Validity of the Wescor's sweat conductivity analyzer for the assessment of sweat electrolyte concentrations

The purpose of this study was to compare the NaCl equivalent values determined by the Wescor's sweat conductivity analyzer (Sweat-Chek) with the sweat Na⁺ and Cl^– concentration values measured by conventional methods. The sweat was induced by 60-min exercise and collected by a closed-pouch collector. The NaCl equivalent values determined by the sweat conductivity analyzer (mean: 75 mmol · L^–1, range: 38 – 122, n = 72) were significantly (P < 0.05) greater than Na⁺ concentration values (mean: 7I mmol · L^–1, range: 24 – 123, n = 72) measured by flame photometry and Cl^– concentration values (mean : 61 mmol· L^–1, range: 18 – 100, n = 48) measured by coulometric titration. The differences were most accen-tuated for low concentration values. The 95% confidence-agreement intervals around the mean differences between methods were 11 mmol· L^–1 (14%) for both Na⁺ and Cl^–. The SweatChek conductivity analyzer is a portable instrument which approximates the actual Na⁺ and Cl^– concentrations in sweat but with a positive bias probably due to the other unmeasured anions present in sweat.     

The reproducibility of closed-pouch sweat collection and thermoregulatory responses to exercise–heat stress

Seven active male subjects cycled for 60 min at 29.5 (0.8)% peak work rate on three separate occasions in a hot environmental condition [36.0 (0.1)°C, 60 (1)% relative humidity] in order to determine the reproducibility of a closed-pouch sweat collection technique for sweat composition at the scapula, forearm and thigh. To confirm that sweat composition was not influenced by between-trial variations in sudomotor drive, local sweat rate, whole-body sweat rate, heart rate (HR), rectal temperature (T_re) and mean skin temperature (T_sk) responses were also measured, consequently reproducibility was also established for these variables. Sweat composition did not differ among trials, with the mean coefficients of variation (CVs) for sweat [Na⁺], [K⁺] and pH being 10.4 (7.4)%, 8.1 (6.5)% and 1.3 (1.1)%, respectively. Local sweat rates did not differ among the three trials (P>0.05) although whole-body sweat rate was reduced in the third trial (P<0.05). The mean CVs were 11.0 (7.8)% and 4.7 (1.6)% for local and whole-body sweat rates, respectively. Between-trial differences were not evident for T_re, T_sk or HR with mean CVs of 0.3 (0.2)%, 0.7 (0.6)% and 3.9 (1.7)%, respectively, although HR tended to be greater in the first trial (P=0.08). It is proposed that moderate variations in sweat composition were influenced by variations in the local sweat rate, which were induced by application of the pouch.     

Fluid and electrolyte balance in elite gaelic football players

The aim of this study was to investigate fluid and electrolyte balance in elite Gaelic Football players (n=20) during a typical training session in a warm environment (16 to 18 degrees C, 82-88% humidity). Pre-training urine samples were used to determine hydration status. Sweat sodium concentration was collected from four body site locations using absorbent patches. The mean sweat rate per hour was 1.39 l x h(-1) and mean body mass loss was 1.1%. Mean sweat sodium concentrations were 35 mmol x l(-1) (range 19-52 mmol x l(-1)). On average, players did not drink enough fluid to match their sweat rates (p<0.001) and this fluid deficit was not related to pre-training hydration status (p= 0.67). A single hydration strategy based on published guidelines may not be suitable for an entire team due to variations in individual sweat rates. Maximising player performance could be better achieved by accurate quantification of individual fluid and electrolyte losses.     

Effect of induced metabolic alkalosis on sweat composition in men

To determine whether induced metabolic alkalosis affects sweat composition, 10 males cycled for 90 min at 62.5 +/- 1.3% peak oxygen uptake, on two separate occasions. Subjects ingested either empty capsules (placebo) or capsules containing NaHCO3- (0.3 g kg-1 body mass; six equal doses) over a 2-h period, which commenced 3 h prior to exercise. Arterialized-venous blood samples were drawn prior to and after 15, 30, 60 and 90 min of exercise. Sweat was aspirated at the end of exercise from a patch located on the right scapula region. NaHCO3- ingestion elevated blood pH, [HCO3-] and serum [Na+], whereas serum [Cl-] and [K+] were reduced, both at rest and during exercise (P < 0.05). Sweat pH was greater in the NaHCO3- trial (6.24 +/- 0.18 vs. 6.38 +/- 0.18; P < 0.05), whereas sweat [Na+] (49.5 +/- 4.8 vs. 50.2 +/- 4.3 mEq L-1), [Cl-] (37.5 +/- 5.1 vs. 39.3 +/- 4.2 mEq L-1) and [K+] (4.66 +/- 0.19 vs. 4.64 +/- 0.34 mEq L-1) did not differ between trials (P > 0.05). Sweat [HCO3-] (2.49 +/- 0.58 vs. 3.73 +/- 1.10 mEq L-1) and [lactate] (8.92 +/- 0.79 vs. 10.51 +/- 0.32 mmol L-1) tended to be greater after NaHCO3- ingestion, although significance was not reached (P=0.07 and P=0.08, respectively). These data indicate that induced metabolic alkalosis can modify sweat composition, although it is unclear whether the secretory coil, reabsorptive duct, or both are responsible for this alteration.     

Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers

Following cystic fibrosis (CF) neonatal screening implementation, a high frequency of heterozygotes has been reported among neonates with elevated immunoreactive trypsinogen (IRT) and normal sweat chloride levels. We studied the relationship between normal IRT values and CF heterozygosity: 10,000 neonates were screened for CF by IRT measurement and tested for 40 CF mutations; the 294 carriers detected were coupled with newborns negative to the same genetic testing, and the two groups' IRT levels compared. Heterozygotes had higher IRT levels than their controls (mean 35.32 vs. 27.58 microg/L, P<0.001). Even within normal trypsinogen range, the probability of being a CF carrier increases with neonatal IRT concentration.     

Acute effects of dehydration on sweat composition in men during prolonged exercise in the heat

AIM: To determine whether acute exercise-heat-induced dehydration affects sweat composition, eight males cycled for 2 h at 39.5 +/- 1.6% VO2peak on two separate occasions in a hot-humid environment (38.0 +/- 0.0 degrees C, 60.0 +/- 0.1% relative humidity). METHODS: During exercise, subjects ingested either no fluid (dehydration) or a 20 mmol L(-1) sodium chloride solution (euhydration). The volume of solution, calculated from whole-body sweat loss and determined in a familiarization trial, was ingested at 0 min and every 15 min thereafter. Venous blood was collected at 0, 60 and 120 min of exercise and sweat was aspirated from a patch located on the dominant forearm at 120 min. RESULTS: Following the 2-h cycling exercise, sweat [Na+] and [Cl-] was greater (P < 0.05) in the dehydration trial (Na+ 91.1 +/- 6.8 mmol L(-1); Cl- 73.3 +/- 3.5 mmol L(-1)) compared with the euhydration trial (Na+ 81.1 +/- 5.9 mmol L(-1); Cl- 68.5 +/- 3.3 mmol L(-1)). In addition, dehydration invoked a greater serum [Na+] (142.2 +/- 0.7 mmol L(-1); P < 0.05), [Cl-] (105.8 +/- 0.6 mmol L(-1); P < 0.05) and [K+] (5.27 +/- 0.2 mmol L(-1); P < 0.05) over the euhydration values for [Na+], [Cl-] and [K+], respectively (138.9 +/- 0.6, 102.9 +/- 0.5 and 4.88 +/- 0.1 mmol L(-1)). Plasma aldosterone was also significantly higher during exercise in the dehydration trial compared with the euhydration trial (53.8 +/- 3.8 vs. 40.0 +/- 4.3 ng dL(-1); P < 0.05). CONCLUSIONS: Acute exercise-heat stress without fluid replacement resulted in a greater sweat [Na+] and [Cl-] which was potentially related to greater extracellular fluid [Na+], plasma aldosterone or sympathetic nervous activity.     

Validity and reliability of the Horiba C-122 compact sodium analyzer in sweat samples of athletes

Accurate sodium replacement during prolonged exercise is possible when sweat rate and sweat sodium content are directly measured. Few athletes have access to sweat sodium content measurement, as the equipment needed to perform such analyzes is costly, laboratory-based or requires technical skills. Using 70 sweat samples collected in 24 athletes from 3 anatomical sites, this study determined the reliability [single-trial and inter-day (7 samples over 3?days)] and validity (instrument error) of a pocket-sized, easy-to-use and low cost sodium analyzer (Horiba C-122, Kyoto, Japan) against reference values of an ion chromatograph, the 883 Basic IC plus (Metrohm AG, Herisau, Switzerland). The Horiba C-122 showed high single-trial reliability with an intraclass correlation coefficient (ICC) of 0.997, a typical error of measurement (EM) of 1.77?mmol/L and a coefficient of variation (CV) of 3.73%. As expected, the reliability of the 883 Basic IC plus was superior to that of the Horiba C-122 (ICC: 0.999; typical EM: 0.70?mmol/L; CV: 1.52%). The Horiba’s C-122 inter-day reliability was high (ICC: 1.00; typical EM: 0.35?mmol/L). An ICC of 0.975 indicates there was a strong relationship between results provided by both analyzers. Compared with reference values, the Horiba C-122 demonstrated a mean bias of 1.71?mmol/L, a pure EM of 7.52?mmol/L and 68% limits of agreement ranging from ?5.81 to 9.23?mmol/L. We propose that the Horiba C-122 is sufficiently reliable to be used under field conditions where some degree of imprecision is acceptable, but not for research purposes where high accuracy is required.     

Functional interaction of CFTR and ENaC in sweat glands

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a significant role in transepithelial salt absorption as well as secretion by a number of epithelial tissues including sweat glands, airways and intestine. Early studies suggested that in absorption significant cross talk occurs between CFTR Cl(-) channels and epithelial Na(+) channels (ENaC). Studies based primarily on cultured cells of the airways and on ex vivo expression systems suggested that activating CFTR inhibits ENaC channels so that activation of CFTR and deactivation of ENaC seem reciprocal. Lack of CFTR Cl(-) conductance (g(CFTR)) in the plasma membranes was seen to enhance ENaC conductance (g(ENaC)) and Na(+) absorption from the airway surface liquid causing airway pathology in cystic fibrosis (CF). To determine if these events hold true for a purely absorptive epithelium, we investigated the role of CFTR in regulating g(ENaC) in native human sweat gland ducts. After permeabilizing the basilateral membrane of the duct with alpha-toxin, the relative activities of ENaC and CFTR in the apical membrane were characterized by correlating the effect of activating CFTR with ENaC function. We found that in contrast to reciprocal activities, activating g(CFTR) by either cAMP, cGMP or the G-proteins plus 5 mM ATP was accompanied by a concomitant activation, not inhibition, of g(ENaC). The activation of g(ENaC) appeared to be critically dependent on CFTR Cl(-) channel function because removal of Cl(-) from the medium, blockage of CFTR with inhibitor DIDS or the absence of CFTR in the DeltaF508 CF ducts prevented activation of g(ENaC) by cAMP, GMP or G-proteins. Most significantly, g(ENaC) was dramatically reduced, not increased, in CF as compared to non-CF sweat ducts. These results showed that lack of CFTR in the plasma membranes is not characteristically coupled to elevated ENaC activity or to increased Na(+) absorption in CF epithelial cells. Not only are CFTR and ENaC activated together in duct salt absorption, but ENaC activation depends on functioning CFTR. NaCl is poorly absorbed in the CF duct because CFTR activity appears to impose a loss of ENaC activity as well.     

P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.     

Sweat ethanol concentrations are highly correlated with co-existing blood values in humans

This study compared the concentration of ethanol, both absolute and relative to water content, in sweat and blood. Ten male volunteers consumed approximately 13 mmol (kg body weight)-1 of ethanol. Blood and sweat samples were collected approximately 1, 2 and 3 h following ingestion. Sweat was collected following pilocarpine iontophoresis using an anaerobic technique that prevented ethanol evaporation. In addition, the water content of sweat and blood samples was determined. The correlation between sweat and blood ethanol, expressed in mmol l-1, was r = 0.98. The slope of the relationship was 0.81. When corrected for the water content in each sample, and expressed as mmoles per litre of water, the correlation remained very high (r = 0.97) while the slope increased to 1.01. These results suggest that rapid and complete equilibrium of ethanol occurs across the sweat gland epithelium.     

The cholinergic regulation of potassium (86Rb+) permeability in sweat glands isolated from patients with cystic fibrosis

Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands.     

Sweat testing: review of technical requirements

The sweat test, a quantitative measurement of chloride in sweat, remains a key laboratory test to support the diagnosis of cystic fibrosis. However, because of its delicate execution, sweat test result should be interpreted with biological, clinical and genetic arguments. The following guidelines which we propose, were established in order to harmonize the practices of the sweat test. They are elaborated in a consensual way by biologists from cystic fibrosis reference centers and/or from the working group "Sweat Testing" of the National College of Biochemistry Hospital praticiens, according to the current state of knowledge on the subject, the experiment of the biologists and the recommendations established in the United States and in the United Kingdom.     

Sweat sodium levels in adults with nasal polyps

Nasal polyps occur in 10% of children and 48% of adults with cystic fibrosis. The prevalence of abnormal sweat tests and cystic fibrosis in adults with nasal polyps has not been reported. We therefore performed sweat tests on 35 adults with nasal polyposis seen in two allergists' office practice. Sweat sodium levels ranged from 12 to 65 mEq/L (median = 34). These were considered within the normal range for adults. Abnormal sweat tests and cystic fibrosis were not found in this series of adults with nasal polyps.     

Sweat testing for cocaine, codeine and metabolites by gas chromatography-mass spectrometry

Sweat testing for drugs of abuse provides a convenient and considerably less invasive method for monitoring drug exposure than blood or urine. Numerous devices have been developed for collection of sweat specimens. The most common device in current use is the PharmChek Sweat Patch, which usually is worn by an individual for five to ten days. This device has been utilized in several field trials comparing sweat test results to conventional urinalysis and the results have been favorable. Two new Fast Patch devices have been developed and tested that allow rapid collection of sweat specimens. The Hand-held Fast Patch was applied to the palm of the hand and the Torso Fast Patch was applied to the abdomen or the sides of the trunk (flanks) of volunteer subjects participating in a research study. Both patches employed heat-induced sweat stimulation and a larger cellulose pad for increased drug collection. Sweat specimens were collected for 30 min at various times following administration of cocaine or codeine in controlled dosing studies. After patch removal, the cellulose pad was extracted with sodium acetate buffer, followed by solid-phase extraction. Extracts were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS) simultaneously for cocaine, codeine and metabolites. Cocaine and codeine were the primary analytes detected in sweat. Peak cocaine and codeine concentrations ranged from 33 to 3579 ng/patch and 11 to 1123 ng/patch, respectively, across all doses for the Hand-held Patch compared to 22-1463 ng/patch and 12-360 ng/patch, respectively, for the Torso Fast Patch. Peak concentrations generally occurred 4.5-24 h after dosing. Both drugs could be detected for at least 48 h after dosing. Considerably smaller concentrations of metabolites of cocaine and codeine were also present in some patches. Generally, concentrations of cocaine and codeine were higher in sweat specimens collected with the Hand-held Fast Patch than for the Torso Fast Patch. Drug concentrations were also considerably higher than those reported for the PharmChek Sweat Patch. The predominance of cocaine and codeine in sweat over metabolites is consistent with earlier studies of cocaine and codeine secretion in sweat. Multiple mechanisms appear to be operative in determining the amount of drug and metabolite secreted in sweat including passive diffusion from blood into sweat glands and outward transdermal migration of the drug. Additional important factors are the physico-chemical properties of the drug analyte, specific characteristics of the sweat collection device, site of sweat collection and, in this study, the application of heat to increase the amount of drug secreted.     

Identification of sudomotor activity in cutaneous sympathetic nerves using sweat expulsion as the effector response

Summary In a warm environment at ambient temperatures between 25° and 38°C (relative humidity 50%–60%) the relationship between sympathetic activity in cutaneous nerves (SSA) and pulses of sweat expulsion was investigated in five young male subjects. The SSA was recorded from the peroneal nerve using a microelectrode. Sweat expulsion was identified on the sweat rate records obtained from skin areas on the dorsal side of the foot, for spontaneous sweating and drug-induced sweating, using capacitance hygrometry. Sweat expulsion was always preceded by bursts of SSA with latencies of 2.4–3.0 s. This temporal relationship between bursts of SSA and sweat expulsion was noted not only in various degrees of thermal sweating but also in the sweating evoked by arousal stimuli, or by painful electric stimulation. The amplitude of the sudomotor burst was linearly related to the maximal rate of increase of the corresponding sweat expulsion, the amplitude of the expulsion and the integrated amount of sweat produced for the duration of the expulsion. The results provide direct evidence that sweat expulsion reflects directly centrally-derived sudomotor activity.     

Iontophoretic beta-adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo.

With the advent of numerous candidate drugs for therapy in cystic fibrosis (CF), there is an urgent need for easily interpretable assays for testing their therapeutic value. Defects in the cystic fibrosis transmembrane conductance regulator (CFTR) abolished beta-adrenergic but not cholinergic sweating in CF. Therefore, the beta-adrenergic response of the sweat gland may serve both as an in vivo diagnostic tool for CF and as a quantitative assay for testing the efficacy of new drugs designed to restore CFTR function in CF. Hence, with the objective of defining optimal conditions for stimulating beta-adrenergic sweating, we have investigated the components and pharmacology of sweat secretion using cell cultures and intact sweat glands. We studied the electrical responses and ionic mechanisms involved in beta-adrenergic and cholinergic sweating. We also tested the efficacy of different beta-adrenergic agonists. Our results indicated that in normal subjects the cholinergic secretory response is mediated by activation of Ca(2+)-dependent Cl(-) conductance as well as K(+) conductances. In contrast, the beta-adrenergic secretory response is mediated exclusively by activation of a cAMP-dependent CFTR Cl(-) conductance without a concurrent activation of a K(+) conductance. Thus, the electrochemical driving forces generated by beta-adrenergic agonists are significantly smaller compared with those generated by cholinergic agonists, which in turn reflects in smaller beta-adrenergic secretory responses compared with cholinergic secretory responses. Furthermore, the beta-adrenergic agonists, isoproprenaline and salbutamol, induced sweat secretion only when applied in combination with an adenylyl cyclase activator (forskolin) or a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, aminophylline or theophylline). We surmise that to obtain consistent beta-adrenergic sweat responses, levels of intracellular cAMP above that achievable with a beta-adrenergic agonist alone are essential. beta-Adrenergic secretion can be stimulated in vivo by concurrent iontophoresis of these drugs in normal, but not in CF, subjects.     

Effect of a low-carbohydrate diet on plasma and sweat ammonia concentrations during prolonged nonexhausting exercise

The purpose of this investigation was to examine the effect of low body glycogen stores on plasma ammonia concentration and sweat ammonia excretion during prolonged, nonexhausting exercise of moderate intensity. On two occasions seven healthy untrained men pedalled on a cycle ergometer for 60 min at 50% of their predetermined maximal O₂ uptakes ( _max) firstly, following 3 days on a normal mixed diet (N-diet) (60% carbohydrates, 25% fat and 15% protein) and secondly, following 3 days on a low-carbohydrate diet (LC-diet) (less than 5% carbohydrates, 50% fat and 45% protein) of equal energy content. Blood was collected from the antecubital vein immediately before, at 30th and at 60th min of exercise. Sweat was collected from the hypogastric region using gauze pads. It was shown that plasma ammonia concentrations after the LC-diet were higher than after the N-diet at both the 30th and 60th min of exercise. Sweat ammonia concentration and total ammonia loss through the sweat were also higher after the LC-diet. The higher ammonia concentrations in plasma and sweat after the LC-diet would seem to indicate an increased ammonia production, which may be related to reduced initial carbohydrate stores.     

Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Singnificance for geneticists

We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kb>T as homozygotes of compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat testnegative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. © 1995 Wiley-Liss, Inc.