RESISTANCE OF THE TOTAL RESPIRATORY SYSTEM IN HEALTHY INFANTS AND INFANTS WITH BRONCHIOLITIS

(1)

(Received October 7, accepted November 15, 1968.)

This work was supported by Grant # 1-RO1HD-01392 U.S. Public Health Service, National Institute

of Child Health and Human Development, and NIH General Research Support Grant 64-FR05482-O1.

ADDRESS: (M.E.B.W.) Pulmonary Function Laboratory, Children’s Hospital Medical Center, 300 Long-wood Avenue, Boston, Massachusetts 02115.

PEDIATRICS, Vol. 43, No. 4, Part I, April 1969

495

RESISTANCE

OF

THE

TOTAL

RESPIRATORY

SYSTEM

IN

HEALTHY

INFANTS

AND

INFANTS

WITH

BRONCHIOLITIS

Mary Ellen B. Wohi, M.D., Luisa C. Stigol, M.D., and Jere Mead, M.D.

From the Department of Medicine, Children’s Hospital Medical Center, The Boston Hospital

for Women, Lying-in Division, and the Department of Physiology, Harvard School of Public Health, Boston

ABSTRACT. We have applied the forced oscilla-tory technique of DuBois to measure the resistance of the respiratory system in infants from the

new-born period to the age of 15 months. We have

com-piled normal data in this age group and related

conductance to body length. Twenty infants with bronchiolitis were studied during the acute phase of their disease, and 10 were followed for periods

up to 11 months. We found both inspiratory and

expiratory resistance to be elevated. In all infants

we found expiratory resistance to be greater than inspiratory resistance and suggest that this may be

due to dynamic narrowing of the airways on

ex-piration. Follow-up studies revealed that three

pa-tients had evidence of airway obstruction even

when “well.” PediatrIcs, 43:495, 1969, BRONCHIO-LITIS, OBSTRUCTIVE DISEASE OF AIRWAYS, MECHANICS

OF BREATHING, RESISTANCE OF RESPIRATORY SYSTEM,

PULMONARY FUNCTION TESTS IN CHILDREN, NEW-BORN INFANTS.

rF

ECHNIQUE5 for the measurement of

air-way obstruction have long been

avail-able for older children and adults. These

are based either on a direct measurement of

airway resistance or on a measurement of

expiratory flow, such as the percent vital

ca-pacity expired in one second or the peak

expiratory flow rate. The latter indirect

measurements of flow resistance are

conve-nient and easily repeated, but they require

cooperation on the part of the patient and

have not generally been applicable to

chil-dren less than three years of age. It is

desir-able to have a technique for the assessment

of airway obstruction in infants and young

children which would allow repeated

mea-surements to be made in the same patient

in the same way that the timed vital

capac-ity (or its equivalent) can be used in adult

patients. Therefore, the technique should

not require the use of sedation or the

pas-sage of an esophageal balloon.

The purposes of the present study were

to develop for use in infants the technique

of forced oscillations originally described

by DuBois, et al.’ to study the resistance of

the total respiratory system, to apply this

technique to newborn and older infants,

and to study alterations in resistance in

bronchiolitis. We have established values

for inspiratory and expiratory resistance in

normal newborn and older infants. In

in-fants with bronchiolitis, we found expiratory

resistance to be markedly elevated, whereas

inspiratory resistance was only slightly

ele-vated. These findings are in contrast to

those of Krieger,2 we shall attempt to

ex-plain this discrepancy.

MATERIALS AND METHODS

In this report resistance will be considered

to be the resistance of the total respiratory

system while the subject is breathing through

his nose; it includes the flow-resistance of

the chest wall, the lung tissue, and the

air-ways, including the nose. Pulmonary

resist-ance will be considered to be the resistance

of the lung tissue and airways, including the

nose unless it is specified that the subject is

breathing through his mouth.

If a sine wave of pressure is applied to the

(2)

I

namely its resonant frequency, the pressures

required to overcome the elastic and inertial

impedances of the respiratory system will be

equal and opposite,1 and all of the applied

pressure is dissipated in overcoming

flow-re-sistance. Forced oscillations at this

fre-quencv can be superimposed upon the

nor-mal quiet breathing pattern and the ratio of

pressure changes to the changes in flow

am-plitude can be used to measure

flow-resis-tance. Mead3 and Ferris, et al. applied

forced oscillations to the respiratory system

by producing changes in pressure within a

body chamber in which the subject sat with

his head outside. Flow was measured by

means of a mask which surrounded the

face. We have modified this technique for

infants. The mask and chamber are

illus-trated in Figures 1-3. The mask is made of

a strip of polyvinyl foam* which surrounds

the face and is held in place across the

back of the head by a strip of rubber dental

dam. The front of the mask is made of clear

lucite in which is mounted a piece of #400

Monel screent covering an opening 2.0 cm

in diameter. The foam shell can be put on

without the lucite face plate, and, before

fit-#{176}Rogers Foam Corporation, 114 Central Street,

Somerville, Massachusetts.

f Newark \Vire and Cloth Company, 351 Verona

Avenue, Newark, New Jersey.

ting the face plate, the child can be

quieted. Flow is measured as the pressure

difference from the inside of the mask to

at-mosphere. The dead space of the mask

would be large but for the fact that air is

sucked through the mask at a constant rate

which exceeds the infant’s peak inspiratory

flow. This “bias” flow of 0.31 per second is

produced by a vacuum pumps and causes a

constant flow signal upon which the

respi-ratory variations are superimposed. An

elec-trical signal equal to that caused by the

bias flow is subtracted so that the

respira-tory variations are around an artificially

produced zero flow baseline.

The forced oscillations are produced by

two pairs of untuned loud speakers which

act as a pump and are mounted in the base

of a chamber. Each pair is arranged in

se-ries and driven by an audiogeneratoril and

an audioamplifier.lf Figure 3 is a diagram

of the speakers. The infant lies supine on a

Catalogue No. XX6000000. Millipore Company, Ashby Road, Bedford, Massachusetts.

§AR-I 12 inch woofers. Acoustic Research

Com-pany, 24 Thorndike Street, Cambridge, Massachu-setts.

Model AC-9A, The Heath Company, Benton

Harbor, Michigan.

IfDynakit, Mark III, Dyna Company, Inc., 3912

Powelton Avenue, Philadelphia, Pennsylvania.

Fic. 1. The chamber in place above the loudspeakers. The series arrangement of the loudspeakers

in-creases the pressure produced by the pump and the parallel arrangement increases the capacity of the

(3)

if

0

F

FIG. 2. Close-up of the mask and neck seal. The pressure tubing in the foreground is used to measure flow and pressure across the total respiratory system and is inserted through the foam shell after it is

positioned. The tubing to the vacuum pump for the “bias flow” is seen within the mask. A variety of

neck plates were used, depending on the size of the infant. The chamber was not air tight and the seal at the neck was only good enough to maintain since wave changes in pressure within the chamber.

platform above the loudspeakers, and a

plastic dome is placed over the body of the

infant thus forming the chamber.# The

seal at the neck and above the

loud-speakers is not air tight but is adequate

to maintain undistorted sine wave changes

in pressure within the chamber. The

in-fant’s head is stabilized by a pillow of small

polystyrene spheres within a balloons which

hardens, conforming to the contours of the

head, when a vacuum is applied to the

bal-loon.

This fixation of the head is particularly

important since movement within the mask

produces flow in and out of the mask

unre-lated to flow from the airway. We tested for

the absence of flow oscillation by observing

flow when the infant closed his glottis. If

flow oscillations continued during glottic

closure, the head was held or repositioned

# J. H. Emerson Company, 22 Cottage Park Ave-nue, Cambridge, Massachusetts.

until such oscillations were less than 10% of

those with the glottis open.

The pressure difference across the total

respiratory system (i.e., the pressure within

the chamber minus the pressure within the

mask) was measured by a pressure

trans-ducer.#{176}#{176}The pressure across the

pneumo-tachograph screen which was linearly

re-lated to flow was measured by a pressure

transducerff and electrically integratedfl to

give volume. Flow, pressure, and volume

were recorded oscillographically. Tidal

vol-ume and respiratory frequency were

re-corded during quiet breathing and minute

volume was computed.

-

Forced oscillations, applied to the

respi-#{176}#{176}Sanborn #268B, Hewlett-Packard Company,

Middlesex Turnpike, Burlington, Massachusetts.

ff Sanborn #270, Hewlett-Packard Company,

Middlesex Turnpike, Burlington, Massachusetts. U Integrating Preamplifier Sanborn 350-3700,

Hewlett-Packard Company, Middlesex Turnpike,

(4)

FIG. 3. Diagram of the speakers and connections.

ratory system at frequencies ranging from 3

to 7 cps, did not appear to influence the

pattern

of respiration. At the resonant

fre-quency, flow and pressure are in phase and

there is no “looping” when flow is displayed

against pressure on an oscifioscope. This

condition was used to select the resonant

frequency. Oscillographic tracings of flow

and pressure at the resonant frequency

have relative amplitudes which express

flow-resistance of the respiratory system

(Rrs = Ply). A typical tracing is shown in

Figure 4. At other than resonant frequency,

pressure and flow are out of phase and

their relative amplitudes no longer express

flow-resistance. At two points during each

cycle, namely at the flow extremes,

acceler-ations are zero and elastic pressure

differ-ences are minimal. Accordingly, the

pres-sure differences between such points are

solely flow-resistive. By relating the

pres-sure differences between the flow extremes

to flow amplitudes, resistances can be

mea-sured at other than resonant frequencies.

Resistances were calculated by this method

at cycling frequencies ranging from 3 to 7

cps, although the resonant frequency for

most infants lay between 3 and 5 cps.

Twenty-eight healthy 3- to 4-day-old

in-fants were studied, and 29 studies were

car-ried out on normal infants ranging in age

from 1 to 15 months. All had been fed 1

to 2 hours beforehand and were given

sugar nipples to suck during the study.

Only those infants who were quiet and

breathed regularly have been included in

the normal data. The newborn and young

infants were usually but not necessarily

asleep; a number of the older infants were

awake but quiet.

In five of the newborn infants,

pulmo-nary flow-resistance was also measured.

Pleural pressure was estimated with an

eso-phageal balloon (5 cm in length, 16 mm in

perimeter) attached to #160 polyethylene

tubing. The pressure difference between the

esophagus and the mask Peso - Pinask

repre-sents transpulmonary pressure, and

pulmo-nary resistance during forced oscillation was

calculated in the same way as for the total

respiratory system.

Inspiratory and expiratory pulmonary

flow resistances were also calculated by the

method of Neergard and Wirz.6 In this

method the elastic component of pressure

§ §These dimensions are recommended by Dr.

(5)

ARTICLES

mask).

at each instant during the cycle is estimated

from simultaneous measurements of lung

volume change and separate estimates of

pulmonary compliance. Pulmonary

compli-ance is defined as the ratio of tidal volume

to the change in transpulmonary pressure

between the extremes of tidal volume and

points of zero air flow. The component of

pressure related to flow-resistance is

cal-culated by subtracting this estimate of

elas-tic pressure from transpulmonary pressure.

In three infants measurements of resistances

by the technique of forced oscillations and

by the method of Neergaard and Wirz1

were carried out on the same breaths. Two

infants were studied in the lateral position

to avoid pressure artifacts such as are seen

in adults in the supine position7 and

mea-surements of forced oscillatory resistance

and resistance by the method of Neergaard

and Wirz6 were carried out on consecutive

breaths.

Twenty hospitalized infants with

bron-chiolitis were also studied. These infants

ranged in age from 1 to 17 months and all

had an acute onset of respiratory disease.

Six had had a previous episode of

bron-chiolitis or pneumonia. The remainder had

no previous evidence of lower respiratory

disease. All had radiologic evidence of

hy-perinflation and ausculatory evidence of

wheezes, rhonchi, or rales on admission.

Al-though five infants developed radiologic

evidence of infiltrates or atelectasis,

pneu-monia was not the primary clinical

diag-nosis.

To minimize the contribution of upper

airway obstruction, all infants with

bron-chiolitis were studied following

nasopha-ryngeal suctioning and administration of

Volume,mI

I

.3 4:

:: ::t

: : :

.

: :

Flow,

L

/sec

:

Pese,

2.0

[

Time

Li I sec

FIG. 4. A typical tracing. Flow is represented as respiratory flow. The pressure measured across the pneumotachograph is proportional to respiratory flow plus the “bias flow” of 0.3 1/second. An electronic

signal equivalent to 0.3 1/second is subtracted and only respiratory flow is recorded and integrated to

give volume. The arrow on the flow tracing shows a brief period of glottic closure. Pressure is the

(6)

Case Sex Age Weight (kg) Height (cm) Forced Oscillatory (cm HsO/l/sec) Minute Ventilation (mi/mm) Tidal Respiratory Frequency Volume (ml) mm) inspiration Expiration 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 a* b C 31 32 33 a b 34 35 36 37 38 39 40 41 42 43 44 45 a b 46 47 48 49 50 51 52 53 M F F M M F M M F F M F M M M F F F F F F M M M F F M M F F M F F M M M F F M F M F 11 F F M M F M M F F M 3 da 3 da 4da 3 da 3 da 3 da 3 da 11 da 3 da 3 da 5da 3 da 3 da 4 da 3 da 4 da 4 da 4 da 3da 4 da 3 da 3 da 3 da 3 da 3 da 3 da 3 da 3 da 43 wk l6wk 20wk 27 wk 27 wk 45 wk l2wk 23 wk l5wk 14 wk 32 wk 44 wk 29 wk 45 wk 60 wk 56 wk 40 wk 56 wk 40 wk lOwk l6wk 23 wk 24 wk l6wk l6wk l7wk 6 wk 23 wk 57wk 3.40 3.08 2.98 3.40 2.68 2.79 2.79 3.49 2.97 4.38 3.18 3.20 3.04 3.25 4.15 3.10 3.56 2.89 3.17 2.91 3.08 3.23 3.07 3.62 2.97 3.88 3.18 3.42 10.00 6.20 6.82 7.47 7.88 7.92 6.27 7.65 5.95 5.76 7.37 8.37 8.05 10.19 12.30 11.80 10.70 10.00 4.99 5.76 7.34 7.06 6.39 5.87 6.48 3.32 6.69 10.45 51 49.8 50 52 47.3 48 48 50.2 48.2 54.5 51.4 49.5 48.3 49.5 56 49 52 46.5 50.5 48 49 51.5 51 51 49 54.5 52 53 71 63 66 70 72 71 60 67 63 60 70 73 70 77.5 81 78 80.5 80 61 65 67 70 63 60 68 51 70 73.5 72 129 103 48 58 37 72 67 50 112 66 55 52 41 103 105 98 79 61 64 50 60 50 60 42 60 72 30 60 22 34 35 58 51 33 33 87 65 24 38 88 50 44 53 38 53 58 72 35 38 24 93 80 135 156 62 54 48 108 81 66 143 87 84 60 128 41 140 300 99 101 74 95 57 67 55 151 101 47 49 43 65 43 39 85 32 34 39 40 44 49 25 43 49 59 24 40 42 33 39 45 41 67 49 107 38 47 22 582 656 645 572 636 897 674 518 677 875 695 957 758 586 776 704 653 498 574 548 426 625 758 1,335 989 922 570 1,351 3,730 2,286 1,088 2,022 1,362 2,231 1,431 2,030 1,998 2,843 1,727 3,296 2,147 1,332 1,838 1,508 903 1,264 919 1,511 4,474 14 12 14 14 12 13 14 16 14 19 17 15 12 12 18 20 18 26 13 16 13 15 15 21 15 20 17 18 73 56 39 67 32 50 36 51 69 81 79 94 83 22 45 83 32 40 25 54 112 41 57 46 41 54 67 49 33 50 47 42 64 61 47 44 86 36 25 43 35 32 40 50 64 66 47 33 74 51 41 28 30 43 45 40 40 29 35 22 35 26 61 41 45 29 32 37 28 40

* The letters represent repeated studies on the same infant.

TABLE I

(7)

(‘a 0

. .

0

.

S

.

S E

C.,

.C.j

a’

(1)

-J

a)

C., C 0

C.,

0 C 0

(-)

S S

S

S S

S

S S

S

S S

S

y’L16+.03x (r:.549, p<.0I)

ARTICLES

.

3 3 -4,

Length, cm xIO

FIG. 5. Conductance (the inverse of resistance) is plotted against length cubed, for newborn and older infants. Dots represent values for individual

infants.

one-fourth percent phenylephrine HC1 nose

drops.

RESULTS IN HEALTHY INFANTS

Data on healthy newborn and older

in-fants are presented in Table I. In some

infants the inspiratory phase of respiration

was too rapid for good measurements of

inspiratory resistance, and none have been

reported for these infants. Tidal volumes,

frequency, and minute ventilation were

ob-tained during quiet breathing before or

after oscillation. In some infants these data

were not obtained. In the newborn group,

mean inspiratory resistance ±1 S.D. was

69 ± 25 cm H2O/l/second and mean

expi-ratory resistance ± 1 S.D. was 97 ± 52

cm H2O/l/second. For infants from the age

of 1 to 15 months, the mean inspiratory and

expiratory resistances were 46 ± 17 cm H2O

/1/second. In Figure 5, expiratory

conduc-tance (the reciprocal of resistance) is

plot-ted against body length cubed. We found

a significant relationship between

conduc-tance and this index of body size.

In five newborn infants we partitioned

total respiratory system resistance into the

resistance of the chest wall and the

resist-ance of lung tissue and airways. Chest wall

resistance is presented as a percent of total

respiratory system resistance in Table II.

To compare the data in newborn infants

with those obtained by a similar technique

in adults,8 we utilized the finding of

Polgar9 that nasal resistance comprises 26%

of the pulmonary resistance in infants and

calculated chest wall resistance as a percent

of total respiratory system resistance for

“mouth-breathing” infants. We estimated

the contribution of the chest wall to total

respiratory resistance to be about the same

in infants and adults. We have assumed this

to be true for all our infants and have

esti-mated pulmonary resistance by subtracting

an estimate of chest wall resistance from

total respiratory resistance. In this way we

were able to compare our results with those

of other investigators who, using the

method of Neergard and Wirz,#{176}have

mea-sured pulmonary resistance in

nose-breath-ing infants. This comparison is made in

(8)

pulmo-TABLE II

RESISTANCE OF THE CHEST WALL AS PERCENT OF RESISTANCE OF TOTAL RESPIRATORY SYSTEM

.

Subject inspirationrn-i

‘/o)

Expiration

ei

/c

Adults-S mouthbreathing Newborns-S

nosebreathing Newborns*

“mouthbreathing”

34.8 (19-46)

25 (14-40) 28 (18-47)

38.6 (24-04)

28 (21-39) 36 (27-46)

Number of observations and ranges of values are given inparentheses.

* Calculated on the assumption that nasal resistance is 26% of the pulmonary resistance.8

nary resistance in newborn infants were

sig-nificantly higher (p < .01) than the values

obtained by Cook,1#{176}Swyer,11 and Burnard.13

In five infants we measured resistance by

the method of Neergaard and Wirz6 and

found that our values of resistance were also

significantly higher than the values obtained

by Cook,10 Swyer, and Burnard” but not

significantly different from those obtained

by Karlberg’2 and by Polgar.9 In healthy

older infants our estimated values for

ex-piratory resistance were not significantly

different from those obtained by Krieger,14

although her values for inspiratory

resist-ance are somewhat lower.

We calculated pulmonary resistance

ob-tained by the method of Neergaard and

WirZ6 and by the technique of forced

oscil-lations on either the same breaths or closely

adjoined breaths in the same period of

quiet breathing in five newborn infants.

This data is presented in Table IV.

Al-though the mean results do not differ

signif-icantly, in all infants inspiratory resistance

was slightly lower when measured by the

technique of Neergaard and Wirz,6 and in

three infants expiratory resistance was

lower. In 4 of the 10 measurements this

difference was significant (p < .01).

Total respiratory resistance on expiration

obtained in 13 normal infants at

frequen-cies from 3 to 7 cps is given in Figure 6. We

could not demonstrate any frequency

de-pendence over this limited frequency range.

RESULTS IN BRONCHIOLITIS

The results of our studies on 20 patients

admitted to the hospital with the diagnosis

of bronchiolitis are presented in Table V.

TABLE III

VALUES OF RESISTANCE IN NOSEBREATHING INFANTS

Study

Number of

Observa-tions

Pulmonary Resistance (cm H,O/l/sec)

Total Respiratory Remskince (cm H,.O/l/sec)

Mean inspiration Expiration Inspiration Expiration

Newborns

Cook, et al.’#{176}

Swyer, et d.

Karlberg and KochlI*

Polgar and Kong9

Burnard, et al.” Present studyt Infants

Krieger’4

Present studyt

18

9 20

5

11 29

24

29

29 ± 12.9

26 ± 6.5 38.5 ± 25.2

47.5±5.6

29 ± 20

25 ±7.7 52

22± 17 34

36 ±7.8 70

37 ±29 83

69 ± 25

46 ± 17

97 ± 52

46 ± 17

* Includes only infants 20-45 hours old.

t

Calculated assuming contribution of the chest Wall to be 25% of total resistance for inspiration and 28% for

(9)

TABLE IV

PULMONARY RESISTANCE CALCULATED BY THE METHOD OF NEERGAARD AND WIRz AND BY THE METHOD OF

FORCED OSCILLATIONS (5-6 CPS)

* Measurements made on same breaths; patient supine. t Measurements made on consecutive groups of breaths; patient in lateral recumbent position.

150

100

50

3.25 4.5 5.7 6.6

Frequency, cycles /sec.

7.5

FIG. 6. Expiratory resistance in healthy newborns and infants at a variety of

frequencies. Data on each individual are joined by a line.

ARTICLES

These studies are summarized and

com-pared to studies on healthy infants in Table

VI. Respiratory frequency was increased

and tidal volume decreased in patients with

bronchiolitis. Minute ventilation was

com-parable to that of healthy infants.

The mean value for inspiratory resistance

in patients with bronchiolitis was 93 ± 75

cm H20/l/second compared to 46 ± 17

cm H2O/1/second in healthy infants of the

same age. The increase in inspiratory

resist-ance was significant (p < .005). The mean

value for expiratory resistance was 152 ±

57 cm H2O/1/second which was highly

significant when compared to normal values

of 46 ± 17 cm H2O/l/second (p < .001).

Values for inspiratory and expiratory

resist-ance are presented graphically in Figure

7. In all instances where values for both

inspiration and expiration are available,

ex-piratory resistance was found to be higher

than inspiratory resistance. Abnormal

in-fants were not studied over a wide enough

range of frequencies to demonstrate

pres-ence or absence of frequency dependence.

We studied 14 infants on more than one

occasion. Results from these infants are

pre-sented in Figure 8. Eleven infants were

studied on several occasions in the first

week of hospitalization. Values for both

in-U

a,

‘I)

0

N

E U

a)

C., C 0

U) U) a)

infant

Resistance (cm H,O/I/sec) Method of Neergaard

and Wirz

Resistance (cm 11,0/1/sec) Method of Forced

Oscillation inspiration Expiration inspiration Expiration

18’ 19t 0t I’ 7’

Mean

57 40

55

IS es

61

30 53

45

79

5

9

75 53

56

148

38

74

189

5

59

88

01

90

spiratory resistance and expiratory

resist-ance returned to normal in five infants,

and the marked difference between

resis-tance during inspiration and during

expira-tion decreased within the first week in

seven infants. This decrease in resistance

paralleled clinical improvement in most

in-stances. In one patient (VN), there was

marked clinical improvement but marked

increase in expiratory resistance.

Seven patients were studied after

inter-vals of 2 months or longer from the time of

(10)

normal values of resistance. However, two

infants

(J

Ga and SM

)

still had elevated

resistances for both inspiration and

expira-tion. Another patient

(

MF

),

who has

be-come too big to study in the present

ap-paratus, has been followed and has had

continued evidence of airway obstruction.

DISCUSSION

We cannot explain why our values for

pulmonary resistance are higher than those

reported by others (Table III ). Since this is

also true for our values obtained directly

with an esophageal balloon during

sponta-neous breathing, the differences cannot be

accounted for either by incorrect estimates

of chest wall resistance or by difference in

frequency. Since the tidal volumes and

res-piratory frequencies are similar to those

reported by other investigators, it is

un-likely that our infants were breathing at

higher flow rates.

Since resistance, particularly during nose

breathing, is nonlinear and increases with

flow, one would expect that resistance

measured by the technique of forced

oscil-lations would be somewhat higher than

re-sistance measured by the method of

Neer-gaard and Wirz.6 Although the differences

are not statistically significant for the

group, we did find oscillatory resistance to

be higher in 8 of 10 measurements made on

the five infants in whom we compared the

two techniques. All the infants had a nipple

in place and a possible, but unproven,

hy-pothesis is that sucking motions contribute

to the increased resistance.

According to Otis,

et aL,15

frequency

de-pendence of resistance is to be expected if

the mechanical time-constants of the

sep-arate pathways within lungs are not equal.

We found no frequency dependence over a

narrow range of frequencies (3 to 7 cps),

which suggests that the time constant

dis-crepancies in normal infants’ lungs must be

small and is in contrast to the findings of

TABLE V

DATA ON INFANTS WITH BRONCHI0LITIS

(11)

ARTICLES 505

TABLE VI

CoMPARISON OF HEALTHY INFANTS AND INFANTS WITh BRONCIIIOLITIS

Subjects

R1

(cm H,O/l/sec)

RE

(cm H2O/l/sec)

Respiratory Frequency (breoi.hs/min)

Minute

Ventilation

(mi/minim2)

Insp/Exp tune

Normals 46 ± 17

Bronchiolitis 93 ± 75

p <.005

46 ± 17 152 ± 57*

<.001

37 50 <.001

5174 5863

.75 .68

.001

* This mean does not include values for two patients which were over 350 cm HsO/l/sec and, therefore, could not be accurately calculated.

frequency dependence of compliance in

normal children reported by Helliesen,

et

al.’#{176}Grimby, et al.17 have recently found

frequency dependence of resistance in

adult patients with chronic obstructive lung

disease, but the percent changes between 3

and 7 cps were small compared to the

strik-ing changes in pulmonary compliance

be-tween quasi-static conditions and the

fre-quencies of spontaneous respiration. It is

entirely possible that, despite the finding of

frequency dependence of compliance, the

children studied by Helliesen,

et

al.#{176}would

not have demonstrated frequency

depen-dence of resistance, and our findings are

probably not in conflict.

In the newborn group we observed

ex-piratory resistance to be higher than

inspi-ratory resistance. Although this greater

re-sistance during expiration may possibly

reflect systematic changes in upper airway

(e.g., laryngeal or pharyngeal) resistance,

it seems somewhat more likely that it is

caused by dynamic compression of

intra-thoracic airways. In adult lungs dynamic

compression of intrathoracic airways is

fa-vored when lung volume, and hence lung

static recoil, are reduced. For example,

vol-untary breathing at volumes approaching

residual volume invariably is associated

with dynamic compression. The high

com-pliance of the newborn chest wall’82#{176}

prob-ably allows a less subatmospheric pleural

pressure at end expiration. This in turn

would result in a reduced lung volume and

some predisposition to dynamic

compres-sion.

Before comparing Krieger’s2 and our

re-sults in infants with bronchiolitis, it should

be noted that substantial differences exist

between the two groups of patients. In

gen-eral, our sick infants were younger and

smaller, breathed less rapidly, and took

rel-atively more time during expiration. Real

differences in respiratory mechanics may

relate to these differences. However, other

differences must relate to the fact that we

were measuring different things. Our

mea-surement of resistance is insensitive to the

shape of the static volume-pressure

charac-teristic of the lung. As Krieger2 points out,

the method of Neergaard and Wirz,6

which she used, depends on the assumption

of constant pulmonary compliance in the

tidal volume range. Curvilinearity of the

static volume-pressure characteristic in the

sense seen at high lung volumes

(

i.e.,

corn-pliance decreasing as lung volume

in-creases) leads to underestimation of

in-spiratory and overestimation of expiratory

resistance. To account for Krieger’s2 finding

of increased inspiratory and decreased

ex-piratory resistance, the curvilinearity would

have to be in the opposite sign, i.e.,

compli-ance would have to increase with lung

vol-ume. As she points out, this would be the

case of obstructed airways opened during

inspiration and closed at the same volume

during expiration.

Ordinarily, when put through a

suf-ficiently large volume excursion, lungs

ex-hibit static hysteresis, i.e., the static

volume-pressure characteristics during deflation

(12)

400

C,

a,

300

0

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I

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a, C,

C

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U, a)

506 RESPIRATORY RESISTANCE

pressures at a given volume on deflation

are less than pressures at the same

vol-ume on inflation. This is, at least in part, to

be expected, since opening pressures for air

spaces would be greater than closing

pres-sures and more air spaces would remain

open at the same volume during deflation.

In contrast, it is reasonable to assume that

the opening and closing pressures of

air-ways may be similar. If this is the case and

other sources of static hysteresis are small,

obstructed airways would open and close at

nearly the same lung volume, and the

over-all volume-pressure characteristic would

show an increased slope as inspiration

pro-gressed and would reverse itself during

ex-piration. The static volume-pressure

charac-teristic would then have a hockey-stick

shape, with relatively little static hysteresis.

It seems likely that the hyperinflated state

of lungs during acute episodes of

bronchio-Inspiration

FIG. 7. Values for resistance on inspiration and

expiration in patients with bronchiolitis. Dots

rep-resent individual data. Values from the same

infant are joined by lines. Open circles represent

values over 350 cm HO/l/second. The line in

the shaded areas represents mean data for healthy

infants 1 to 15 months old, and the shaded area

represents ±2 S.D.

litis results from airway closure.

Further-more, a substantial number of these airways

must open with each inspiration or the air

spaces beyond would eventually become

gas-free. Thus, it seems reasonable that

compliance may increase during inspiration

and decrease during expiration. In this case

the assumption of constant compliance

would lead to underestimates of expiratory

and overestimates of inspiratory resistance.

Krieger’s2 values for the “combined

re-sistance,” i.e., the mean of inspiratory and

expiratory resistance, should be insensitive

to non-linearity of the static

volume-pres-sure characteristic of the lung, and it is

in-teresting that this value was in the normal

range. As Krieger points out, the infants

were presumably breathing at a high lung

volume where resistance would be much

less and, accordingly, the combined value

cannot be regarded as normal. It is

nev-ertheless lower than the values for

resist-ance which we found. This difference

probably does reflect real differences

be-tween the two groups of patients and is

un-related to the assumptions about

compli-ance.

Krieger explains the relatively normal

values of resistance which she found on the

basis of inequality of time constants with

low resistance pathways contributing most

to the measured resistance. An additional

possible explanation for her findings may

be that there was complete closure of

ter-minal units with air trapping. This would

tend to make the lung stiffer, but not to

in-crease resistance. An experimental model

for such disease may be the work of Nadel,

et aL,21 who produced alveolar duct closure

after barium sulfate emboli. They found

lit-tle increase in resistance and a decrease in

compliance which Krieger observed in the

Expiration bronchiolitic infants.

Our patients, however, showed a marked

increase in expiratory resistance, and

expir-atory resistance was always greater than

in-spiratory resistance. If part of the increase

in resistance resided in the intrathoracic

airways, increased resistance on expiration

(13)

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ARTICLES

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300

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Esp.ratory Resistance

o- --o Inspirotary Resistance

#{149}Exprotory Resistance >350 cmH20/L/sec. ± 2 S.D. of mean insp. and exp. R Time afrom dote of hosptahzahon

Fzc. 8. Data from infants with bronchiolitis who were studied repeatedly during and after their acute

illness. Day zero represents day of hospitalization for bronchiolitis. The shaded area represents mean

data ± 2 S.D. for healthy infants from 6 to 60 weeks of age and does not show the decrease in resistance associated with body growth (see Fig. 5).

cause the distending pressures across the

walls of airways would be less on expiration

than on inspiration, the airways would be

smaller at a given lung volume, and the

re-sistance would therefore be greater. If the

patients made forced expiratory efforts,

fur-ther “collapse” and increase on expiration

would occur. We suggest that this

mecha-nism contributes to the high expiratory

re-sistance which we observed in infants with

bronchiolitis.

If a large part of the increased expiratory

resistance is “dynamic” as we suggest,

in-spiratory resistance may be a more accurate

reflection of the state of the airways if the

obstruction is intrathoracic. Although a

number of our patients had inspiratory

re-sistances which fell within the normal

range, we found inspiratory resistance for

the group to be signfficantly elevated.

Similar considerations of “dynamic”

in-creases in resistance could occur during

in-spiration in extrathoracic obstruction. It is

interesting that many of Krieger’s2 infants

with the syndrome of bronchiolitis had

rela-tively prolonged inspirations (as manifest

by a significantly increased inspiratory/

expiratory time ratio), and “dynamic

nar-rowing” of the extrathoracic airways may

account for some of her observed increase

in inspiratory resistance.

(14)

re-508

covery indicate that, in most patients

(

seven

)

,

bronchiolitis was an acute disease

leaving no permanent alterations in

resist-ance. Two of these patients had

subse-quent episodes of bronchiolitis but, when

studied during a period of clinical

well-being, had normal resistances. Two other

patients had elevated resistances even

dur-ing symptom-free periods. A third patient

included in this study

(

MF), has had

re-peated hospitalizations for “bronchiolitis.”

The possibility exists that these patients

have an underlying and perhaps

irrevers-ible abnormality of the airways. Some of

these patients may indeed have asthma,

and it is interesting to note that in 14 of the

18 patients in whom the family history was

known, there was a family history of

ec-zema, asthma, or hay fever.

These studies suggest that the clinical

syndrome of “bronchiolitis” includes

pa-tients who have a single, self-limited

epi-sode of disease characterized by

hyperinfla-tion and increased resistance, patients who

have repeated episodes of acute airway

ob-struction but are clinically well with normal

resistance between episodes, and patients

who have repeated respiratory infections

but have abnormal resistances even when

“well.” The group of patients who have

in-creased inspiratory resistance reported by

Krieger#{176} may represent a fourth type of

al-teration in pulmonary mechanics.

These studies on patients with

bronchio-litis also illustrate the feasibility of and need

for repeated studies in infants with

obstruc-tive airway disease. The method of forced

oscillation has proven to be a convenient

method for assessing resistance and permits

repeated measurements without sedation.

REFERENCES

1. Dubois, A. B., Brody, A. W., Lewis, D. H., and Burgess, B. F., Jr.: Oscillation mechan-ics of lungs and chest in man. J. Appl. Phys-iol., 8:587, 1955.

2. Krieger, I.: Mechanics of respiration in bron-chiolitis. PznlATmcs, 33:45, 1964.

3. Mead, J.: Control of respiratory frequency. J.

AppI. Physiol., 15:325, 1960.

4. Ferris, B. G., Jr., Mead, J., and Opie, L. H.:

Partitioning of respiratory flow resistance in

man. J. Appl. Physiol., 19:653, 1964.

5. Mead, W. J., and Collins, V. P.: The principles of dilatancy applied to techniques of

radio-therapy. Amer.

J.

Roentgen., 71 :864, 1954.

6. Neergaard, K., and Wirz, K.: Ober eine

Me-thode zur Messung der Lungenelastizitat

am lebenden Menschen, insbesondere beim

Emphysem. Z. Kiln. Med., 105:35, 1927.

7. Milic-Emili, J., Mead, J., and Turner, J. M.:

Topography of esophageal pressure as a

function of posture in man. J. Appl.

Phys-iol., 19:212, 1964.

8. WohI, M. E., Gross, P., and Mead, J.:

Un-published observations.

9. Polgar, C., and Kong, C. P.: The nasal

resist-ance of newborn infants. J. Pediat., 67:557,

1965.

10. Cook, C. D., Sutherland, J. M., Segal, S.,

Cherry, R. B., Mead, J., Mcllroy, M. B., and Smith, C. A.: Studies of respiratory

physiol-ogy in the newborn infant. III.

Measure-ments of mechanics of respiration. J. Clin.

Invest., 36:440, 1957.

11. Swyer, P. R., Reiman, R. C., and Wright, J. J.:

Ventilation and ventilatory mechanics in the

newborn. J. Pediat., 56:612, 1960.

12. Karlberg, P., and Koch, C. : Respiratory studies

in newborn infants. III. Acta Paediat.

(Suppl. 135), 121, 1962.

13. Burnard, E. D., Grattan-Smith, P.,

Picton-Warlow, C. G., and Grauaug, A.: Pulmonary

insufficiency in prematurity. Aust. Paediat. J., 1:12, 1965.

14. Krieger, I.: Studies on mechanics of respiration in infancy. Amer. J. Dis. Child., 105:439, 1963.

15. Otis, A. B., McKerrow, C. B., Bartlett, R. A.,

Mead, J., Mcllroy, M. B., Selverstone, N. J.,

and Radford, E. P., Jr.: Mechanical factors

in distribution of pulmonary ventilation. J.

Appl. Physiol., 8:427, 1955.

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

and Agathon, S.: Studies of respiratory

physiology in children. 1. Mechanics of

res-piration and lung volumes in 85 normal

chil-dren 5 to 17 years of age. Pwriucs, 22:80,

1958.

17. Grimby, C., Takishima, T., Graham, W.,

Macklem, P., and Mead, J.: Frequency

de-pendence of flow-resistance in patients with

obstructive lung disease. J. Clin. Invest., in

Press.

18. Agostom, E.: Volume-pressure relationships of

the thorax and lung in the newborn. J. Appi.

Physiol., 14:909, 1959.

(15)

Volume-pres-sure relationships of lungs and thorax in

fetal, newborn and adult goats. J. Appl.

Physiol., 16:1034, 1961.

20. Richards, C. C., and Bachman, L.: Lung and

chest wall compliance of apneic paralyzed infants. J. Chin. Invest., 40:273, 1961. 21. Nadel, J. A., Colebatch, H. J. H., and Olsen,

C. B.: Localization and mechanism of

air-way constriction after barium sulphate

mi-croembohism. J. AppI. Physiol., 19:387,

1964.

Acknowledgment

The authors wish to express thanks to Dr. C. D.

Cook, Dr. E. 0. R. Reynolds, and Dr. E.

Moto-yama for their encouragement and help in the

ini-tial phases of this study; to Dr. C. A. Smith and

Dr. K. P. Reigel at the Boston Hospital for

Women, Lying-in Division, for providing space

and assistance in the studies of normal infants; and

to Mrs. Ann Chapman for her skill and care with

these studies.

A SAD STORY

READ

BY CHILDREN IN A POPULAR READER OF THE 1860’S

Children’s readers of a century ago

con-tamed lessons far different from those in our

contemporary ones. A good example of this

difference is the following story in a widely

read reader published in 1867.

PLEASE GET IT Now, BROTHER

“Hand me some water, brother, won’t you?” said

a little sick girl.

“In a minute, Bettie,” said Harry, and his little

hands went on as busy as ever with the trap he

was making. Bethe’s fevered cheek was again

pressed to the pillow, and Harry soon forgot her

request.

“Please get it now, brother,” and her voice was

very feeble. But Harry heard it and ran for the

water, and soon was holding the cup to his sister’s

lips.

“Not this, please, but some fresh and cold water

from the well,” and she turned her head languidly away.

“0, don’t be so particular! This is fresh; and I am so busy, I can not go to the well now-won’t this do?”

Bettie no longer refused, but quietly took the

cup which Harry offered her. It was the last time

she ever called upon her brother for an act of

kindness.

The next day she stood beside the River of Life,

and drank of its cool waters. Sickness and death

had passed away, and little Bethe would thirst no more.

But Harry could not be comforted. Of all who

wept over the little brown coffin, as it lay on the

table before the pulpit, there were none who shed

more bitter tears than the boy who could not for-get that he had refused the last request of his sis-ter.

Children, are you kind to one another? or are

you cross, and selfish, and fretful! Remember, the

time will come when your brother, or sister, or

playmate, will die.

Oh, how you will then remember every unkind

word, every selfish act, that gave them pain; and

then you would give-O, how gladly you would

give all you possess to take them all back.-But it will be too late!

Harry was a kind-hearted boy, and dearly loved his sister, and he did not think that she would die. But this did not take away the sting of the last act of kindness.

“Oh, mother!” he would say, “if I had only

brought that cold water for her, I could bear it; but now I can never, never ask her forgiveness, nor wait on her again!”

Think of this, children, when you are tempted to

quarrel, to be selfish, or unkind; and may the

Blessed Jesus so keep you, that you may never

have to mourn as Harry did.1

NOTED BY T.E.C., JR., M.D.

REFERENCE

1. Edwards, R., and Webb, J. R.: Analytical Third

Reader. New York: Taintor Brothers and

(16)

1969;43;495

Pediatrics

Mary Ellen B. Wohl, Luisa C. Stigol and Jere Mead

INFANTS AND INFANTS WITH BRONCHIOLITIS