716
The ]ournal o[ P E D I A T R I C S
Observations on skin resistance to electricity and sweat chloride content A p r e l i m i n a r y report
Randolph Batson, M.D., "~ William C. Young, M.D., and Frank M. Shepard, M.D. "'~ NASHVILLE, TENN.
A S l M P L ~ test for cystic fibrosis with a high degree of accuracy has yet to be described. In an attempt to develop such a test a technique was devised to measure skin resistance to electricity. We thought that the high chloride content of sweat from children with cystic fibrosis should be responsible for decreased skin resistance to electrical conductivity. Licht, Stern, and Shwachman ~ have reported that sweat collected from such children showed decreased resistance to electrical currents, and Bruyn 1 described a technique for measuring the electrical conductivity of microsamples of sweat. He thought that levels of conductance found in the sweat of fibrocystic children were clearly distinguishable from those of normal children. After measuring skin resistance in many
From the Department of Pediatrics and the Clinical Study Center [or Birth Dejects, Vanderbilt University School o[ Medicine. Aided by a grant #ore The National Foundation. ~Address, Pro[essor of Pediatrics, Vanderbilt University School o[ Medicine, Nashville, Tenn. -x":"~Exehange Fellow in Pediatrics, Royal Caroline Institute o[ Medicine, Stockholm, Sweden.
patients with or without cystic fibrosis, we noted that within the control group there was a racial factor. The skin a n d / o r sweat of Negroes exhibited considerably more resistance to conductivity than that of white children. Following this observation, the investigation was expanded to include a comparison of skin resistance and sweat chloride content in the two races. There have been other reports of racial differences in sweat chloride content. Kuno s found that the chloride content of sweat obtained from Japanese residents in J a p a n was considerably higher than from natives of the Tropics. He presumed that in the Tropics the sweat glands of natives are supplied abundantly with adrenocortical hormones and that the low chloride content of sweat played an important role in the daily life of these natives who benefited by conserving salt. K a w a h a t a * also found sweating to be strikingly diminished in similar natives and felt that the function of the human sweat apparatus was influenced by climate. He found the total number of active sweat glands largest in tropical natives and Japanese born in the Tropics; less in Japanese
Volume 60 Number 5
Skin resistance to electricity and sweat chloride
immigrants in the tropics and those living in Japan proper; and much less in Russians settling in north Manchuria. LaddelP noted that African natives of low economic status had lower salt concentration in the sweat than Europeans tested under the same experimental conditions. He could not determine the role of acclimatization in altering chloride content. He reported, however, that the sweat chloride secreted by the residential acclimatized European was less than that from Europeans tested under artificial conditions to Great Britain but greater than that from Africans trained or untrained for work in the heat. Robinson and his colleagues s found, in comparing 6 Negroes with 5 white adults, that the Negroes' average sweat chloride was higher. However, he pointed out that this was due, in part, to exceptionally high values in 2 Negro men who produced sweat containing 144 and 93 mEq. of chloride per liter, respectively. In reviewing the question of sweat chloride and racial differences, Robinson and Robinson 9 thought "that differences observed by some of these authors were probably dependent upon differences in nutritional state a n d / o r acclimatization to environmental conditions." He had attributed his own results in Negroes to high dietary intake of salt, usually in the form of salt pork. Hsia and his co-workers, a in a study of sweat electrolytes in patients with various types of allergies, compared his results in Negroes and whites. Among the allergic patients he noted that, by the use of the plate method for estimating chloride content, 44 per cent of the Negroes and 62 per cent of the whites had a positive reaction according to his criteria. I-Ie thought that this difference was probably not significant. In the control population, however, 14 per cent of the whites and 7 per cent of the Negroes showed positive reactions. On the basis of this observation Hsia thought that the incidence of elevated sweat chlorides as measured by the plate method was significantly lower among the Negro population as a whole.
MATERIALS
7 17
AND METHODS
Testing equipment and methods were selected largely on the basis of simplicity. A standard ohmeter was used. * A selector switch on the ohmeter permitted measurements over a wide range with the ranges employed for this purpose being R • 100,000t and occasionally R • 1,000. The accuracy of the meter reading decreases as the left (maximum resistance) side of the scale is approached. For this reason an effort was made to obtain readings whenever possible from the right side of the scale. Numerous electrodes were tested, value being placed on simplicity, availability, adaptability, uniform skin contact surface, and uniform distance between electrodes. The electrodes selected consisted of bakelitemounted contact points commonly used as "starters" for fluorescent lights. These afford uniform distance between electrodes and uniform surface contact. Commercially available "starters" have contact points of different metals; differences in conductivity between these metals was insufficient to warrant a corrective factor. The skin over the gastrocnemius was selected as a testing site since this area is convenient and sufficiently abundant in sweat glands. The following procedure was used routinely in measuring resistance of skin a n d / o r sweat. The skin over the gastrocnemius was prepared by wiping the skin with a damp cloth and drying thoroughly. The electrodes were mounted on electrocardiographic rubber-retaining straps by pushing the contact points through the perforations in the strap. The strap was then placed around the greatest diameter of the lower leg with contact points over the gastrocnemius. Two thirds of the lower leg (including the electrodes) was then wrapped with thin plastic strips 2 89 inches wide. Approximately 6 thicknesses w e r e placed around the leg, perfora-
~Triplett Model 630 Volt-Ohm-Millammeter. The Triplett Electrical Instrument Company, Bluffton, Ohio. t " R " represents the resistance read dlreefly from the meter scale; when the " R " X 100,000 range is used, " R " is multiplied by 100,000.
7 18
Batson, Young, and Shepard
May 1962
dren; 53 of these had cystic fibrosis. In the control group there were 150 white children and 79 Negroes. Sweat chloride determinations were made on 133 children, 41 of whom had cystic fibrosis. Forty-six white children and 46 Negro children were in this control group. Early in this study several unusual values were observed in children with brain damage, most of whom had hydrocephalus. Because of the possibility that brain damage produces sweat electrolyte changes, 72 white children with extensive brain damage were tested for skin resistance and 51 for sweat chloride values.
Fig. 1.
tions being made in the plastic by the sharp base of the electrode. This permitted accessibility to the poles without removal of the plastic. A light covering of cloth (a sheet or blanket) was then placed over the lower extremities to diminish the effects of air current. The ohmeter was standardized before each test. After 20 minutes a reading was made, preferably from the right portion of the ohmeter scale with the range selector on R • 100,000. If the meter selector was changed, the ohmeter was again standardized before making another reading. The reading selected was that obtained when there was sufficient pressure to give good contact (Fig. 1). Sweat was collected for chloride determination by the method of Shwachman and Leubner u and also by the iontophoresis method described by Gibson and Cooke. 2 In many instances duplicate collections were made with the use of both methods. Chloride content was determined by the method of Schales and Schales. 1~ Skin resistance was measured in 282 chil-
RESULTS
The original objective of this investigation was to determine whether or not the skin resistance in patients with cystic fibrosis differed from that in other children. The study was extended since many Negroes in the control group showed extremely high resistance to electrical current. Fig. 2 indicates that within the control group differences exist between white and Negro subjects. The skin resistance measurements illustrate the distinction between values in those subject with cystic fibrosis and in those of the control group. Skin resistance of approximately 150 ohms x 10 '~ appeared to be the dividing line between the great majority of subjects with cystic fibrosis of the pancreas and those in the control group. In fact 88.7 per cent of children with cystic fibrosis had values less than 150 x 10 '~ ohms, whereas, in the control group, 90 per cent had values greater than 150 • 103 ohms. Sweat chloride determinations were made on 133 children. Fig. 3 demonstrates the dis-
Table I. The 95 percentile range for individuals in the groups studied
I !
Controls (white)
Controls (Negro)
Cystic fibrosis (white)
Brain damaged (white)
Sweat chloride (mEq./L.) No. of subjects
4.4 to 67.1 46
3.1 to 41.5 51
71.l to 180.3 41
5.7 to 94.2 22
Skin resistance (ohms x 103) No. cf subjects
105 to 494 150
107 to 1242 78
40 to 222 53
34 to 787 72
Volume 60 Number 5
Skin resistance to electricity and sweat chloride
7 19
Table II. Geometric means and the 95 per cent confidence limits
Controls (white) Sweat chloride (mEq./L.) No. of subjects Skin resistance (ohms x 10a) No. of subjects
17.2 (14.6to21.0) 46
228 (214 to 243) 150
Cystic fibrosis (white)
Controls (Negro)
] Brain damaged ] (white)
11.3 (9.4to13.6) 113.2 (105.3 to 121.8) 23.2 (17.2 to 31.2) 41 22 51 365 (318 to 419) 78
tinction between normal children and those with cystic fibrosis. This supports the view of many that this is the most reliable test available for the diagnosis of this disease. These data indicate that there is a group difference between normal white children and normal Negroes; the latter, as a group, have somewhat lower sweat chloride content than normal white children. Further observations are necessary to test the significance of this observation. Table I shows the expected 95 percentile range for sweat chloride content of normal individuals. For example, the "normal" range of sweat chloride values among white children is between 4.4 and 67.1 mEq. per liter. This, of course, does not mean that anyone whose concentration of sweat chloride is outside this range is abnormal, since 1 in 20 individuals would be expected to be outside the range. Such limits give an estimate of predicted values. There were significant group differences among the geometric means and the mean values; 95 per cent confidence limits for these values are indicated in Table II. One can readily distinguish the various populations which were sampled by their sweat chloride content and their skin resistance measurements. Measurements of skin resistance and determinations of sweat chloride were obtained in 92 individuals. Twenty patients had central nervous system disease, 10 patients had cystic fibrosis; while 17 white and 45 Negro children formed the control group. The possible relationship between the skin resistance and sweat chloride in the individual subject was investigated, and clear lack of correlation exhibited in all the groups, except those
94 (84 to 106) 53
164 (136 to 197) 72
with cystic fibrosis, discouraged further statistical analysis. DISCUSSION Measurements of skin resistance in these subjects were made under as nearly standardized conditions as possible. However, the skin resistance values varied slightly in relation to pressure applied to the contact electrodes. The value was recorded after stability of the indicator showed that good electrode contact had been made without undue pressure. We think that "skin resistance" is determined largely by sweat resistance to electricity and that probably this is influenced by the chloride content. The subjects tested showed relatively high resistance immediately after the electrodes were in place and decreasing resistance as
C O N T R O L GROUP
z5
(White and Negro)
2O 15 I0
30 (n w
~5 2o 15
ested = 2 2 9
NORMAL WHITE umber Tested = 150
m a-
~E
z5
- - n
N O R M A L NEGROES N u m b e r Tested = 7 9
4O 35
PIBROCYSTTC DISEASE OF PANCREAS z
zo =5 =0 5 0
N u m b e r Tested = 5 3
. . . . . . . . . . . . . . . . . . . . . . .
SKIN
R E S I S T A N C E IN O H M S X IO3
Fig. 2. Skin resistance.
7 2 0 Batson, Young, and Shepard
so !2
CONTROLGROUP (White and Negro)
i
NORMAL WHITE
,s
Number
iii
Tesled=46
............. Number Tesfed= 4 6
May 1962
4 groups of children; white children in a control group; N e g r o children in a control group; white children with cystic fibrosis; and white children with central nervous system disease. T h e various groups studied could be distinguished both with respect to sweat chloride a n d skin resistance measurements. F u r t h e r studies are u n d e r w a y to determine if the test can be developed to be useful as a screening a n d diagnostic procedure.
iI FIBROGYSTfC DISEASE OFPANCREA~/,//.~/.//,~/~ Number Tested = 41
IN
SWEATCHLORIDE ~4EQ./L.
We are grateful for the assistance of Charles F. Federspeil, Ph.D., who assisted with the statistical analysis of the data.
Fig. 3. Sweat chloride.
sweating o c c u r r e d t o w a r d the end of the 20m i n u t e waiting period. T h e fact t h a t neonates, in w h o m very little sweating occurs, show a high skin resistance supports the hypothesis t h a t skin resistance to electricity is d e t e r m i n e d by the chloride content of the sweat. T h e study of skin resistance as a useful diagnostic m e t h o d in screening patients for cystic fibrosis m a y hopefully be p u r sued since differences in skin resistance were d e m o n s t r a t e d in the 4 groups studied; modification of e q u i p m e n t a n d refinement in testing techniques should m a k e this possible. R a c i a l factors a p p a r e n t l y o p e r a t e d both in resistance to electrical c u r r e n t a n d in sweat chloride values in the white a n d Negro control groups. N e i t h e r low salt i n t a k e nor a c c l i m a t i z a t i o n are likely to have p l a y e d a role in the observed differences since our subjects were all children of a p p r o x i m a t e l y the same economic status. T h e most plausible e x p l a n a t i o n is t h a t the chloride content of the sweat of Negroes is low. If this is true, it m a y largely explain o t h e r racial c h a r a c teristics such as their superior c a p a c i t y for work u n d e r conditions of e x t r e m e heat. s T h e r a r i t y of cystic fibrosis a m o n g Negroes now becomes of even m o r e interest. SUMMARY Skin resistance to electrical c u r r e n t a n d sweat chloride values have been r e p o r t e d in
REFERENCES
1. Bruyn, I-I. B.: The Determination of the Electrical Conductance of Microsamples of Sweat as a Means of Diagnosis of Congenital Fibrocystic Disease, A. M. A. J. Dis. Child. 98: 49, 569, 1959. 2. Gibson, L. E., and Cooke, R. E.: A Test for Concentration of Electrolytes' in Sweat in Cystic Fibrosis of the Pancreas Utilizing Pilocarpine by Iontophoresis, Pediatrics 23: 545, 1959.
3. Hsia, D. Y., DriscolI, S. G., Greenberg, D., Ting-Chien, L., and Gilbert, L.: Abnormal Sweat Electrolytes in Patients With Allergies, A. M. A. J. Dis. Child. 96: 685, 1958. 4. Kawahata, A., and Sakamoto, H.: Some Observations on Sweating of the Aino, Jap. J. Physiol. 1-2: i66, 1950-1952. 5. Kuno, Yas: Human Perspiration, Springfield, Ill., 1956, Charles C Thomas, Publisher. 6. Ladell, W. S. S.: Acquired Heat Tolerance of Temperate Climate Men Living in the Tropics, Internat. Physiol. Congress 18: 320, 1950 (abstract). 7. Licht, T. S., Stern, M., and Shwachman, t{.: Measurement of the Electrical Conductivity of Sweat, Clin. Chem. 3: 37, 1957. 8. Robinson, S., Dill, D. B., Wilson, J. W., and Nielsen, M.: Adaptations of White Men and Negroes to Prolonged Work in Humid Heat, Am. J. Trop. Med. 21: 261, 1941. 9. Robinson, S., and Robinson, A. H.: Chemical Composition of Sweat, Physiol. Rev. 34: 202, 1954. 10. Schales, O., and Schales, S. S.: A Simple Accurate Method for the Determination of Chloride in Biological Fluids, J. Biol. Chem. 140: 879, 1941. 11. Shwachman, H., and Leubner, H.: Mucoviscidosis, Advances in Pediatrics 7: 249, 1955.