VENTILATORY FUNCTION TESTS. III. RESTING VENTILATION,METABOLISM, AND DERIVED MEASURES

By HARL W. MATHESON AND JOHN S. GRAY

(From the Department of Physiology, Northwestern University Medical School, Chicago)

(Submitted for publication December 3, 1949; accepted, February 13, 1950)

One important phase of respiratory function isthe ventilation of the lungs with an alternatingflow of respired air. The rate at which this proc-ess is carried on, expressed in terms of the volumeof air, either inspired or expired, per minute, isthe pulmonary ventilation. The maximum ratewhich this process can attain is the ventilationcapacity. The difference between the two, com-monly expressed as a percentage of the capacity,is appropriately called the ventilation reserve (1).It represents that portion of the capacity whichis not in use and therefore available as a reserveto be called upon when the necessity arises.The common denominator of most disturbances

in the ventilatory function of the pulmonary bel-lows is a loss of ventilation reserve. This may oc-cur in two ways. First, the reserve may be re-duced because the ventilation capacity is impaired.In the preceding two reports of this series (2, 3),procedures for measuring the degree of impair-ment of ventilation capacity and for analyzing itscauses were considered. Second, the reserve maybe reduced by an increase in pulmonary ventila-tion. The present report is concerned principallywith procedures for measuring this type of dis-turbance and differentiating some of its causes.Any kind of increase in pulmonary ventilation

may be called a hyperpnea since this term is non-committal with respect to the type or cause. How-ever, hyperpneas in general may be divided intotwo types, depending upon whether they are nor-mal responses to increased metabolic demands orare compensatory responses to disturbances in in-ternal or external environment.

In metabolic hyperpneas, the increase in pul-monary ventilation is in direct proportion. to theincrease in metabolism as measured by 02 con-sumption. The ratio of ventilation to 02 consump-tion, therefore, does not change. This ratio, ex-pressed as the liters of air respired per 100 cc. of02 consumed, is known as the ventilation equiva-lent for 02 (4-7). In thyroid disease as well as

in moderate physical exercise the ventilatory re-sponses are so adjusted to the metabolism thatthe ventilation equivalent for 02 remains essen-tially unchanged (8).By contrast, in compensatory hyperventilation,

the increase in pulmonary ventilation is out of pro-portion to the metabolism. As a result, the venti-lation equivalent for 02 is materially increased.This is true of simple anoxia, of CO2 inhalation,of metabolic acidosis, of fever, and of various typesof reflex hyperpneas (8).

Simultaneous determination of the pulmonaryventilation and 02 consumption and calculation ofthe ventilation equivalent for 02, therefore, per-mits a quantitative evaluation of the degree of dis-turbance in pulmonary ventilation, and should aidin the identification of possible causes. It was thepurpose of the present study to determine the re-liability of such determinations and to establishnormal values.

METHODS

A sample of 100 healthy young male medical studentsserved as subjects for this study. Their age and physicalcharacteristics are summarized in Table I. The plan ofthe experiment was to make duplicate determinations ofthe various tests at one sitting, and then to repeat thisprocedure approximately one week later. The volun-tary ventilation capacity and the vital capacity were de-termined according to the previously standardized tech-niques already described (2, 3). These determinationswere made on a separate occasion from the others, sinceresting conditions are neither required nor possible.The pulmonary ventilation and Os consumption were

determined simultaneously under resting conditions. This

TABLE I

Characteristics of satnple of 100 male medical students 74

Mean St. d. C. var.

Age, years 23.3 3.4 14.6Height, inches 70.5 2.2 3.1Weight, pounds 158.0 18.9 11.9Surface area, sq. m. 1.88 0.13 6.9

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TABLE II

Results of tests applied to 100 normal subjects

First day Second day

Mean St. d. C. var. Mean St. d. C. var.

Voluntary ventilation capacity, V.V.C. 160.9 19.5 12.1 168.6 19.2 11.4Vital capacity, V.C. 5.18 0.68 13.2 _Resting ventilation, R.V. 7.56 1.23 16.2 6.87 0.97 14.1Restng metabolic rate, R.M.R. 274 32.4 11.8 275 32.9 11.9Resting ventilation reserve, R.V.R. 95.3 0.88 0.92 95.9 0.72 0.75Resting ventilation equiv., R.V.E. 2.78 0.45 16.2 2.51 0.30 11.9Respiratory rate, R.R. 10.5 3.0 28.5 10.1 3.1 30.7Tidal volume, T.V. 770 220 28.5 730 190 25.9

involved a period of resting in a chair for at least 10 min-utes, followed by an additional five-minute period of re-

clining on a cot with the back rest elevated at a 30 de-gree angle. No precautions were taken with respectto previous fasting, since true basal conditions are aninconvenient limitation on routine clinical use. The re-

sults revealed that the preliminary rest was somewhattoo short; a 20-minute period in the semi-reclining posi-tion would have been superior, as shown by Soley andShock (9).The Benedict-Roth basal metabolism spirometer was

used with the soda-lime absorber in position (in con-trast to ventilation capacity and vital capacity tests), andwith the spirometer filled with O. Several minutes wereallowed for the respiratory excursions to stabilize. Asix-minute run was used, at the end of which the mechani-cal ventilometer, thermometer, and barometer were readand the subject's mouthpiece removed. After a short in-terval to refill the spirometer and adjust the instru-ments, the procedure was repeated.The 0, consumption was obtained in the usual fashion

from the slope of the tracing and expressed in cc. per

minute, STPD (760 mm. Hg 00 C.); the pulmonary ven-

tilation was determined from the ventilometer and ex-pressed in liters per minute, BTPS (Body Temperature,Pressure and Saturated), taking into account the effectof the soda-lime on water vapor tension. The respira-tory rate, or frequency, was also read from the tracingand the mean tidal volume calculated.The following formulae were used to calculate the two

derived measures, resting ventilatory reserve (RVR) andthe resting ventilation equivalent for O0 (RVEo2):

RVR in per centVoluntary Ventilation Capacity - Resting Ventilation

Voluntary Ventilation Capacityx 100

RVEo, in L./100 cc.

Resting Ventilation in L./min., BTPS X 100Resting 02 Consumption in cc./min., STPD

RESULTS

The repeated application of the various test pro-cedures to 100 healthy adult male subjects yieldedthe results summarized in Tables II and III. Themeans, standard deviations, and coefficients ofvariation for each type of test and for the meanof two trials on each of two days are included inTable II; the reliability coefficients based upontest repetition, both within and between days, areincluded in Table III. The last columns of TableII, which represent the means of duplicate trialson the second day, are preferred as a source ofnorms.The resting pulmonary ventilation showed a

tendency to fall during successive trials (from7.89 to 7.24 on the first day and from 7.03 to 6.71on the second). In part this reflects the inade-quate preliminary rest period, and the growingfamiliarity with the test and its procedures. Thenormal mean is taken at 6.87 L./min. (BTPS)with a coefficient of variation of 14.1 per cent;95 per cent of the healthy young adult population,therefore, should lie within the limits of 5.90 and

TABLE IIIRdiability coefficients

Reliability coefficients

Within one dayBetweendays

1st day 2nd dayVoluntary ventilation capacity .728 .825 .754Resting pulmonary ventilation .753 .917 .628Resting ventilation reserve - - .404Resting metabolic rate .868 .904 .S83Resting ventilation equivalent for 0s .646 .749 .556Vital capacity .975 - -

Resting respiratory rate .879 .953 .886Resting tidal volume .754 .924 .782

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7.84 L./min. The reliability of the determinationimproved considerably on the second day, reachinga coefficient of 0.917.The resting metabolic rate, or 02 consumption

also showed a tendency to fall slightly during suc-cessive trials within one day (from 280 to 268 onthe first day and from 281 to 270 on the second).The normal mean is taken as 275 cc. of 02(STPD) consumed per minute, with a coefficientof variation of 11.9 per cent. The reliability co-efficients within days are consistently high, butthat between days fell to 0.583. This is presum-ably due to the fact that resting, rather than rest-ing and fasting, conditions were observed.The voluntary ventilation capacity yielded a

normal mean of 168.6 L./min. (BTPS) with acoefficient of variation of 11.4 per cent. Thus,these three primary measurements show vari-ability of nearly the same degree.The respiratory rate and tidal volume averaged

10.1 per minute, and 730 cc. (BTPS) respectively.Their variability was considerably higher, how-ever, for the respective coefficients of variationwere 30.7 and 25.9 per cent. Their distributionsare skewed, as revealed by a mean tidal volumeof 730 cc. as compared with the ratio of the meanresting ventilation to the mean respiratory rate ofonly 680 cc. The reliability coefficients, however,are quite good.The resting ventilation reserve, a derived meas-

urement, is the difference between the resting ven-tilation and the ventilation capacity, expressed as apercentage of the latter. Inasmuch as the ventila-tion capacity was determined at a different timethan the resting ventilation, the reserve has beencalculated only from the means obtained on the dif-ferent days. Even this, however, should affect thereliability coefficient adversely. The normal meanis taken as 95.9 per cent, with a standard deviationof 0.72 per cent, and a coefficient of variation ofonly 0.75 per cent. The extremely low variabilityis, of course, due to the fact that the resting reserveexpressed in liters per minute is so large in com-parison with the variability of the resting venti-lation.The second derived measure is the ventilation

equivalent for O2, which expresses the volumeof air breathed for each 100 cc. of 02 absorbed.The normal mean is 2.51, with a coefficient ofvariation of 11.9 per cent, which is nearly identi-

cal with those of the elements of the ratio. Itsreliability is less than that of its elements, however.The correlation coefficient for the relationship

between the resting ventilation and resting meta-bolic rate was found to be 0.592. The statisti-cally fitted regression equation was

RV = 0.0175 RMR + 2.01

This equation implies that the ventilation equiva-lent for 02 is not constant, but a hyperbolic func-tion of the resting metabolic rate. However, be-cause the metabolic rate, which is the independentvariable in the above regression, is subject to er-ror, the resulting regression equation is biased inthe direction of departure from the simple directproportion required for a constant ventilationequivalent for 02 This bias can be overcome byextending the range of metabolic rate. This ex-tension occurs in hyperthyroid states and may beproduced experimentally by moderate physicalexercise, in neither of which is the ventilationequivalent appreciably altered (8). It is con-cluded, therefore, that in health the resting ven-tilation equivalent for 02 remains constant withinthe range established by its standard deviation asshown in Table II.

DISCUSSION

Comparison of the present normal values forthe various ventilatory function tests with valuespreviously reported in the literature is difficult be-cause of the diversity of procedures used. Inmany instances coefficients of variation of 25 to 50per cent are evident in the reported results, in-dicating a failure to standardize methods. Fur-thermore, corrections for temperature, pressure,and water vapor are commonly either not made ornot disclosed. Inasmuch as gas volumes of BTPSare about 25 per cent greater than at STPD, thisitem alone can produce a consistent error which isbeyond the range of normal individual variation.

In the case of metabolic rate, or 02 consump-tion, the present resting values may be comparedwith basal metabolism standards. According tothe Boothby and Sandiford standards, the basal02 consumption for male subjects averaging 23years old and 1.88 sq. m. in surface area shouldbe 266 cc. per minute. This is only slightly less

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*than the present resting values of 275 cc. perminute.The present norms apply only to the male sex.

Preceding reports of this series have demonstratedan appreciable sex difference in voluntary ventila-tion capacity and vital capacity (2, 3). Both aver-age in women only 70 per cent of the value formen, leaving the ventilation capacity per liter ofvital capacity (the capacity ratio) the same inboth sexes. Both resting ventilation and metab-olism are likewise lower in women than in man.No significant sex difference has been reported fortheir ratio as calculated in the ventilation equiva-lent for 02, implying that both are reduced pro-portionately in females. Judging from the data ofShock and Soley (10) and the basal metabolismstandards, the reduction is less than that for venti-lation and vital capacities. Thus the resting ven-tilation reserve should be slightly lower in women.The various ventilatory function tests investi-

gated in this and preceding reports are for themost part long known tests. The object of re-examining them has been twofold: first, to providenormal values based on a healthy young popula-tion and employing better standardized procedures,and second, to elaborate a rationale for their com-bined use in the clinical examination of disturb-ances of ventilatory function. In the past thetests have been used more or less in isolation withdisappointing results, since none of them providesall the desired information (11). When usedsystematically and in combination, however, theyshould be rather effective in a) identifying the na-ture of a ventilatory disturbance, b) evaluating thedegree of such disturbance, and c) differentiatingpossible causes.A common form of ventilatory disturbance is a

reduction in ventilatory reserve, the accompany-ing subjective symptom of which is dyspnea. Thismay be identified and its severity measured by thepresent tests. Furthermore, many possible causesmay be differentiated. In the first place, the ven-tilatory reserve can be reduced by either of twomajor causes, namely, a reduction in ventilationcapacity, or an excessive ventilation. These pos-sibilities can be readily differentiated and thecontribution of each evaluated by the present tests.Furthermore, each of these major possibilities canbe further analyzed by means of the remainingtests of the series. A reduced ventilation capacity,

for example, may be due to excessive pulmonaryresistance, to muscular weakness, or to a smallvital capacity. In the latter case the capacityratio (3) remains unaltered; in the former casesthe capacity ratio will be reduced. Also muscularweakness can be identified by means of the maxi-mum expiratory pressure (3). The other majorpossibility, namely, excessive ventilation, can beidentified as a metabolic hyperpnea, if the venti-lation equivalent for 02 is unchanged, or as acompensatory hyperventilation, if the ventilationequivalent is elevated. The former is a normalresponse to an excessive metabolism; the latteris an adjustment of ventilation designed ta com-pensate for some abnormality in the inspired air,blood pH, body temperature, altered blood pres-sure (both venous and arterial), etc.

This scheme may be presented in the form of aclassification of impaired ventilatory reserve, asfollows:

I. Reduction in resting ventilatory reserve.A. Due to impaired ventilation capacity.

1. With normal capacity ratio.a. Due to reduced vital capacity.

2. With reduced capacity ratio.a. Due to increased pulmonary re-

sistance orb. Reduced muscular force, as shown

by the maximum expiratory pres-sure.

B. Due to excessive pulmonary ventilation.1. With normal ventilation equivalent for

02-a. Metabolic hyperpnea, due to in-

creased metabolism.2. With elevated ventilation equivalent

for 02-a. Compensatory hyperventilation, due

to ventilatory adjustment to someother disturbance.

This analysis, it should be clear, is made interms of physiological function and not in termsof disease entities. Diseases which produce dif-ferent patterns of physiological disturbance inventilatory function should be differentiable on thebasis of this analysis. In any case the type ofdisturbance, its degree, and to a considerable ex-tent, its causes can be evaluated.

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SUMMARY AND CONCLUSIONS

1. Procedures, reliabilities, and normal valuesbased upon 100 healthy medical students are pre-sented for the four primary measurements of vol-untary ventilation capacity, vital capacity, restingpulmonary ventilation, and resting 02 consump-tion; and the three derived measurements of rest-ing ventilatory reserve, the capacity ratio, and theventilation equivalent for 02

2. A scheme is presented for the systematic useof these ventilatory function tests in the analysisof clinical ventilatory disturbances in terms oftheir nature, degree, and causes.

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