PULMONARY VENTILATION IN HEALTH AND DISEASE
ARTHUR TILGHMAN BRICE*
From The Clinical Laboratories of the United States Veterans Administration, Fori Miley,
California, and the Department of Physiology of Stanford University
A bottom line is drawn on the chart connecting the greatest possible number of points
representing the ends of inspirations, in the same manner as that by which the top line
is generally determined. The mean distance between the two lines, representing the mean
respiratory amplitude (M.R.A.) or mean tidal volume for the period of observation, is
measured in terms of cubic centimeters of oxygen by employing the scale for the particular
respiration apparatus used. The respirations per minute are counted over a representative portion of the chart, and the average recorded as the average respiratory rate
(A.R.R.). The minute volume is then obtained by multiplying the mean respiratory amplitude, or tidal volume by the average respiratory rate, Q.V. Minute Volumne =
A.R.R. X M.R.A.
A scatter diagram from the data collected of minute volume on minute oxygen consumption proved to be markedly askew, but a linear and apparently normal correlation
was shown by the plot of the logarithmic values of these variables. The coefficient of
correlation obtained was +0.3879, with a standard deviation of ±0.0268. There is one
chance in 100 that the true value of r will fall outside of the limits of +0.3181 and +0.4550
(Fisher's Z Method).
* Lieut. Colonel, Inf. Published with the permission of the Medical Director, U. S.
Veterans Administration, who assumes no responsibility for the opinions expressed or
the conclusions drawn by the author.
144
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With regard to the normal mechanism linking metabolism and respiration
Knipping and Moncrieff1 have stated that the rates of oxygen consumption and
external respiration change in parallel fashion so that the value of the coefficient
.
... ,.
.
minute 0 2 consumption
.
,,
,
, „. , „
of ventilation, i.e., — : — - — ^
—
remains unaltered: and Ziegler2
: f.
minute O2 respiration
has reported that this index represents a constant for the individual. These
statements imply a high degree of correlation between the rates of oxygen consumption and respiration difficult to reconcile with the known facts and conclusions of physiology, since it is the concentrations of both hydrogen ions and
the C0 2 of the venous blood that regulate the rate of respiration, and the maintenance of equilibrium, represented by the value of approximately 5.6 per cent
of C0 2 in the alveolar air, clearly requires that the changes be relative, so that
the correlation between the two variables may be expected to be linear only on a
relative or logarithmic basis.
In order to test this conclusion by statistical methods, 1005 graphic respiration charts obtained by use of the Sanborn Motor Grafic equipment in routine
basal metabolic rate determinations at the U. S. Veterans Administration
Facility, Fort Miley, California, were assembled and the correlations between
all of the variables involved have been analyzed. The minute volumne of
respiration determinations were carried out by the method advocated by
Ziegler2;
PULMONARY VENTILATION
145
The finding of such a high alienation and low prediction value relationship
between these variables, even on the logarithmic basis, indicates quite clearly
that a number of factors or forces are involved in establishing the level of the
coefficient of ventilation, and that this index, assuming a stable level of respiratory center sensitivity, is probably more properly referable to the state of acidbase equilibrium of the blood than to the state of conditions existing at the
pulmonary interface as was suggested by Anthony 3 . Moncrieff's4 report, that
the coefficient was of little value in the study of pulmonary disease, tends to
support this conclusion.
THE VALUE OF THE COEFFICIENT OF VENTILATION IN HEALTH AND THE
BASAL STATE
PHYSIOLOGIC VARIATIONS IN VENTILATION
An opportunity having been afforded to carry out a number of examinations
on individual medical students not under basal conditions in the Department of
Physiology Stanford University, the following observations of interest were
made:
G. C. came to the physiology laboratory directly from the mid-term examination.
Though a short prescribed rest was taken, his coefficient of ventilation at the start of the
test was 7.9. Within sixteen minutes, he had become more at ease, and the value declined
to 3.7.
Among the records submitted by students, one was found, that of W. E., age 22, which
showed a buccal temperature of 96.6T., a B.M.R. within normal limits, and the very low
value of the C.V. of 1.7. He stated that his temperature had been found subnormal on
occasions, and that his blood pressure tended to be low. He volunteered to submit to a
protracted period of observation, and several days later his respiration was recorded by
Sanborn apparatus for thirty minutes. His B.M.R. remained constant during the period.
The C.V. calculated for each minute varied, with no noticeable cyclic tendency, between
the limits of 8.6 and 4.0, the mean for the period of observation being 5.7. This is believed
to represent the case of an individual of very labile respiratory center sensitivity. The
physiological variation observed in this single individual exceeded the extreme range in
the basal state found in the entire series of pathological cases to be reported in this paper.
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Moncrieff4 concluded from his study of controls that the mean coefficient of
ventilation is 4.0 in health and the basal state, and shows a variation between
different normal individuals of ± 2 5 per cent. Dr. Ziegler has kindly turned over
to me the original records which he took at the Boise, Idaho, Facility of the
Veterans Administration, from seventy-three young male adults, enrolled in the
Civilian Conservation Corps, admitted to hospitalization for treatment of
minor ailments. These records were made under standard basal conditions
after over-night rest in the hospital. The age range was 18 to 37, average 22.5
years. The mean value of the coefficient of ventilation was 4.0, standard
deviation ± 0 . 8 , indicating a normal variability of ± 2 0 per cent, slightly lower
than reported by Moncrieff. These findings are in such close agreement, that
there can be hardly any doubt that the value of 4.0 represents a satisfactory mean
for the basal state, and that the "Ventilograph" described by Philip Reichert
and Herman Roth 6 has been correctly designed.
146
ARTHUR TILGHMAN BRICE
The variability of individual reaction differences to oxygen deficiency, pointed out by
H. G. Armstrong6 and others, may be accounted for by the individual limits of the respiratory center sensitivity.
T H E FINDINGS I N
DISEASE
The determination of the coefficient of ventilation has been carried out as a
routine procedure in all cases referred to the Clinical Laboratory for B.M.R.
determination from the wards and Diagnostic Center of the United States Veterans Administration Facility, Fort Miley, California, for a number of years.
In selecting case material from the data thus made available, after discharge of
the patients from hospital, to illustrate the pulmonary ventilation levels in
disease, many cases have been excluded on the grounds of complicating or
secondary diagnoses such as might invalidate the conclusions with reference to
ventilation in the particular clinical entities under consideration. The conclusions are therefore based on uncomplicated conditions and only such entities
are reported on at this time as the mass of data available has seemed to justify.
THYROID DISEASE
There were available 73 records from 37 patients suffering from thyroid disturbances.
The plot of the C.V. on the B.M.R. values shows an interesting relation of ventilation
to the severity of the disease. Starting from about the value of the C.V. which we have
accepted as normal, i.e. 4.0, the C.V. fell as the B.M.R. either fell or rose, and approximately in proportion to the deviation of the B.M.R. from zero. The relationship is clearly
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A small amount of the student material has been studied with reference to
the effect of postural changes on the value of the coefficient of ventilation. The
mass of evidence is not great, but shows higher C.V.'s recumbent than sitting,
and an upward trend during recumbent recovery after a period of standing.
From one subject whose experimental data was such as to permit valid calculations, the C.V. fell during a brief period of exercise and rose afterward to a higher
level than before.
Knipping and Moncrieff1 have reported an accidental observation of an
elevated C.V. in sleep in one of their controls. A similar observation has been
made in one case in our pathological series. Respiratory center depression in
sleep would account for these findings.
The data collected which have been referred to, comprising 1005 tests on
males, yield a mean C.V. of 3.55 ±1.104. Thirty four tests on females are
available, showing a mean C.V. of 4.14 ±0.903. Both groups comprise cases of
varied disease conditions, so that comparison is of doubtful meaning. However,
the difference is 3.7 times the standard error of the difference, and therefore must
be considered statistically significant.
The Chi square method applied to the total mass of data available from males
indicates that there is a tendency for higher ventilation values to appear in the
younger age groups, although the probability of such a correlation occurring by
chance is high (P = 0.423), and the conclusion is subject to the same criticism,
in that disease conditions constituted variable factors in all cases.
PULMONARY VENTILATION
147
statistically significant for elevated B.M.R. and highly probable for depressed B.M.R., as
has been stated in a preliminary report (F. W. Weymouth and A. T. Brice 7 ).
The effect of treatment is illustrated well in a group of nine cases selected on the basis
of improvement in B.M.R. shown prior to discharge from the hospital. The group included the following diagnoses: one colloid goitre, one hypo-thyroidism, two exophthalmic
goitres, and five hyper-thyroidisms. The first tests recorded in this group showed a mean
C.V. of 2.4, a deviation from normal ventilation of minus 40 per cent. After treatment,
which was surgical in five of the cases and medical in four, the mean C.V. for the group
was found to have returned to the normal value of 4.0.
A small group of simple goitres, colloid and non-toxic adenomatous, showing B.M.R.
values generally close to normal, appeared to be definitely out of line with other thyroid
conditions. Eight such cases showed values above the C.V. upper normal limit, determined as plus one times the standard deviation. The group mean C.V. of 5.3 indicates a
deviation above the normal mean of plus 32 per cent.
In asthma and emphysema ventilation is significantly depressed. Bronchitis shows
normal or high normal values. In pulmonary tuberculosis values of the C.V. below the
lower normal limit, determined as minus one times the standard deviation at C.V. = 3.2,
appeared in more than one-third of the cases, although but slight depression of ventilation is indicated by the group mean of 3.5 for fifteen cases.
CARDIAC AND CIRCULATORY CONDITIONS
The pulse and blood pressure data taken from the forty cases included in this group at
the times of the examinations indicate that the cases were well compensated at least when
the C.V. determinations were made. The ventilation levels in the small number of cases
in which heart rates were more rapid than 80 per minute are indistinguishable from those
of the remainder of the group. With the possible exception of blood pressure in the hypertensive group, none of the variables studied, namely heart rate, systolic, diastolic, and
pulse pressures, appear to be related to the ventilation level as indicated by the C.V.
There is a definite tendency for higher ventilation levels to appear in hypertension.
Eleven cases in which the principal diagnosis was hypertension showed a group mean
C.V. of 4.4. This value is doubtfully above the normal mean. Statistical comparison
between this group and Dr. Ziegler's normal group, which has been referred to, indicates
that such a difference might be expected to occur 8.36 times in 100 by chance if no real difference is present.
Seventeen principal diagnoses of myocardial damage showed a mean C.V. level of 2.6,
a depression below the Ziegler normal group level which is clearly statistically significant.
Twelve cases diagnosed arteriosclerosis also showed a group mean of 2.6, also significantly
below Ziegler's normals.
In view of these findings, a comparison was made between myocardial damage and
arteriosclerosis cases combined as one group and the group of hypertensive cases. The
difference was clearly statistically significant, and there could hardly be any probability
of such a difference occurring by chance. This conclusion suggests the possibility of using
the measurement of the ventilation level as a means of evaluating the proportionate effect
of myocardial damage, arteriosclerosis, or hypertension in individual cases in which two
or more of these factors may be present.
MISCELLANEOUS INDIVIDUAL RECORDS
One case of terminal uremia showed the very low C.V. value of 1.9. Two cases of liver
damage, one of cirrhosis, and one of carcinoma, showed values of 2.3, well below the lower
normal limit. The highest value recorded, C.V. = 7.3, appeared in a case of blindness and
obesity. Hemorrhoids and obesity also showed a high C.V. = 4.9. A patient weighing
287 lbs. diagnosed hypopituitarism with diabetes, nephritis, and hypertension showed a
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RESPIRATORY CONDITIONS
148
ARTHUR TILGHMAN BRICE
high level of ventilation, C.V. = 6.2. Two cases of Addison's disease showed C.V.'s of 2.5
and 2.9.
A group of eight cases, including all such cases encountered in the series, in which headache was the principal complaint and primary clinical diagnosis all showed ventilation
levels in the lower range. The mean C.V. of this group was 2.45, a value significantly below the Ziegler normals. This finding is considered of special interest in view of the recent
success of Alvarez8 with the oxygen treatment of migraine.
SUMMARY AND CONCLUSION
My thanks are due to Dr. Edwin E. Ziegler for supplying me with data which have
provided the basis for establishment of the normal coefficient of ventilation criterion.
REFERENCES
(1) SNIPPING, H. W., AND MONCHIEPF, A.:
Ventilation equivalent for oxygen.
Quart. J. Med., 1 (new series): 17,
1932.
(2) ZIEGLER, E. E.: A new measurement of
Oxygen absorbing power. Med.
Annal. Dist. Columbia, 2: 225, 1933.
(3) ANTHONY, A. J.: Untersuchung
ventilograph. An improved recording ventilometer and its applications.
J. Lab. and Clin. Med., 25: 1091,1940.
(6) ARMSTRONG,
H.
G.: Principles
and
Practice of Aviation Medicine. The
Williams & Wilkins Co., Baltimore,
Md., 1939.
uber
(7) WEYMOUTH, F. W., AND BRICE, A. T.:
Lungenvolumina und Lungenventilation. Deutsch. Arch. F . Klin. Med.,
167: 129, 1930.
On the relation between the coefficient
of ventilation and the metabolic rate
in thyroid disease. A preliminary
report. Proc. Soc. Exper. Biol, and
Med., 46: 596, 1941.
(4) MONCBIEFF, A.: Tests for respiratory
efficiency. Special report No. 198 of
the Medical Research Council, London, 1933.
(5) REICHERT,
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(8) ALVAREZ, W. C : New treatment of
migraine. Proc. Staff Meet. Mayo
Clinic, 14:173,1939.
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Physiologic ventilation may be defined as the percentage of respired oxygen
that is absorbed through the pulmonary interface. Changes in underlying metabolic processes operating to determine the level of activity of the respiratory
center are reflected in changes in value of the coefficient of ventilation.
The coefficient of ventilation normally varies inversely as the B.M.R., rising
in value as the B.M.R. falls, and falling as the B.M.R. rises. In thyroid disease
normal or elevated ventilation has been found in cases of simple and non-toxic
adenomatous goitres. In other thyroid conditions the normal relationship is
disturbed, the ventilation falling as the B.M.R. either falls or rises.
In cardiac and circulatory conditions the level of ventilation is generally
lowered except in hypertension. The conclusion from statistical methods of
reasoning suggests the possibility of using the level of ventilation, as measured
by the C. V., as a means of evaluating the relative severity of damage and hypertension factors in these cases.
The finding of depressed ventilation in a short series of cases of headache is
reported as a matter of record.