyles who perspire less to benefit from sweat sensor technology not previously afforded to them. Herein, the mechanisms and strategies of current sweat sensors are summarized with an emphasis on the emerging subfield of passive sweat-based diagnostics. Prospects for this technology include discovering new biomarkers expressed in sweat and expanding the list of relevant detectable biomarkers. Moreover, the accuracy of biomarker detection can be enhanced with machine learning using prediction algorithms trained on clinical data. Applying this machine learning in conjunction with multiplex biomarker detection will allow for a more holistic approach to trend predictions. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

3D-printed epidermal sweat microfluidic systems with integrated microcuvettes for precise spectroscopic and fluorometric biochemical assays.

Systems for capture, storage and analysis of eccrine sweat can provide insights into physiological health status, quantify losses of water, electrolytes, amino acids and/or other essential species, and identify exposures to adverse environmental species or illicit drugs. Recent advances in materials and device designs serve as the basis for skin-compatible classes of microfluidic platforms and in situ colorimetric assays for precise assessments of sweat rate, sweat loss and concentrations of wide-ranging types of biomarkers in sweat. This paper presents a set of findings that enhances the performance of these systems through the use of microfluidic networks, integrated valves and microscale optical cuvettes formed by three dimensional printing in hard/soft hybrid materials systems, for accurate spectroscopic and fluorometric assays. Field studies demonstrate the capability of these microcuvette systems to evaluate the concentrations of copper, chloride, and glucose in sweat, along with the pH of sweat, with laboratory-grade accuracy and sensitivity.

Diverse Drug Classes Partition into Human Sweat: Implications for Both Sweat Fundamentals and for Therapeutic Drug Monitoring.

ABSTRACT: Therapeutic drug monitoring to optimize drug therapy typically relies on the inconvenience of repeated plasma sampling. Sweat is a potential alternative biofluid convenient for sampling. However, limited information exists regarding the range of drugs excreted in sweat and their correlation with plasma concentrations. This study evaluated drugs in sweat and plasma of an ambulatory clinical cohort. Pilocarpine-induced sweat was collected from ambulatory participants at a single instance using an absorbent nylon mesh, followed by concurrent blood sampling for ratio and correlation analyses. In a model drug study, the pharmacokinetics of acetaminophen in sweat and plasma were compared. Of the 14 drugs and 2 metabolites monitored in the clinical study, all compounds were present in sweat and plasma; however, the sweat-to-plasma ratio varied substantially across the drugs. Opioids and methocarbamol demonstrated the highest concentrations in sweat, sometimes exceeding plasma concentrations. Selected antidepressants and muscle relaxants were also detected in sweat at a 2-10-fold dilution to the plasma. Others, such as gabapentin and pregabalin, were highly diluted (>30-fold) in sweat compared with plasma. Together, these data suggest that molecular attributes, specifically hydrophobicity (logP) and charge state at physiologic pH (7.4), enable reasonable prediction of sweat-to-plasma drug correlation. These findings demonstrated that sweat could be used as an alternative biofluid for therapeutic drug monitoring. The findings also suggest that although it has been broadly accepted that small hydrophobic molecules most likely have a strong plasma correlation, there is a small window of hydrophobicity and charge state that permits sweat partitioning.

Inhibiting regional sweat evaporation modifies the ventilatory response to exercise: interactions between core and skin temperature.

In humans, elevated body temperatures can markedly increase the ventilatory response to exercise. However, the impact of changing the effective body surface area (BSA) for sweat evaporation (BSAeff) on such responses is unclear. Ten healthy adults (9 males, 1 female) performed eight exercise trials cycling at 6 W/kg of metabolic heat production for 60 min. Four conditions were used where BSAeff corresponded to 100%, 80%, 60%, and 40% of BSA using vapor-impermeable material. Four trials (one at each BSAeff) were performed at 25°C air temperature, and four trials (one at each BSAeff) at 40°C air temperature, each with 20% humidity. The slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) assessed the ventilatory response. At 25°C, the V̇E/V̇co2 slope was elevated by 1.9 and 2.6 units when decreasing BSAeff from 100 to 80 and to 40% (P = 0.033 and 0.004, respectively). At 40°C, V̇E/V̇co2 slope was elevated by 3.3 and 4.7 units, when decreasing BSAeff from 100 to 60 and to 40% (P = 0.016 and P < 0.001, respectively). Linear regression analyses using group average data from each condition demonstrated that end-exercise mean body temperature (integration of core and mean skin temperature) was better associated with the end-exercise ventilatory response, compared with core temperature alone. Overall, we show that impeding regional sweat evaporation increases the ventilatory response to exercise in temperate and hot environmental conditions, and the effect is mediated primarily by increases in mean body temperature.NEW & NOTEWORTHY Exercise in the heat increases the slope of the relation between minute ventilation and carbon dioxide elimination (V̇E/V̇co2 slope) in young healthy adults. An indispensable role for skin temperature in modulating the ventilatory response to exercise is noted, contradicting common belief that internal/core temperature acts independently as a controller of ventilation during hyperthermia.