INFLUENCE
OF WEATHER
VOLUME, J.
13.
BLACK,
JZ.D.,
AND D~ZLLAS,
ON BLOOD
WHOLE AND
DENSITY,
PLASMA
BTlOOD CHLORIDE”
A. H. BRADEE, M.D.,
HOUSTON, TEXAS
T IS a matter of common knowledge that the weather has a profound I influence upon the allergic mechanism. Many persons suffering with asthma can foretell with considerable accuracy an impending weather change before it becomes recognizable to the nonallergic person. Most of them will volunteer the st,at,ement that their asthma is worse when kveather changes occur, and part.icularly do they say that, damp weather Thwr arc many allergic.persons, also, whose aggravates their condition. symptoms may be prominent during the fall, winter, and early spring but who remain quite free of symptoms during the hot dry weather of summer as WC see it in the southwest. Many of these, we believe, present symptoms or are free of them largely dependent upon weather conditions and not bccausc of seasonal exposure to allergens or bacterial invasion. In some instances it has been possible to show that a foodsensitive person may 1)~ able to cat the offending food in moderate amount during hot, dry weather but, must omit it from the diet in variable weather of othtlr seasons. With the advent of air conditioning there have been investigations into the c#ect, on l’ollt~ii-scnsitivc persons of control of pollen, temperature, and humidity. Rappaport, Nelson and Walker1 made such a study and found some attacks of asthma occurring during storms although the pollen, temperature, and humidity were adequately controlled. They suggest that the barometric pressure and ionization of air might possibly play an etiologic r61e.
Although it may be admitted that, weather conditions greatly influence allergic reactions, no study seems to have been made to determine how weather conditions affect the allergic mechanism. This doubtless is due t,o our ignorance of the mechanism of the allergic reaction, but it is possible that information regarding the influence of weather changes might throw some light on the allergic reactions themselves. On the assumption t,hat local edema is an underlying condition in the allergic reaction, it would seem logical to assume that any condition which would cause a flow of fluid from the blood to the tissues would predispose to an allergic attack or make one possible from a specific allergen which, of itself, might be insufficient to provoke an attack. On *Read .Uler’gy,
before Kansas
the City,
Twelfth .kn~~&l May 12, 3936.
Meeting 39
of
the
Association
for
the
study
,,f
this basis we have studied the red cell volume, blood density and chloride content of whole blood under varying conditions of humidity and baromet,ric pressure. Elsewhere2 we have reported the findin, 0’ ol’ an increase in blood concentration in art,ificiallp induced hay fever, showing that apgroximntely 3.5 per cent of the fluid portion of the blood left the vcssrls immcdiatcly on the onset of nasal symptoms causin, v an increase in the tissue fluid (Fig. 1). This is similar to the concentration which occurs in the anaphylactic guinea pig.” One of us (J.H.B.), sensitive to ragweed, was used as the subject for cell volume st,udies whit h were made outside the ragweed season and in the absence of allergic syml&oms. Blood was secured From a yc+i bc-
Fig.
l.-Changes
in
blood
clensity
in
hny
fever
(artificially
induced).
tween four and five hours after a light midday meal. All conditions regarding the intake of food and fluid, work, and room temperature were kept within narrow limits. The variable factors were the barometric pressure and the humidity. Blood was drawn without a tourniquet to avoid changes in concentration due to venous stasis and 1 C.C. of a 1.6 per cent sodium oxalatc solution (which is practically isotonic) added to 5 C.C. of blood was used as an anticoagulant. Under the above conditions hcmatocrit dctcrminations were made. It was recognized that red cell volnmc is ~)robably an unsatisfactory index to total blood volume, but it was bclicvcd that changes in the ccl1 volume would serve as a reliable criterion of proportionate chang,rcs in the plasma. Fig. 2 shows a scrics of cell volun~c dctcrminations with the barometric pressure and relative humidity readings taken within an hour of the time the blood was drawn for examination. It will be seen
that, while there is wide variation in the pressure and humidity readings, the hematocrit readings were pract,ically constant. Recognizing that the cell volume determination is p)robably t,oo crude a method to detect changes which might occur, we did a series o? blood density determinations usin, e the method of Barbour and Hamilton.* This consists of the timing of the fall of a 10 c. mm. drop of blood through 30 cm. of a mixture of sylene and bromobenzcnc. The falling time of a similar size drop of pot~assium sulphate of known specific gravitv is detcrmincd and the specific gravity of the blood calculated.
Fig.
2.-Constant
cell
volume
uninfluenced
by
humidity
or barometric
pressure.
It is a method which permits the use of a small drop of blood, can be quickly and frequently repeated, and detects very small changes in density. Fig. 3 illustrates a series of such determinations made on one of LIS (J.H.B.) together with the barometric pressure, the relative humidity, vapor pressure, and temperature readings obtained at t,hc same time. The conditions under which the blood was drawn were similar to those in the cell volume determinations. It may be seen that definite changes in blood density occurred from day t,o day extending over a range from 1.0566 to 1.0598, which is equal to a change in water content of 6.4 per cent. The barometric pres-
sure curve is strikingly similar to the blood density curve, an increase The relative in density occurring at the time of increased pressure. humidity and the vapor pressure readings were just the reverse, high The tempc&urc showed density being associated with low humidity. only small variations (a range of 7” C.) and, while a rise in temperature is associated with a decreased densit,y, is not, so definite as are the other factors. Blood chloride determinations in allergic persons have been reported by several investigators. Most of these made no menCon of whether determinations were made during altacks or in the free intervals, and possible yariations in blood none seemed to take into consideration
TEMP. BLOOD DENSITY
VAPOR PRESSURE RELATIVE HUMIDITY BAROMETER
Fig.
3.-Blood
density
and
weather
conditions.
volume. Since it is apparent to any one who has observed asthmatic attacks that there must be considerable water loss from muscular activity and perspiration, changes in blood concentration would be expected. Since it is known that the plasma contains much more chlorides than do the red cells, a loss of fluid should cause a definite reduction in the whole blood chlorides. Barber and Oriel” state that the whole blood chlorides are diminished in acute and chronic allergy, that this finding group and that it varies with t,he is most constant in the asthma-prurigo exacerbation or remission of symptoms. But apparently no blood rolume studies were made to determine whether the findings were part of the allergic reaction or solely a result of loss of blood fluid.
We have done whole blood chloride determinations on 90 allergic patients. Twenty-four of them were having mild attacks of asthma at Of the the time of the examination; the others were free of symptoms. 24 showing symptoms 10 showed vary& 0 degrees of blood concentration as determined by cell volume. Of t,hCsc, 4 showed low chlorides and 2 were above the normal limits. Eight showed no evidence of concentration but 6 of these had low chloride content. Six showed increase in plasma content, and of Ihcs~~, 4 had high chloride readings while the other 2 w’crc low.
90 80 70 60 50 40 30 20 10 400 Fig.
4.-Blood
chlorides
and
red
cell
volume.
The chloride content of the blood of 66 persons free of allergic symptoms at the time of examination showed wide variations, ranging from 310 mg. to 544 mg. The average of thrst? readings was 416 mg. In contrast with these was an avcragc reading of 426 mg. in the patients with mild asthmatic attacks. Of the 66 persons tested in their free periods 10 had some degree of blood concentration with low chloride readings, while 30 had low chlorides with no evidence of concentration. The others had normal readings with no evidence of blood concentration. Fig. 4 shows a series of chloride and cell volume determinations made, on one of us (J.H.B.) to determine daily fluctuations. These were made
44
THE
JOURNAT,
OF
Al,r,ERGY
under the conditions recited above in the discussion of cell volume determinations. It may be seen that while the ccl1 volume remained rclatively constant the chloride content varied from 485 mg. to 400 mg. CONCLUSIONS
There are daily variations in blood concentration which may be determined by the method of Barbour and Hamilton. These occur in tha absence of allergic symptoms and may be related to humidity and barometric pressure. Cell volume determinat,ions do not de&t these variations. Blood chloride determinations should bc correlated with blood volume at least in attempting to show differences in and between attacks of asthma. The variation of whole blood chloride content of the blood is considerable under normal conditions, and significance should be attached only to wide differences. REFERENCES 1. Rappaport,, B. Z., Nelson, T., and IValker, W. H.: The Effect of Low Relative Humidity at Constant Temperature on Pollen Asthma, J. ALLERGY 6: 111, 1935. 2. Black, J. H.: Weather Conditions and Blood Plasma Volume, Texas State J. Med. 31: 516, 1935. 3. Black, J. H., and Kemp, H. A.: Blood Density in Guinea Pig Anaphylaxis and Am. J. Clin. Path. (to be published). in Hay Fever Artificially Induced, 4. Barbour, H. G., and Hamilton, TV. F.: The Falling Drop Method for Determining Specific Gravity, J. Biol. Chem. 69: G25, 1926. 3. Barber, H. W., and Oriel, G. H.: Biochemical Investigations in Allergic Conditions, Brit. M. J. 2: 880, 1928. DISCUSSION
DR. CHARLES N. HEKSEL, Dr. Braden has not told us chloride and blood volume basic sodium chloride intake
St. Paul.-These figures are interesting, but whether he had controls as far as the blood are concerned. Were these people on a and fluid intake?
DR. OSCAR SWINEFORD, JR., University, Va.--I am terribly sorry that Dr. Braden did not permit himself the luxury of a hypothesis. I have permitted myself that luxury and I may as well express it here. It is this: baromet,ric pressnre frequently varies 10 to 20 mm. of mercury or 140 to 250 mm. of water. With this variation in ext,ernal pressure there must be some adjustment of the int,ravasculnr osmotic pressure. Without this adjustment one would expect cxtravasation into the tissues when the barometer falls and dehydration of the tissues when it. rises. Metabolites would presumably collect in the tissues during the period of extravasation. The mechanism with which the normal person adjusts himself to these changes is not known. Nor is the reason for the failure of the abnormal person to adjust himself known. Sodium chloride is only one constit,uent of the blood stream responsible for its osmotic tension. In the normal individual the chlorides fluctuate widely under a number of conditions difficult to control. I believe that much more conclusive information could bc obtained by studying at short intervals the osmotic tension of the whole blood with some of the
BLACK
AND
BRADEN:
INFLUENCE
OF
WEATHER
45
dialyzing apparatuses recently described. I hope the authors have the facilities and the desire to pursue this further, as their problem is most important. I)R. IZOBERT W. LANSON, Los Angeles.-For a number of years I have been interested in climatic effects upon allergic conditions. At certain seasons of the year, notably September to October, and again in the spring, there seems to be an increase in respiratory allergic symptoms. This occurs in the non-sensitive as well as in the sensitive individual and with or without contact with the specific excitants. Changes in the clinical or physical condit,ions of the blood may cause t,hesc symptoms, or be the result of them. At the same periods of the year, especially the fall, the incidence of so-called colds in the normal population shows a very sudden rise. I refcr to the type of complaints which do not require medical attention, and so do not, ordinarily get into vital statistics. The U. S. Public Health Service has published such a study (Public IIewlth Rciports, Vol. 47 : 1815, September 2, 1932)) and they show very little variation of incidence in the six sect ions of the country represented. I believe that some climatic factor is responsible for the sudden onset of respiratory symptoms in the normal, and at the same time in the allergic, group. The latter group does not commonly present symptoms of a true infection. I wish to compliment Dr. Black and Dr. Braden for emphasizing that one need not assume a new bacterial infection to account for a sudden aggravation of symptoms. I should like to make this prophecy, that no matter where or how you may be treal.ing asthma and hay fever the phenomena mentioned will be repeated again this fall in the normal as well as in the allergic population.
DR. Br,:\cK.-Contrary to Dr. Swineford’s statements, wc did have a hypothesis, but we had it first,. The hypothesis on which we started this work was that there probably was a change in blood density due to weather conditions, and wc were hoping to find that with an increase in humidity and a drop in baromet,ric pressure we would find an increased density of the blood which would mean the fiuid had gone out into the tissues. On the assumption Ihat had taken place with an increased edema, it would take much less excitnnt to bring about an allergic attack than at other times, and we felt the weather might influence the asthmatic person in the particular manner that, when at one time there is more fluid in the tissues, an individual can be more easily drawn into an att,ack than ot,htkrwise; but the results were directly contrary to that. The third slide showed the density and rclativc hum&y and the barometric prcssnre; Ihat when the humidit,\- went down and t,hc barometric pressure went, ul), the tlciisily also went, up. When the humidity went up higher, WC cxpcctcd thal the individual was more likely to have an attack, t,hat t,hc blood density would go up, showing more blood going into the tissue: but. the exact opposite occnrrcd, so wc had to abandon our hypothesis. In regard to Dr. Hensel’s statements t.hat these patients should have been on a basic diet, I think possibly wc did not make ourselves clear as to why we were doing this. We were not attempting to show the blood chloride content of individuals under optimum circumstances, but that the chloride determinations under ordinary circumstances were not very dependable. The last slide which was shown was a series of 21 consecu-
46
TIIE
JOURNAI,
OF
>\LLERGY
tivc chloride determinations, done on myself on 21 consecutive days. These were done without a tourniyucl.. L\ tourniquet on the arm for five minutes will make as much as 30 per cent, difference in plasma volume. If that is true, the tourniquet has a trrmendous influence; and these were made without the tourniquet, simply puttin, v the needle into the vein. They were done outside the pollen season when WC were having no allergic reaction at all, four hours after a light midday meal; and while that was not always exactly the same, neither is the preceding meal in the ordinary individual. When doing this blood chemistry-no food for four hours and no fluid for two hours-under those circnmstanccs you find the chloride running from 400 mg. to 485 mg. Recentl? t,here was an article in 1.11~Jo~rtwL of Labo~c~tory mad Uiniin which it said ~rl Xedzcanc, on blood changes followin g hyperthermia, there were cbangcs in blood chloride in a range of 2 per cent, and here we arc finding in a normal individual under cont.rollcd circumstances a variation of 85 mg. The onl?- reason for prescntirfg this is the fact that if w-e are going to do blood chemistry detcrminatlons on these individuals, we ought, to recognize first that, blood volume does play a part and individuals suffering a large water loss in asthmatic a,ttack should have that taken into consideration; and, second, that the variations are so wide that one ought to draw conclusions onl>- on wide variations.