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George R. DeMuth, M.D., William F. Howaft, M.D., and Bruce M. Hill, Ph.D.

Departments of Pediatrics and Mathematics, University of Michigan, Ann Arbor

I. LUNG

VOLUMES

T

HE GROWTH of the lung and its function

have been studied by a variety of tests

in 147 normal children. In 101 children the

tests were repeated in about 16 months to

obtain longitudinal data. For some of these

tests no datum from normal children was

available. More importantly, data from

lon-gitudinal studies were not available for any

of the tests. Repeated studies on the same

individual permitted us to look at the

in-dividual’s growth and to compare it to that

of the group by the use of covariance

analy-sis. The performance of a spectrum of tests

of different lung functions on each child

allowed us to compare the growths of these

different functions. From these

compari-sons we have obtained patterns of growth.

Lastly by the use of this particular group

of subjects we have examined the

relation-ship of lung function to intelligence,

scho-lastic achievement, and physical strength.

The following tests were carried out:

(a) lung volumes (vital capacity, expiratory

reserve volume, and functional residual

ca-pacity); (b) forced flow rates (peak

inspira-tory and peak expiratory flow rates and the

flow rates at the points where 50% and 75%

of the vital capacity have been expired);

(c) intrapulmonary gas distribution (the

nitrogen clearance during oxygen

breath-ing, the oxygen equilibration index, and the

single-breath oxygen test); and (d) lung

diffusing capacity (carbon monoxide

breathing method). For comparison of the

results to body size and growth, the age

and various anthropomorphic

measure-ments were obtained. The results of

stand-ardized tests of intelligence, academic

achievement, and muscle strength were

available on the majority of these students.

In this, the first paper, we will

character-ize the population of children, discuss the

methods of analysis, and present the (lata

on lung volumes.

SUBJECTS

The 147 subjects for the study were

stu-dents at University School (Ann Arbor,

Michigan). They were in grades from the

junior kindergarten through the 12th and

ranged in age from 4 to 18 years. From

each class above kindergarten 10 subjects

were randomly selected for testing. This

was not possible in the kindergarten and

below where the subjects were chosen by

the teacher for their expected ability to

co-operate. In all about one-third of the

students in the school participated. The

medical history as recorded by the school

physician was examined for each child. The

available information included his and the

school nurses’ observations as well as

his-tory forms filled out by the parents. Those

children with chronic or recurrent lung

dis-ease were excluded. The children were

Caucasian, except for one Negro child.

Intelligence tests (Stanford-Binet,

Wechs-ler Intelligence Scale for Children,

\Vechs-ler Adult Intelligence Scale) and the

Cali-fornia Reading Achievement Tests are

rou-tinely given in this school. Grip Age was

obtained on children in the third grade and

higher. For this study we used the results

of those tests that were obtained at the

time of our second series of tests, if

avail-able, or the nearest preceding one.

At the time of pulmonary testing the

fol-lowing measurements of physical size were

made: (1) height (without shoes) in

centi-meters; (2) weight (without shoes, but

schoolroom clothing) in kilograms; (3)

sit-ting height in centimeters; (4) biacromial

width in centimeters (by calipers); (5) chest

This study was supported by Grant A-3575 from the National Institute of Arthritis and Metabolic

Diseases.

(2)

SUPPLEMENT 163

dimensions in centimeters (by calipers) at

the end-tidal or resting position: (a) A-P

diameter at xyphi-sternal junction, (b) A-P

diameter at angle of Louis, (c)

transthor-acic diameter at level of xyphi-sternal

junc-tion, (d) sternal length-suprasternal notch

to xyphoid. The surface area was

calcu-lated by use of a nomogram based on the

formula of Dubois and Dubois.1 The age

was rounded off to the nearest month and

expressed as a decimal fraction.

All tests of each series were carried out

on a majority of the subjects during a

single examination in which the tests were

performed in a systematic order. In a few

of the smaller children the testing was split

into two parts and done separately, usually

on succeeding days. The first series of tests

on the 147 subjects was spread over a

20-month period (July, 1959, to April, 1961).

During this time ten subjects had repeated

studies done 2-4 weeks after the initial

study. Beginning in February, 1962, all of

the 147 subjects who were available were

asked to participate in another series of

tests. One hundred three were still in the

school; two declined to participate. The

time between examinations varied from 10

to 18.5 months, the median being 15.3

months. Ninety-five per cent were at least a

year apart.

METHOD AND EQUIPMENT

Vital Capacity and Expiratory

Reserve Volume

A stainless steel Krogh spirometer was

constructed with a curved end. Knife edges

were used at the axis of rotation. The

mov-able top portion was counter-balanced by

adjustable weights. The rotation of the top

was measured by the use of a Microsyn No.

1C-020B variable inductance angular

trans-ducer, the output of which was rectified to

give a direct current potential proportional

to the position. For the vital capacity and

expiratory reserve the output was recorded

on a Mosley X-Y recorder using a time base.

The spirometer was calibrated through the

range of use with a 50 ml syringe. It was

virtually linear. The characteristics of this

spirometer are given in the fifth paper in

this series.2

During the examination the subject was

allowed to breath normally for a few

breaths and then perform the vital capacity

maneuver. The spirometer was then rinsed

with fresh air, and a second trial was done.

The time between tests was less than 5

minutes. The higher of the two values was

selected and then corrected to BTPS.3 The

expiratory reserve volume was obtained

from the same tracing and similarly

cor-rected.

Functional Residual Capacity

A measurement of the functional residual

capacity (FRC) was obtained in the test of

diffusing capacity.4 The subject rebreathed

into a bag in a “box” during forced

hyper-ventilation. The dead space of the system

was known. The volume of the bag and its

changes during equilibration were obtained

from the spirometer to which the “box” was

connected. The helium concentration was

measured after the bag and dead space had

been allowed to equilibrate and

continu-ously during the rebreathing process by

circulating the gas through the Cambridge

Helium Katharometer. In this test

rebreath-ing at a high ventilatory rate was continued

for about 50 seconds. The calculation was

as follows:

VFRC = (V50 X He0) - (V., X He,) He,

Vs = volume of bag and dead space

He = helium concentration

Subscript 0 = at start of test; subscript

= final value. No correction was made

for helium absorbed. This test was carried

out in duplicate, and the mean values

reported.

The lung space occupied by the helium

after 45 seconds of hyperventilation should

be very close to the functional residual

capacity in normal children. Equilibration

is probably nearly complete by 15 seconds

(3)

carbon monoxide concentration against

time. This technique, however, is an

ab-breviation of the usual helium rebreathing

method and may not be applicable to

dis-eased subjects. Its validity for studying

growth in normal subjects is apart from its

ability to measure accurately the FRC. An

estimate of its ability for the latter

pur-poses can be obtained by comparing its

results with those obtained by other

methods.

METHODS OF ANALYSIS

In studying the relationship of the results

of the lung function tests to independent

variables, two methods of statistical

analy-sis were customarily used. The first was the

calculation of simple or multiple ordinary

regressions; the second was an analysis of

covariance.5 The calculations of ordinary

regression were made to compare the data

of one series with those of the other, to

examine general relations among the

vari-ables, and to compare our data with those

of others who have used this form of

analysis.

The covariance analysis is a refinement

of ordinary regression in which one looks

at the individuals’ growth lines rather than

at the group growth line. In this analysis,

as in ordinary regression analysis, one

as-sumes that the dependent variable is a

linear function of the independent variable.

For example, one assumes that the log vital

capacity is a linear function of the log

height, characterized by a slope () and

intercept (a). In covariance analysis one

assumes that different individuals have the

same slope or , which slope measures an

intrinsic property of the relationship

be-tween the variables. The individuals may

have different intercepts or a’s. The a

meas-ures a characteristic of the individual and

may be interpreted as a measure of his

height-adjusted vital capacity. In the ideal

circumstance the slopes would all be

paral-lel, and the spread of values at any point

would be due to the a’s. Each person would

maintain his own position within the group.

A further assumption is that the

loga-rithm of an individual’s measured lung

volume fluctuates randomly about the value

of his “true” line and that all such

fluctiia-tions are independent with mean zero. On

each occasion two readings of the

func-tional residual capacity were taken, which

allowed us to obtain a relatively

uncon-taminated measure of the basic variability

of the observation (of a given person at a

given time). The measure that we used was

a sample variance from the deviations of

such observations about the mean of the

pair and is called the estimate Sd2 of the

duplicability variance ,j2. In addition, the

variability of the means of such pairs from

the lines fitted by covariance analysis yields

another sample variance called the

esti-mated residual variance S,.2 which estimates

the residual variance o2. If the assumptions

underlying the analysis of covariance held

exactly, we would have O2 = % d2 since

rr2 is based upon the average of two

obser-vations, each with variance Cd. However,

these assumptions only hold in an

approxi-mate sense, and Sr2 will tend to be inflated

due to non-linearity and variability of

from person to person.#{176}

When the increments in the independent

variable (e.g., log height) are small, the

estimated regression coefficient or slope

()

from covariance analysis is sensitive to

even small systematic changes in the

de-pendent variable (e.g., log VC). As an

ex-ample, in this study the systematic change

between the vital capacity tests in the two

series for boys, as estimated by the

differ-ence in intercepts between the two series

using a common slope, was approximately

0.004. This difference did not appear sig..

nfficant; but when the second series was

adjusted down 0.004 log units to agree in

intercept with the first series, the covariance

slope based on this adjusted data was

de-creased by about 0.1 units in the log system

oThe ratio Sr’ to 52 is sometimes used to test

the underlying assumptions. The values here are

high. We are aware that these assumptions do not

hold exactly, but nevertheless feel that they hold

sufficiently well to yield an appropriate analysis

(4)

BOYS

90%

MEAN

10 S 90%

MEAN

90190

ISO, 80

70 70

160 160

50 ISO

140 40

30 130

20 20

110 110

tOO 00

90 90

Fic. 1. The heights of the subjects in relation to their ages. Points connected by a solid line represent

two measurements on the same individual. The dotted lines connect points representing the 10th, 50th,

and 90th percentiles from a growth table.

4 5 6 7 8 9 0 II 12 3 14 IS 16 17 8 ‘9

AGE IN YEARS

890112I3 I I 7 ‘en

AGE IN YEARS

SUPPLEMENT 165

HEIGHT IN CM HEIGHT IN CM

200 200

G/RLS

and then agreed roughly with the pooled

slope 2.81. Thus a systematic difference

even as low as 0.004 can materially affect

the covariance slope. It is unknown

whether the 0.004 difference is an artifact

or whether it represents a small but real

increase in the level of VC at any given

height. We suggest in this case that it is

an artifact (perhaps due to calibration) but

have no definite evidence.

It is always possible to estimate the

sys-tematic difference (whatever its source)

be-tween the two series by the foregoing

method. Generally such differences have

very little effect on the estimated slope or

residual variance from ordinary regression,

and so we have neglected this adjustment

in our discussion of ordinary regression. As

noted, the adjustment may be crucial in

determining the slope from covariance

analysis. When the adjustments are made,

the covariance slope becomes very nearly

equal to the pooled slope while the residual

variance from the covariance analysis barely

changes; thus generally it is sufficient to

obtain the pooled slope and treat it as the

adjusted covariance slope, using the

resid-ual variance from the unadjusted

covari-ance analysis. Since the latter is typically

much smaller than the residual variance

about the ordinary regression, we have

substantially increased our ability to

pre-dict lung volume as a function of height.

RESULTS

The “Normality” of the Subjects

Figures 1 and 2 show the heights and

weights of these subjects against age for

each sex. The heavy lines connect points

representing the mean, 10th and 90th

per-centiles from the tables of Meredith,

pub-lished in a standard text.6 Light lines

con-nect values on the same individual. It will

be noted that in 5 subjects the second value

was less than the first. These drops, though

small, must represent measurement errors.

The children appear to be normal in these

(5)

BOYS

WEIGHT IN KG.

GIRLS

/

41/2 6 3 14 7 eVa 41/2 6 7

AGE IN YEARS AGE IN YEARS

Fic. 2. The weights of the subjects in relation to their ages. Points connected by a solid line represent

two measurements on the same individual. The dotted lines connect points representing the 10th, 50th,

and 90th percentiles from a growth table.

IS 112 166

heavy for their heights and ages. The

in-telligence of the children was above the

general population level. The mean I.Q.

was 129, with a range from 97 to 197.

Lung Volumes

The vital capacity (VC) and functional

residual capacity (FRC) data from the two

series of tests were first examined by

com-paring the results of regression analyses of

the volumes on height (separately for boys

and girls). For either lung volume and

either sex the slopes and intercepts for the

two series were not significantly different.

The data from the two series were added

together for some of the remaining analyses.

Thus, on such combined data more than

one observation on most individuals were

included.

The results of the analyses of vital

capac-ity against various body measurements are

given in Table I (separately for each sex).#{176}

* ‘Flie estimated standard deviation about a regres-sion line is taketi as the square root of the estimated

WEIGHT IN KG

In Figures 3 and 4 the distribution of the

vital capacity against height for each sex

are shown with a log-log plot. The light

lines connect observations on the same

child and illustrate his growth in

compari-son to the group’s growth. Isolated dots

represent children who were not retested.

The heavy lines represent the calculated

regression line and parallel lines 2.0

stand-residual variance. The standard deviation of the original variable can be expressed as a fraction of the predicted value (median) by the equation

SD(V)

----‘---

ln,10S.I). Pred. (1)

when the standard deviation was obtained after taking logarithms to the base 0. Using 0.00077 as the residual variance from the covariance analysis of log \‘C on log height (boys) we obtain SDc .306 /0.00077

(6)

TABLE I

ANALYSES OF VITAL CAPACITY AND PHYSICAL MEASUREMENTS

Indep. Variable Number Correlation Coefficient Reridual Variance Regression Coefficient (Stand. Error) Coefficient Intercept Boys (2) Boys (3) Boys (4) Boys (5) Girls (2) Girls (3) Girls (4) Girls (5) Boys (5) Girls (5) Boys (1) Boys (5) Girls (I) Girls (5) Boys (4) Boys (5) Boys (1) Boys (3) Girls (3) Boys (2) Boys (5) Girls (2) Girls (5) Boys (5) Girls (5) Boys (5) Girls (5) Boys (5) Girls (5) 121 72 49 121 139 88 51 139 121 139 72 121 88 139 49 121 72 72 88 121 121 139 139 121 139 121 139 121 139 Height Height Height Height Height Height Height height Age Weight Biaeroniial Sitting height Surface area JHeight & age Jlleight & age ,1Height & weight fHeight & veight Jlleight & biacrom itil fhleight & ibiacromial height & age & weight Height & age & weight Height & age & biacromial Height & age & biacromial Height & age & weight & biacromial Height & age & weight & biacromial .944 962 .930 .950 925 .937 923 .933 .918 892 .930 .933 .898 .914 .905 .906 .783 .865 .905 .948 .947 .918 928 952 .936 .953 .940 952 .933 .956 942 .953 .936 .956 .943 148497 .00294 .00457 .00355 101806 .00407 .00329 .00377 .00572 .00599 197136 .00467 147763 .00481 .00614 .00648 570386 .00979 .00608 139587 .00376 109678 .00408 .00342 .00364 .00335 .00344 .00346 .00379 .00321 .00333 .00336 .00367 .00321 .00334 51.35 2.817 2.807 2.810 42.21 2.892 2.664 2.818 1.160 0.895 62.56 0.980 53.20 0.938 2.593 2.557 71.22 2.450 2.631 3016. 1.466 2529. 1 .450 2.265 0.247 2.283 0.192 2.027 0.290 1 .914 0.328 2.379 0.441 2.776 0.039 1 .422 0.260 0.301 1.444 0.178 0.318 1 .939 0.224 0.385 2.290 0.193 -0.008 1.313 0.245 0.271 0.227 1 .503 0.187 0.334 0.116 1 .64 .096 .162 .085 1.49 .116 .159 .093 .046 .039 2.970 0.035 2.818 .036 .178 .109 6.87 .170 .134 93. .046 93. .050 .252 .107 .241 .080 .293 .104 .257 .087 232 .221 .180 .139 .375 .104 102 .324 .077 .086 .311 .107 .220 .271 .081 .138 .390 .105 .106 .223 .331 .078 .088 .135 -4726 -2 .67714 -2.66172 -2.66612 -3728 -2.88793 -2.40082 -2 .73104 2.22379 2.42455 176. 1.84902 209. 1.85953 -0.45036 -0.38363 -2677. -1 .20837 -1.59516 -1150. 3.26117 -829 3. 21310 -1.7398 -1.79525 -1.43371 -1.30088 -2.38921 -2.69718 -0.41069 -0 .45516 -1.58495 - 1.77905 -0.44944 -0 .44559

Boys (5) 121

Girls (5) 139

Boys (5) 121

Girls (5) 139

Boys (5) 121

Girls (5) 139

(7)

6000

5000

4000

3000

2000

100 110 120 I0 i4o I0 I0 I. 80 90

HEIGHT IN CM

Fic. 3. The vital capacity In relation to height (boys) on logarithmic scales. Points connected by a solid

line are on the same subject. The dashed lines indicate the calculated regression line and two

stand-arc! deviations on either side.

LUNG VOLUMES

ard deviations on either side (from the

ordinary regression).

The results of ordinary regression

analy-ses of the functional residual capacity data

are given for each sex in Table II. The

FRC values plotted against height are

shown on logarithmic scales in Figures 5

and 6 in a manner similar to that for the

vital capacity. The systematic difference

between the two series is 0.018. This is not

significant but is greater than that for the

vital capacity. The variance obtained from

the study of the duplicability was 0.01146

L2. The standard deviation of duplicates is

0.107 L which is 6.55% of the mean value.

As noted in the presentation of the

meth-ods of analysis the regression coefficients

obtained from covariance analysis are very

sensitive to small systematic differences

when the change in the independent

vari-ables is small. For this reason the

coeffi-cients are not given. The residual variances

VITAL CAPACITY

IN ML.

obtained from these analyses are valid and

important. The residual variances from the

covariance analyses for the log vital

capac-ity on log height are 0.00077 for boys and

0.00117 for girls. The corresponding figures

from the ordinary regression are 0.00345

and 0.00377. Thus the covariance analyses

reduce the residual variances about 78%

(boys) and 69% (girls) below those obtained

from ordinary regression analyses. For the

log FRC on log height the residual

vari-ances from covariance analyses were

0.00441 (boys) and 0.00335 (girls) which

are about half those obtained from ordinary

regression analyses.

The calculation of regression lines after

logarithmic transformation shows a

rela-tionship such as the following for vital

ca-pacity and height:

Log VC = b X log height + a (Equation 1)

The antilog of the foregoing gives

(8)

GIRLS

6’

V/,-110 20 130

SUPPLEMENT 169

VITAL CAPACITY IN ML

5000

4000

3000

2000

1000

750

100 140 150 160 ITO 180

HEIGHT IN CM

Fic. 4. The vital capacity in relation to height (girls) on logarithmic scales. Points connected by a solid

line are from the same subject. The dashed lines indicate the calculated regression line and two standard deviations on either side.

In the relation of vital capacity to height,

the sizes of the “b’s” or exponents in the

ordinary regression equations are similar

to some previously published.7-9 We did

find the a factor (intercept in Equation 1,

constant multiplier in Equation 2) was

dif-ferent for the two sexes (t = 3.0, p < .001).

This indicates that for the same height girls

have statistically significant lower vital

capacities than boys. This finding was

sus-pected by Engstrom et al.7 but could not be

demonstrated statistically from their

find-ings.

In order to make an easy comparison of

our data with some other reports of studies

of normal children7’1 Table III has been

prepared using our formulas from the

or-dinary regression analyses of the log lung

volume on log height and their suggested

formulas, some of which used age and

weight as well as height. This gives

pre-dicted values for the VC and FRC for

8-and 14-year-old boys and girls of normal

heights and weights. The predicted values

from tile other studies fall within our mean

± 1 SD, except for tile small FRC

pre-dicted by Bernstein’s formula for 8-year-old

boys and except for the large FRC’s

ob-tained from Helliesen’s and Cook’s formulas

for the 14-year-old girls. Helliesen noted

that his functional residual capacities

seemed large, and these data are included

in Cook’s report. Aside from these

discrep-ancies the predicted values are similar,

al-though there were differences in technique.

The values predicted from Cherniack’s

paper are calculated from his regression

equations. Much higher values were

ob-tained from his nomograms.

(9)

Correlation Variable . Coefficient Residual . arianee Regression . Coefficient St. ( Error . intercept oefficient Boys Height Sitting height Surface area Age Vital capacity Height Age Height Weight Height Biacromial .881 .836 .866 .850 .881 .883 .881 .889 .00940 .01262 .01052 .01163 .00986 .00932 .00949 .00892 2.928 2.576 1.481 1.163 .992 2.329 .263 ‘3.0429 - .0414 1 .875 1 .061 160 .172 .087 .073 .054 .465 191 585 203 .450 .425 -3.13596 -1.65581 3.04548 2.00328 -0.189190 -2. 10856 -3.31805 -2.43371 Girls height Sitting height Surface area Age Vital capacity height Age Height Weight .874 .870 .842 .862 .846 .884 .874 .00645 .00661 .00791 .00701 .00744 .00600 .00647 2.538 2.350 1.261 0.837 0.795 1 .551 0.355 2.828 -0.104 134 .126 .076 .047 .047 348 377 .126 -2. 32046 -1. 26188 3.1)3540 2.29031 0.49115

- 0. 55753

-2.77990

170

physical size measurements are related after

logarithmic transformation, the exponent

(b) becomes of interest, for it indicates the

dimensional relationship between the

vari-ables. Volume and, indirectly, weight are

three dimensional quantities; surface area

is two dimensional; and height and

biacro-mial width are one dimensional

measure-ments. Age has one dimension only (time).

When the lung volume is related to any one

of these variables, the value of the

ex-ponent, as in Equation 2, does approach

the ratio of the dimensional natures of the

variables. For example, in tile regressions

of the lung volumes on height, biacromial

diameter, sitting height, or age, tile

ex-ponents are approximately 3/1, or 3. For

the lung volumes on surface area the

ex-ponent is approximately 3/2, or 1.5. For

lung volumes, weight, or another lung

vol-ume the exponents are about 3/3, or 1. If

the exponents are adjusted for their

dimen-sional qualities by dividing the slope of the

volume on linear measurements by 3, that

TABLE II

(10)

SUPPLEMENT 171

TABLE III

COMPAHISON OF PREDICTED VAit:s

.4gc Present

Sex Weight height Data Engstrom Bernstein Ildiiesen Cook Cherniaek

(!/r.)

_____

_____

_____ ____

I?ital (‘opacity

Boy S 27.3K 130 cm. I ,880 ml. 1867 ml 1922 ml 1902 ml 1932 ml 2025 ml

(1 ,639-2, 156)*

Boy 14 48.8K 163cm. 3,549 3480 3307 3641 3831 3671

(‘3,094-4,071)’

Girl 8 26.4K 128cm. 1,611 1790 1764 1820 1726 1738

(1,401-1,848)’

(;irl 14 49.2K 160cm. 3,021 3305 3061 3452 3312 3176

(2,623-3,480)’

Functional Residual Capacity

Boy 8 27.3K 130cm. 1,132 1023 878 1247 1175

(905-1,415)’

Boy 14 48.8K 163 cm. 2,195 1953 1943 2410 2478

(1,745-2,743)’

Girl 8 26.4K 128cm. 1,066 978 900 1193 1161

(880-1292)’

Girl 14 49.2K 160cm. 1,878 1851 1755 2283 2346

(1,550-2,275)’

* \lea,i ± I standard deviation.

on areal measurements by 3/2, and that on ratio does not greatly reduce the limits of

volume measurements by 1, then the values normality. The standard deviations of the

can be compared (see Table IV). It is in- groups are 0.076 and 0.079 and those about

teresting that when tile regression for lung

volume is calculated simultaneously against TABLE IV

two or more independent variables, tile RATIOS OF l)IIENsIoNALIY ADJUSTED ExIONENTS

sum of the adjusted exponents is also equal

Functional

to about one. The significance of these Vital

Residual

values in respect to growth will he dis- Capacity

apaci1y cussed later.

The expiratory reserve volume was ex- Boys Girls Boys Girls

amined as a fraction of tile vital capacity.

For boys the means was 0.3213; the stand- Height .94 .94 .98 .85

ard deviation, 0.0762; the standard error of Sitting height .82 .88 .86 .78

Surface area .98 .97 .99 .84

the mean, 0.0069. For girls the comparable Age 1.16 .90 1.16 .84

values were 0.3269, 0.0788, and 0.0067. Tile Vital capacity .99 .80

difference between the mean values was Biacromial .85

not significant (t* = 0.578; 0.5 < p <0.6). Weight .98 .94

height & age I (10 .95 1.04 .87

The correlations of this ratio with body Height & weight .97 .97 .97 .84

height, surface area, age, and vital capacity Height & biacroinial .94 .94 .98

are significant, but not striking (Table V). hleight, age, weight 1.04 .98

Tile highest correlations are found with hleight, age,

hiacromial I (10 .95

age. However, the use of age to predict the hleighit, age, weight,

(11)

FRC(ML)

5000

4500 BOYS

4000

3500

3000

2500

1500

#{149}1

I00 130 40

HEIGHT IN CM.

Fic. 5. The functional residual capacity in relation to height (boys) on logarithmic scales. Points

con-nected by a solid line are from the same subject. The dashed lines indicate the calculated regression line and two standard deviations on either side.

160 ITO

172

the lines are 0.072 and 0.076 for boys and

girls, respectively.

COMMENT

Studies of the growth of the external

thoracic dimensions from birth to

adult-hood in relation to the body growthl2

sug-gest that after birth the lung volume does

not increase as a linear function of body

size (as indicated by physical

measure-ments) even after logarithmic

transforma-tion. Above about 100 cm of height or age

4 years the relationships can be simplified

by logarithmic transformation. A third

de-gree polynomial function of a physical

size measurement (e.g., height) also yields

a good approximation to the lung volume

data. However, the use of the logarithmic

relationship appears better for several

rea-sons. It is simpler than the general third

degree polynomial, involving fewer

param-eters. Secondly, the residual variances by

the two methods are not much different.

Thirdly, the population of lung volumes at

a given size is positively skewed; hence, the

log transformation acts to normalize the

data. Finally, the “true” regression is very

likely convex in the range studied. The

log-arithmic transformation then tends to

lin-earize what is otherwise a quite complex

relationship.

The single variable which gave the best

correlations with lung volumes was height.

Almost as high correlations are found with

surface area. No advantage to the use of

(12)

in-TABLE V

REoltsssIoN ANALYSES OF THE EXPIRATORY RESERVE VOLUME

VITAI CAPACITY

Independent .

Variable Sex Number

Correlation .

Coefficient

Standard . .

Demation

t Value of

. Regression

Age Boys

Girls

121

139

.351

.283

.072*

.076t

4.09

3.46

Height Boys

Girls

121

139

.318

.208

.073

.077

3.66

Q.49

Surface area Boys Girls

121

139

.311

.166

.078

.078

8.56

1.97

Vital capacity Boys

Girls

121

139

.341

.215

.072

.077

3.95

%.57

SUPPLEMENT 173

* SD of group= 0.0762. t SD of group=0.0788.

volves an additional calculation.#{176} A second

reason for the preference of height is that

weight due to fat (especially in the

abnor-mal with obesity) is thought to have an

ad-verse effect on the lung function. Thirdly,

with chronic lung disease growth is often

disturbed, and it is probable that the

growth of the lung will more nearly follow

the height than the weight.

The estimates of residual variance

ob-tained from the ordinary regressions reflect

tile variations of the data around the fitted

lines. The estimated residual variances from

tile covariance analysis are smaller because

allowances are made for a quality in the

subject, viz., his inherent deviation from

the mean of a group of his size. The more

nearly the individuals’ growths are parallel

to the common growth line, the smaller

will be the residual variance obtained from

covariance analysis. The more nearly

par-allel their growths, the more the

individ-uals maintain their own respective positions

within the group. Thus, the reduction in

residual variance by use of covariance

anal-ysis indicates how well an individual should

As expected, the multiple correlation

coeffi-cient was a little higher for vital capacity with

height and weight, if the relationship of height

and weight was not constrained to Dubois and

Dubols’ formula.

maintain his relative position. This is

appli-cable only to the serial examination of

pa-tients. The variation on successive tests to

be expected from the calculated growth

in-crement is the standard deviation obtained

from the covariance analysis and not that

from the ordinary regression analysis. As

an example, if a subject’s vital capacity

is 10% below that predicted from his height

on one occasion, on the next occasion the

subject’s vital capacity would be expected

to be 10% below that predicted from his

new height, with some variation which can

be estimated by the SD from covariance

analysis (6.4% for boys). This is more

pre-cise than would be obtained from ordinary

regression and so enhances the perception

of significant deviation from normal growth.

By comparison of the residual variances

from the ordinary regressions and from

co-variance analysis one can see that about

three-fourths of the variance obtained from

the ordinary regression is removed by

al-lowing for a quality inherent in the

mdi-vidual. This remarkable reduction occurred

despite the relatively narrow limits of

nor-mality for this test (compared to some of

the other tests). For the FRC the

reduc-tion, about 50%, though not as striking as

that with the vital capacity, is still helpful

(13)

GIRLS FRC (ML)

4000

3500.

3000

2500

2000

1500

‘-.., ,

‘-,

.

1000

5O0

100

I I I I

110 120 130 140

HEIGHT IN CM. 174

I I

150 160 170 180 190

FIG. 6. The functional residual capacity in relation to height (girls) on logarithmic scales. Points con-nected by a solid line are from the same subject. The dashed lines indicate the calculated regression

line and two standard deviations on either side.

The dimensionally adjusted exponents

from the various regression equations

(Table IV) are informative about the

growth of the lungs. These values show

that in this age period the lungs grow as

the body does and that the independent

variables (age, height, sitting height,

weight, surface area, and biacromial width)

appear to each reflect the same body growth.

This point is confirmed by the relatively

small decreases in residual variance

re-sulting from the use of more than one of

these independent variables (Tables I and

II) to predict the lung volumes. Age,

though one dimensional in nature, does

not conform as well as the other factors.

This is not surprising since the body

growth is not a simple function of age.

The dimensionally adjusted ratios of lung

volume to age are also different for boys

and girls. This reflects tile different body

growth of the two sexes.

From further examination of Table IV

three additional facts become evident. First,

the size of the adjusted exponents for the

relationship of FRC to height in girls is

ap-preciably lower than for FRC to height in

boys and VC to height in boys and girls.

This does not mean that the values of FRC

are lower in girls than boys of the same

size (which they are) but that the

incre-ment of log FRC per increment of log body

size is less than for the other groups. The

reason for this is not clear. Secondly, for

all groups the values of the adjusted sitting

height exponents are lower than those of

the other physical measurements. This

oc-curs because the sitting height to total

height ratio changes with increasing age.

(14)

mdi-SUPPLEMENT 175

cate functional growth than does sitting

height. Thirdly, there is a difference

be-tween the sexes in the adjusted exponents

for age. This results from the smaller body

growth rate for girls than boys, and the

lung volumes reflect the body size.

The expiratory reserve volume can be

predicted from the predicted vital capacity.

In the entire age range it was about 32%

of the vital capacity, with some change in

this ratio as height increases. We feel that

a few “normal” breaths preceding the vital

capacity maneuver gave only a rough

indi-cation of end-tidal resting point and

intro-duced error in the expiratory reserve

vol-ume measurement. For this reason more

elaborate analysis was not done. It is

in-teresting that despite much variability,

in-crease in the ratio of expiratory reserve to

vital capacity with increasing age, though

not large is statistically significant.

Formulas for predicting the vital

capac-ity and functional residual capacity using

different single independent variables or

combinations of independent variables can

be obtained from the tables. From the

pre-ceding discussion it is evident that we feel

height alone is a suitable choice for routine

use. The formulas for using this

independ-ent variable after transformations of the

data in Tables I and II are as follows

(vol-umes in milliliters, height in centimeters):

VC (boys) = 2.157 X 10 X ht28’

VC (girls) = 1.858 X 10 X ht282

FRC (boys) = 7.312 X 10 X ht293

FRC (girls) = 4.781 X 10 X hr254

SUMMARY

A three-year longitudinal study of a

va-riety of lung function tests in 147 normal

children has been carried out to permit

better separation of growth effects (by

co-variance analysis) from individual

varia-tion, to supply information not previously

available, and to permit study of the

inter-relationships of the tests in normal subjects.

In this, the first of a series of papers, we

have presented the results of the study of

lung volumes. Height is the best single

in-dicator of physical size for predicting

nor-mality. Comparison of residual variances

indicates that the use of multiple

independ-ent variables offers little advantage.

Although there is reason to believe that

the lung volumes do not increase in a

sim-ple exponential relationship to height after

birth, after 5 years of age the lung volumes

do increase as approximately the cube of

height. When the values of the exponents

obtained from regression analyses of the

lung volumes on different independent

vari-ables are adjusted by the dimensional

re-lationships of the variables, several points

become evident. Among them are: (1) the

various independent variables (except

sit-ting height) are all reflecting the same

gen-eral body growth; (2) the exponents for the

FRC in girls are less than those for vital

capacity in boys or girls and less than the

FRC in boys; (3) there is a difference

be-tween boys and girls in the exponent for

age. The latter only reflects the relatively

smaller body growth of girls for each age

increment.

Analyses of covariance made possible by

the longitudinal studies indicate that about

three-fourths of the residual variance

ob-tained from the ordinary regression of log

vital capacity on log height (and one-half

of that of log FRC on log height) is due to

a quality inherent in the individual.

Knowl-edge of this factor permits future estimates

of a person’s lung volume with greater

pre-cision.

REFERENCES

1. Handbook of Respiration, National Academy of Sciences and National Research Council. pp. 388-389, Philadelphia: W. B. Saunders,

1958.

2. DeMuth, C. R., Howatt, W. F., and Hill, B.:

The growth of lung function, Part V. Flow

rates, PEDIATRICS, 35:200, 1965.

3. Handbook of Respiration, National Academy

of Sciences and National Research Council, p. 2. Philadelphia: W. B. Saunders, 1958.

4. DeMuth, C. R., and Howatt, W. F.: The

growth of lung function, Part III. Pulmo-nary (liffusion. PEDIATRICS, 35:185, 1965.

5. Dixon, W. J., and Massey, F. J.: Introduction

(15)

and 12, New York: McGraw Hill, 1957.

6. Nelson, W. E.: Textbook of Pediatrics, 7th

ed., pp. 52-55, Philadelphia: W. B.

Saun-ders, 1959.

7. Engstrom, I., Karlberg, P., and Kraepelien, S.:

Respiratory studies in children. I. Lung

volumes in healthy children, 6 to 14 years

of age. Acta Pediatrica, 45:277, 1956.

8. Helliesen, P. J., Cook, C. D., Friedlander, L.,

and Agathon, S. Studies of respiratory

phys-iology in children. I. Mechanics of

respira-tion and lung volumes in 85 normal children

5 to 17 years of age. J. Pediat., 22:80, 1958.

9. Cook, C. D., and Hamann, J. F.: Relation of

lung volumes to height in healthy persons between the ages of 5 and 38 years. J.

Pediatrics, 59:710, 1961.

10. Cherniak, R. M.: Ventilatory function in chil-dren. Canad. Med. Ass. J., 87:80, 1962. 11. Bernstein, L., Fragge, R. C., Gueron, M.,

Kreindler, L., and Ghory, J. E.: Pulmonary

function in children. I. Determination of

norms. J. Allergy, 30:514, 1959.

12. Howatt, W. F., and DeMuth, C. R.: The

growth of lung function, Part II.

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1965;35;162

Pediatrics

George R. DeMuth, William F. Howatt and Bruce M. Hill

I. LUNG VOLUMES

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I. LUNG VOLUMES

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