Contributions of Loss of Lung Recoil and of Enhanced Airways Collapsibility to the Airflow Obstruction of Chronic Bronchitis and Emphysema

Contributions of Loss of Lung Recoil and of

Enhanced Airways Collapsibility to the Airflow

Obstruction of Chronic Bronchitis and

Emphysema

D. G. Leaver, … , A. E. Tattersfield, N. B. Pride

J Clin Invest.

1973;

52(9)

:2117-2128.

https://doi.org/10.1172/JCI107396

.

We investigated the contributions of intrinsic disease of the airways, loss of lung recoil and

enhanced airway collapsibility to the airflow obstruction of 17 patients with chronic

bronchitis and emphysema. Airways conductance at low flow (G

_aw

), maximum expiratory

flow (V

_{E, MAX}

) and static lung recoil pressure [

P

_st

(l)] were measured at different lung

volumes, and conductance-static recoil pressure and maximum flow-static recoil pressure

curves constructed. Low values of ΔG

_aw

/Δ

P

_st

(l) and V

_E

, max/Δ

P

_st

(l) were attributed to

intrinsic airways disease. Airway collapsibility was assessed by comparing G

_aw

with

upstream conductance on forced expiration and by the intercept of the maximum flow-static

recoil curve on the static recoil pressure axis (

P

_tm

¢

).

All patients had reduced G

_aw

at all volumes but in seven ΔG

_aw

/Δ

P

_st

(l) was normal. On

forced expiration, maximum flow in all patients was reduced more than could be accounted

for by loss of lung recoil. V

_{E, MAX}

/Δ

P

_st

(l) was reduced in the patients in whom ΔG

_aw

/

P

_st

(l) was low. In contrast V

_{E, MAX}

/Δ

P

_st

(l) was normal in three and only slightly reduced in

another three of the seven patients with normal ΔG

_aw

/Δ

P

_st

(l). In these patients G

_aw

greatly

exceeded upstream conductance and

P

_tm

¢

was increased.

We conclude that loss of lung recoil could account for the reduction in resting airways

dimensions in 7 of the 17 patients. Enhanced airway […]

Research Article

Find the latest version:

Contributions of Loss of Lung Recoil and of

Enhanced Airways

Collapsibility

to

the Airflow Obstruction

of

Chronic

Bronchitis and

Emphysema

D. G.

LEAvER, A.

E.

TATrERSFIELD, and

N. B. PRIDE

FromtheDepartmentof Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London,W.12.England

ABS T R AC T We investigated the contributions of

in-trinsic disease of the airways, loss of lung recoil and

enhanced airway collapsibility to the airflow obstruc-tion of 17 patients with chronic bronchitis and emphy-sema. Airways conductance at low flow (G.,), maxi-mum expiratory

flow (VE.

MAX) and static lung recoil pressure [P.,t(L)] were measured at different lung vol-umes, and

conductance-static

recoil pressure and maxi-mum flow-static recoil pressure curves constructed. Low

values of

AG.w/APa

(L) and AVc, max/AP.t (L) were attributed to intrinsic airways disease. Airway

collapsi-bilitv was assessed by comparing G.w with upstream conductance on forced expiration and by the intercept of the maximum flow-static recoil curve on the static

recoilpressure axis

(Ptm.).

All patients had reduced Gaw at all volumes but in seven

GaGw/APatP(L)

was normal. On forced expiration, maximum flow in all patients was reduced more than could be accounted for by loss of lung recoil.

AVE, MAX/

AP.1(L) was reduced in the patients in whonm AG.,/

P,. (L) was low. In contrast

AVE,

MAX/AP,t (L) was nor-mal in three and only slightly reduced in another three of the seven patients with normal

AGaw/APat (L).

In these patients

Gaw

greatly exceeded upstream

conduc-tance and Ptm' was increased.

We conclude that loss of lung recoil could account for ,he reduction in resting airways dimensions in 7 of the 17 patients. Enhanced airway collapsibility commonly contributed to reduction in maximum flow. In three patients the airflow obstruction could be entirely ac-counted for by loss of lung recoil and enhanced airway

collapsibility.

Received for publication 16

August

1972 and in revised

form26February1973.

INTRODUCTION

Pathological change in the airway wall and lumen leading to narrowing and occlusion is commonly con-sidered to be the most important abnormality in chronic

airvays obstruction. Nevertheless, it has been recog-nized for many years that in some patients loss of lung recoil and abnormal dynamic narrowingofairways must

contribute to the expiratory difficulty

(1, 2).

Recent

studies have shown that lung recoil pressure is an im-portant determinant of the forces distending theairways during quiet breathing

(3, 4),

and of the

driving

pres-sure for maximum flow on forced

expiration

(5, 6);

in

addition, it has been shown that enhanced collapsibility

of the airways will reduce maximum flow

(6).

In this paper we attempt to quantify the contributions of

patho-logical changein theairway or its lumen of loss of lung

recoil and of enhanced airway collapsibility to the air-flow obstruction of 17 patients with "chronic bronchitis and

emphysema." Studies

have been made during quiet breathing and during forced expiration, and the results

indicate that loss of recoil pressure plays an important

role in reducing airway dimensions at low flow and that

enhanced airway collapsibility contributes to the

reduc-tion in maximum expiratory flow

(VE,

MAX).'

A

prelimi-nary report has already been published

(7).

'_{Abbreviations used in this paper: FEV1, forced}

expira-tory volume in 1 s; FRC, functional residual capacity;

G.m,

total airways conductance; G., conductance of the air-ways in the S segment;

CGus,

conductance of the upstream segment; P., (L), static transpulmonary pressure; Ptm',

critical transmural pressure of flow-limiting airways; SGas

specific airways conductance; TLC, total lung capacity;

VE MAX,maximum expiratoryflow.

VE

VI

A/ j

/

/

,/,

,,.

-;"I'

,7

-FIGURE 1 Schematic isovolume pressure flow curve in mid-vital capacity. Conductanice is represented graphically by

the slope of the interrupted lines. Because the pressure-flow

relationship is curvilinear, conductance varies with the alveolar pressure applied. A represents the conductance at zero flow [in practice obtained by measuring the pressure-flow slope between zero flow and an inspiratory flow (V,)

of 0.5 liter/sI. B represents the conductance at the mini-mum alveolar pressure associated with maximum expiratory

flow (PA'). C represents the conductance at a high alveolar pressure. The reduction in conductance between B and C is accounted for entirely by increase(d dynaamic compression of large airways in the downstream segment, while con-ductance of the upstream segment is unchanged (see text).

METHODS

Airways are elastic structures whose dimensions vary with changes in lung volume and with the dyinamic forces

developed during breathing. Both these factors can be controlled by studying the relation betw-een alveolar pressure and flow over a range of pressures at a single lung volume

(8). A typical isovolume pressure-flow curve is shown in Fig. 1. On such a curve, total airways conductance (flow/

alveolar pressure) is represented graphically by the slope joining any individual pressure-flowf point to the origin, so

even at a single lung volume, conductance varies

continu-ously with the alveolar pressure applied. In this complex

situation there are two conditions under which at least some of the airway dimensions are fixed. The first is during

breath-holding, when gas flow is zero and alveolar pressure

equals atmospheric pressure. The second is at high values of alveolar pressure, where there is a plateau of expiratory

flow at the maximum value and flow becomes independent

of the driving pressure. Although on the plateau of an

iso-volume pressure-flow curve, total airw ay conductance de-creases in parallel with increases in alveolar pressure, the intrabronchial pressure measurements of Macklem and Wil-son (9) have shown that over the middle of the vital

capacity in normal men this decrease is accounted for

en-tirely by progressive dynamic compression of the largest

intrathoracic airways. Measuring

VE,

MAX therefore not _only

assesses the maximum dynamic performance of the lungs

but can also provide information about the dimensions of the smaller airways (upstream segment of Mead, Turner, Macklem, and Little (5), see below) during forced

expi-ration.

In the present patients we have examined these twopoints

on the isovolume pressure-flow curve by measuring

con-ductance close to zero flow and

VE,

MAx at a variety of lung

volumes. As shown in Fig. 1, between these two poiInts on the isovolume pressure-flow curve the pressure-flow rela-tion is curved. Although this is usually the relevant part of the curve duiring tidal breathingr, it is much more diffi-cult to analyse and we make no attempt to do so in the presentpaper.

Static dimensions of the

_airwcays:

the conductance-static recoil plot. Our aim in this study was to distinguish changes in airway size that are caused by reduction in

airway-distending forces from those that reflect a change in the airway wall or lumen itself. We use the term in-trinsic disease of the airways to describe the situation where

airway narrowing has to be ascribed to changes in the airway wallorlumen.

In intact man the relationship between airway dimensions and airway distending pressure can be approximated by plotting total airways conductance

(Ga.),

measured at low flows, against static transpulmonary pressure [P.t(L)]. Con-ductance provides a relatively sensitive measurement of the overall diameters of the tracheobronchial tree, because for laminar flow, con(luctanice is proportional to the fourth power of the radius of the airways. There is empirical evidence that P*, (L) is a useful indicator of the forces distendinig the airwx-ays during breath-holding or breathing at low flows. In man, when the relation between P.,(L) and volume is altered by strapping the chest wall, airway conductance remains closely related to P.t(L) (3, 10). Hyatt and Flath (11) found that in dogs there wvere only small differences between the diameters of intrapulmonary airways when studiedl at a giveniPst(L) in the intact lung and at the same transbronchial pressure after the lung parenchyma had been dissected away. Although these studies indicate that P.t(L) is closely related to airway dimensions, this does not necessarily mean that peribronchial pressure is identical with pleural surface pressure. A recent theoretical analysis by Mead, Takishima, and Leith (4) suggests that the forces (listending the bronchi would be exactly equiva-lent to Ps,(L) only if the specific compliance of alveoli and bronchi were equal and if there x-ere no tension in the limiting membrane of the bronchus. \We know of no direct comparisons of specific compliance of bronchi and alveoli in human lungs; it has been su-gested that in dog lungs spe-cific compliance of bronchi may be less than that of alveoli (4), althoughl other recent experiments have not shown

Normal

Gaw

/KLoss of lung recoil

}/

/ Reduced bronchial

// 'distensibility"

Pst (L)

FIGURE 2 Schematic conductance-static recoil plot. Loss of lung recoil does not affect the conductance-static recoil slope. A reduced slope indicates a reduction in the overall

a.

normal

D

/loss oflungrecoil / decreased Gus

//

VE max

p t(L)

b. X

/ lopes

/fromorigin

/X/< -Gus

pSt (L)

VE MO

C. /

I

-t' P6t (L)

FIGURE 3 Schematic maximum flow-static recoil plots. a. Loss of lung recoil does not affect the maximum flow-static recoil slope. A decrease in the maximum flow-static recoil slope indicates a decrease in upstream conductance. b. Parallel displacement of maximum flow points (heavy continuous line) to higher values of static recoil pressure. In the analysis of

Mead etal. (5) this change is also interpreted as a decrease in upstream conductance. Inter-rupted line indicates a normal maximum flow-static recoil curve. c. Graphical interpretation

ofthemaximum flow-static recoil curve (heavy continuous line) shown in b using the analysis ofPrideetal. (6). Seetext.

consistent differences (12). If specific compliance of the

bronchi were less than that of the alveoli, then the forces distending the bronchi would be systematically greater than transpulmonary pressure (4). In plotting conductance

against P. (L), we are using recoil pressure as an

indi-cator of the forces distending the airways and not

neces-sarily implying that Pa (L) is precisely equivalent to the tissueforcesdistendingtheairways.

The change in conductance with change in static recoil

pressure (AGaw/AP,t(L)) is a function of the radial

dis-tensibility of the bronchial tree and is analogous to the

measure of bronchial distensibility in an isolated bronchus obtained by plotting bronchial diameter versus transbron-chial pressure. AG.aw/APsg (L), however, represents the lumped distensibility of all the bronchial tree and will be affected by changes in any of the bronchial generations. A reduction in AGaw/APst(L) may indicate either stiffness

of individual airways or loss or complete occlusion of

parallel airways (Fig. 2); this is exactly comparable to the

way in which a reduced lung compliance may reflect stiff-ening of individual alveoli or loss of alveoli. With loss of

lung recoil without any intrinsic abnormality of the airway wall or lumen, AGGaW/AP.g (L) will be within the normal

range.

Dynamic performance of the Ilungs: the mnaximitum

flow-static recoil plot. Mead et al. (5) have shown that

VE,MAX at any lung volume where there is a plateau of flow on the isovolume pressure-flow curve can be analysed

in terms of the relationship between Pat(L) and the

con-ductance of the airways upstream to equal pressure points

(conductanceof theupstream segment, G..) VE,MAX=P.(L)-(G.U).

(1)

In normal subjects from about 70% down to about 30% of the vital capacity equal pressure points become fixed on

forced expiration at lobar or segmental bronchi (9), and so in these circumstances the upstream segment corresponds approximately to the intrapulmonary airways. At lower lung volumes in normal subjects and throughout the vital capacity in some patients with chronic airflow obstruction

(13) the equal pressure points are situated in more

periph-eralairways.

Eq. 1 can be expressed graphically by plotting maximum

flow against static recoil pressure (Fig. 3a). With loss of lung recoil pressure AVE,MAX/APat(L) will remain in the

normal range. A reduction in AVE,MAX/AP.t (L) indicates a decrease in upstream conductance. In addition a parallel displacement of maximum flow points tohigher static recoil

pressures without any change in AVE,MAX/AP. (L) will be interpreted in the analysis of Mead et al. as a decrease in

upstream conductance, which is particularly marked at low recoilpressure (Fig. 3b).

Pride, Permutt, Riley, and Bromberger-Barnea (6) de-veloped a slightly different equation to predict VE, MAx at

any lung volume with a plateau of flow on the isovolume

pressure-flowcurve:

(2)

where Ptm' is the critical transmural pressure (difference

between lateral airway and extra-airway pressure) at which the flow-limiting airways narrow sufficiently to restrict flow, and G. is the conductance of the airways in the S segment during forced expiration. In this analysis the S

segment comprises all the airways between the alveoli and those which form the flow-limiting segment. Hence the S

segment will be shorter than the upstream segment of Mead

et al. (5) if Ptm. >0 and longer than the upstream segment

if Pt.'<0. This equation distinguishes two different ab-normalities of the airways, a decrease in conductance of

the smaller airways (G.) and an enhanced collapsibility of

flow-limiting airways (shown by an increase in Ptm'),

which in the analysis of Mead et al. would both be inter-preted as a decrease in upstream conductance. If G. and Ptm' are unaffected by changes in lung volume, their values can be derived from a maximum flow-static recoil plot, G.

being represented by the slope of the maximum flow-static recoil points themselves

_(AVE,

MAX/AP.t(L)) and Ptm' by their intercept on the static recoil axis (Fig. 3c). In this analysis parallel displacement of maximum flow points to

higher recoil pressures would be interpreted as being due

to an increase in Pt.', implying enhanced collapsibility of flow-limiting airways (Fig. 3c).

Experimental procedure. In each subject we measured

total airways conductance, VE,MAx, and P,,(L) over as

wide a range of lung volumes as was possible. Total air-ways conductance (Gaw) was measured in a variable pres-sure, constant volume body plethysmograph by the panting technique (14). As discussed above, the aim was to measure

conductance close to zero flow so that there would be no

dynamic effects on airway dimensions. Patients with severe

Airflow

Obstruction of Chronic Bronchitis and Emphysema

VE,mOx

x

000 -

-o o o- oooo o

o-S I+ +II

en O (10 sC1 tr.in1 t_ - -_fU^ t0_r; -t 1o -l _I'd 10 1.1

14 -tt 1s*f)It *- u: In C4 - esq rs - " 1 - N, - o

,C ' tr,t" _Ce,t'" ,C Co:: - - nc - 'o 't

6~. 6

+,

_ tr, (S 4 M O s C

+++++++++++++++++ +

E4tS X 0 tl. tr, \0 0 X X - f, fl

0, x0 o x0 u, t- _ 4 o t- _ t

-O - - - O 5-- - - O C

0 C5C 6 : C CO

.n U

0~~~~~~~~~0

f,q 0

00-,

--toc~0

00'= c,N N N-.

-11 r- It o

.oc.-')~= N-4- 47 = -~- - =

-: = vS

6 --:= -6= _--__---:_, 1- Z

000 I

tl - -t I, ,l' if; 'o X -, -t -S tr, -n -S t- r- V', "d - =

= 0= 0 00 0 C O O _ O0 0 0 =0

j:j i- j j~j 0 j i C j i i j-Z _ ji

tnCz l, cl,C,N

c 00 lll -1t-- tN

N-C,C't't 00 t- oo 't 00 C~-'-"I

N~~~06 ;

N1-~t-C t0

t--t

.~I"

r- X0 -S

0 -=

U-.R

-S,

el

Ut,11

_- 5

-ZC

=O

Cv t-4

-0

0;

C--.

e-I4 "I)-C 0 m a,0 a) ~

z : 7 n

-1

e

e

0>

Us

04

>U

UCUd

U)

-C)

.-4cd

-Z7

Wo

0 ,0

UCZ>

Cd

CS

U)._

=d00

:>

o

E o > C d

cd 0

"O Y

QC, " - C

CU U'V_

0

>-o 11

airflow obstruction show considerable looping of the ex-piratory pressure-flow curveduring panting, so we measured the slope between zero flow and an inspiratory flow of 0.5 liter/s, during panting at about 2 breaths/s. Dynamic changes on inspiration at these flow rates are small. An average of 15 measurements over a range of lung volumes

was made and a line of best fit drawn by eye through the points. Total lung capacity (TLC) was determined by ob-taining thoracic gas volume by panting against a closed shutter (15) and then adding the volume inspired as the

patient made a full inflation on opening the shutter. The mean of at least four measurements was taken. Functional residual capacity (FRC) and residual volume were derived from separate records of tidal breathing and vital capacity

maneuvers. VE,MAX-volume curves were obtained with the

patient seated within a variable-volume body

plethysmo-graph (16) and breathing out to the room viaa Fleisch No. 3 or 4 pneumotachograph. The box-spirometer system was pressure-compensated and the amplitude and phase of vol-ume signals showed no change with increasing frequency up to 6.5 cycle/s. The pressure drops across the pneumotacho-graph screens were linear up to flows of 400liter/min (No. 3) and 600 liter/min (No. 4). Expiratory flow was plotted

against change in thoracic gas volume on a Tektronix 564

storage oscilloscope (Tektronix, Inc., Beaverton, Ore.).

A series of full vital capacity maneuvers was performed

with efforts varying up to maximum and the largest

expira-tory flows at a given volume were recorded (17). Pa (L)

was measured with an esophageal balloon containing 0.5 ml air (18) at frequent intervals in the vital capacity, volume

being measured with the patients seated within the variable-volume body plethysmograph. A mean pressure-volume

curve was constructed for each patient from at least three closely reproducible curves; occasional curves with more positive esophageal pressures were ignored. Staticexpiratory

compliance was taken as the slope of the expiratory pres-sure-volume curve between FRC and 500 ml above FRC. The forced expiratory volume in 1 s (FEV1), and vital capacity were measured with a timed spirometer.

From these measurements, conductance-static recoil and maximum flow-static recoil plots were constructed as fol-lows: (a) Conductance-static recoil plot, conductance at each lung volume was read off the conductance-volume curve and plotted against static recoil pressure for this

volume. In all subjects an attempt was made to measure both inspiratory and expiratory pressure-volume curves, but in most subjects the expiratory pressure-volume curves were more repeatable. There was relatively little hysteresis between inspiratory and expiratory pressure-volume curves i. the patients and so expiratory pressure-volume curves were used in all except one patient in whom esophageal spasm at full inflation prevented reliable expiratory curves being obtained. (b) Maximum flow-static recoil plot,

P,a(L)

obtained on the expiratory pressure-volume curve was plotted against the value of

V'E,

MAX found at the same volume on the VE, MAx-volume curve. Flows close, to peak

expiratory flow were ignored, since these are

effort-de-pendent. The slope of the maximum flow-static recoil points,

AV19,MAX/AP.t(L), was estimated between 70% and 30% of the vital capacity to obtain G.; the intercept of this slope on the pressure axis was used to estimate Ptm.,

All volumes were expressed at body temperature and pressure.

Suibjects

studied. 10 normal subjects (9 men and 1 woman, average age 34.5 yr) and 17 patients with chronic airflow obstruction (16 men and 1 woman, average age 61.4 yr) were studied. Only two of the normal subjects were

cigarette smokers and nonehad any history of serious

respi-0.24

0

I 0.20

-E

u

X 0.16

NiC)

X 0.12

-.2

ff 0.08 _

T0

0

0.04 I

20 40 60 Ii 100

% Predicted TLC

120 140 160

FIGURE 4 G.w(measured at low flow

rates)

plotted against

lung volume. To correct for differences in size of the

sub-jects lung volume isexpressed as percent of predicted TLC and for conductance flow rate is expressed as predicted

TLC per second. The shaded area indicates the normal

range which extends upwards to higher levels of

con-ductance. The horizontal interrupted line indicates a

nor-mal value of conductance at FRC, corresponding to 0.5 liter/s/cm H20 for a man with a TLC of 6 liter. The open circles indicate the values of conductance when the patients

were asked to pant after a period of quiet breathing (see

text).

ratory disease. The patients all had chronic cough and

expectoration and were present or ex-smokers. They had been under observation for at least 2 yr during which time there had been little variation in airways obstruction, either

spontaneously or after adrenergic bronchodilator drugs or

(in most cases) after controlled trial of prednisolone.

At-tempts were made to select patients who showed the clinical

and physiological features of either the

"emphysematous"

or the "bronchial" types of chronic airways obstruction

(19).

RESULTS

Anthropometric

data and measurements of

static

and

dynamic lung volumes,

static lung compliance, and

air-waysconductancein the normal

subjects

andthe

patients

with

airways

obstruction are summarized in Table I.

The patients were smaller than the normal

subjects

and

the predicted total lung capacity

(TLC)

(20)

of the

largest

normal

subject

was

192%

of the TLC

predicted

for the smallest

patient.

In the

Table,

flow rates have

been

expressed

in liters per

second,

but in

Figs. 4-8,

an

attempthas been made to correct for these great

differ-ences in size by expressing all flow rates as

predicted

TLC per second. In normal children and adolescents maximum flow rates and conductance values have been showntobe

closely

relatedtoTLC

(21

).

FEV,.,

lung volumes, and static lung

compliance.

FEV1 was reduced, and functional residual capacity and

residual volume were increased in all the

patients

with

0.20

N

E

o 0

-)

.-_T0

3

0

0.

0.16

0. 12

0.08

0.04

0

- ,.~~~~~~--or.0

- .-.-:~ -- ---.

~~~~~.0

-0 4 8 12

Pst(L)

cm H20 FIGURE 5 Gas (measured at low flow rates a as predicted TLC per second per centimeter I

against lung recoil pressure. The shaded area

lower part of the normal range. The results

patients are shown. In the three following figur 8) only the patients who had a normal condt

recoil slope (indicated by the thick, continuou those with a very abnormal conductance-static

(indicated bythe interrupted lines) are shown. with intermediate values of conductance-static are indicated by thin, continuous lines.

airflowv obstruction (Table

I).

Values of TL

lung compliance in the patients were more A TLC was often above

130%

of the predicte eight patients hadvalues of static

lung

compl

were greater than those found in any of

subjects.

Relation between total airways conductan

volume. In all patients the conductance-vc vere displaced to higher lung volumes than

mal subjects (Fig. 4). As a result

specific

a

ductance (SGa.w) at FRC (obtained by. c

value of conductance at FRC by the value

liters) was abnormal in all the patients

(1I

addition, in 14 of the17patientsthe value of at FRC was less than 0.4 liter/s/cm H20, xx ally taken as thelower limit of normal. In th three patients the absolute value of conduct

the normal range and the abnormality in specific

con-ductance was entirely due to the increase in FRC. Routine measurements of airways conductance in patients with airflow obstruction are often made at a

volume above FRC measured

_{during quiet breathing,}

since lung volume tends to increase at the onset of the

panting maneuver. When the present patients were asked to pant after breathing quietly in the normal tidal

range, the average lung volume at which conductance

wsas measured was 0.4 liter greater than FRC and

con-ductance averaged 0.08 liter/s/cm H20 greater than the

Value at FRC. In Fig. 4 the open circles indicate the

results obtained when patients were asked to pant after a normal tidal breathing pattern and without any

de-liberate attempt to change lung volume. In the Table,

values of conductance at the actual FRC have been re-corded.

In most

patients

the conductance-volunme slope had a

large intercept on the volume axis. As a result specific

conductanice in the patients will not be independent of

the volume at which it is measured, but will increase ____________ w-ith increase in lulg volume.

16 20 Relationl betzceen. total airways conidutctanice (at loaw

flows)

anid

lung rccoil pressures. There was

consider-able variation in the relation between conductance and ,nd expressed

_P.t(L)

in _the

_patients,

_{with a}

_nearly

_{10-fold difference}

H20)

plotted

indicates the

between

the

hiighest

and lowest

AGaw/.APat(L)

slopes

from all 17 (Table, Fig. 5). Inseven of the patients these slopes fell

.es (6, 7, and w%ithin the range obtained in our normal subjects; in

uctance-static

_{these patients the abnormalities in conductance}

_shown

reol

sl)o

pd

in

Fig.

4 could be attributed to a reduction in

lung

re-The patients coil pressure at agiven lung volume. In contrast, we as-recoil slope sume that the patients with low AGaw/APat (L) slopes

have intrinsic disease of the airway wall or lumen. \NVe were interested in whether there were differences

in the dy-lanaic performance of the lungs of patients C and static with normal and abnormal AGaw/APat(L) slopes. In variable, but subsequelnt figures thereforewe haveconfined our

analy-d value ananaly-d sis to the seven patients wvith normal AGaw/GAP.t(L)

liancewhich slopes and the six patients with the most abnormal the normal slopes (Fig. 5), and have omitted those with intermedi-ate abnormality. The mean FEV1 was 1.27 liter in the

cc and lung patients with normal AGaw,/APut(L) slopes and 0.93 lume points liter in the six patients with markedly abnormal slopes; in the nor- only one of the eight patients studied with an FEV1 of tirways con- less than 1.0 liter had a normal slope. The mean

ex-lividing the piratory static compliance in the patients with a normal of FRC in

-GawGP//\P

(L) slope was 0.56 liter/cm H20, as

com-Pable I). In pared to 0.37 liter/cm H20 in the group with a reduced

conductance slope.

Thich

is usu- Relation between

_D7E,

M4x and

lung

recoil _pressure. In e remaining all patients VE,MAX was reduced at any given value of :ance was in lung recoil pressure. The abnormality of the maximum

0.81

N--J

V --0

a.

-1

x

0

E >s

0.7 I

0.6 1 0.5

_[

0.41

0.3

_[

0.21

0.1

0 2 4 6 8 10 12 14 16

Pst(L) cmH20

FIGURE 6

\TE,

MAX (expressed as predicted TLC per second) plotted against lung recoil pres-sure. Lower part of normal range indicated by shaded area. Continuous lines indicate patients

with normalAG.W/AP,t(L), interruptedlines thosewithamarkedreduction in

AGaw/Pat

(L). flow-static recoil curves was greatest in the patients with

low

AG.w/AP.t(L)

values (Fig. 6).

G. in the normal subjects lay between 0.069 and 0.142 predicted total lungcapacity/s/cmH20;it was below this

normal range in 13 of the 17 patients. Pt.' was above the upper limit of our normal range (+ 1.7 cm

H20)

in 13 patients so thatcommonly the maximum flow-static

recoil curve in the patients showed abnormalities in both

slope (G.) and

intercept

(Ptm').

However the seven

patients with normal

AG8w/AP.t (L)

values had rela-tively little reduction in G.. Three of these patients had

values of G. within the normal range and in three more

G, was between 0.062 and 0.068 predicted

TLC/s/cm

H20. In these seven patients the average value ofG. was

0.072

predictedTLC/s/cm H20 comparedto meanvalues of 0.094 in the control subjectsand 0.047 in the patients with low

AGaw/APat

(L) values. The mean increase in

Ptm' was slightly less in the patients with a normal

AGaw/APat

(L)

slope (+ 2.8cm

H20)

than in thosewith

reduced

AGaw/APat

(L) slopes (+4.0 cm H20). Relationship between total airways conductance at low

flows

and rE,MAX (Fig.

7).

There were considerable

differences

betveen the two groups of patients. In gen-eral those with a low

AGGaw/APat(L)

slope had relatively good

VE,

MAX in relation tothe value oftotal conductance

atthe same lung volume, while the reverse was found in

the patients with a normal AG.W/AP.t (L) slope. DISCUSSION

The striking feature of the results is that in 7 of the 17 patients the observed reduction in conductance (mea-sured at low flows) could be accounted for by the loss of lung recoil pressure. In no patient, however, was the

loss of lung recoil pressure sufficient to account directly for the reduction in VsM.MAx. This difference between static and dynamic measurements is discussed below.

Limitations in the methods.

Previous

workers (3)

who have related airway conductance to lung recoil pressure have obtained lung recoil pressure during

oc-clusion of the shutter at the end of each period of pant-ing. In pilot studies we found that the scatter of such directly obtained conductance-static recoil points was atleast as great as that of conductance-volume points; as our patients tolerated the repeated panting procedure better when they were required to do this without an

0.8

-i_{' 06}

-J

X 0.4

E

.>" 0. 2

0

I II

:12

II,I

;//i@

i

,

rR

-0

0.24

0.08 0.12 0.16

Gow(Predicted TLC/s per cm_H2p

FIGURE 7 Relation between Gaw (measured at low flows) and

\VE,

MAX. For both measurements flow rates are ex-pressed as predicted TLC per second. The shaded area represents the lower part of the normal range. Continuous

lines indicate patients with normal

AG.w/APat

(L), inter-rupted lines those with a marked reduction in

AG.w/

AP. t(L).

esophageal balloon in place, we chose to construct our conductance-static recoil curves by drawing lines of best fit through 12-18 conductance-volume points and through 3-5 expiratory pressure-volume curves in each patient. This difference in technique does not seem to have systematically affected the results, since the

AGaw/

AP.t(L) slopes in our normal subjects are very similar

to those previously reported (3). A possible source of error is that we have compared our normal subjects with patients who were consi(lerably older. W\e know of no evidence as to whether the condtuctanice-static recoil curve changes with age but wve founld no obvious (if-ference in the position or the slope of the curve between the older and younger individuals in ouir nornmal series. Although the maximum flow-static recoil relationship was approximately linear in most of the normal

sub-jects, in about a third of the patients it was curved so that the ARE,MAX/APIt(L) slope declined as static re-coil pressure and lung volume were reduced. In such curves we estimated G. from the lower part of the

AR,B.MAX/AP,t(L)

slope between 50% and 30% of the vital capacity and Ptm. from the intercept of this part of the ARE, MAX/APIt(L) slope, so as to derivethe lowest

possiblevalues ofG. andPtm'.

Significance of the conductance-static recoil plot. In 7 of the 17 patients conductance-static recoil points were within the normal range so that there was no functional

evidence of intrinsic disease of the bronchi. This does not necessarily exclude the presence of anatomical changes in these airways, for the following reasons.

(a)

In diseased

lungs

conductance will tend to rise with increasing frequency of breathing (22) and will

strictly reflect static airway dimensions only if the mea-surement is made at low flow rates and at a very low

frequency of breathing, whereas the present measure-ments were made at a frequency of about 2 breaths/s.

However, values of conductance at 2

cycle/s

in the

patients with normal conductance-static recoil

relation-ships weregreater than 0.2 liter/s/cm H20 at FRC, and in such patients changes in conductance between

fre-quencies of 0.3 and 2 cycle/s are small (see Figs. 6 and 9 in reference 22). Although we cannot exclude

large changes in conductance at frequencies less than

0.3

cycle/s,

it appears unlikelv thatfrequency dependence

of conductance played an important part in explaining

the findings in the patients with normal conductance-static recoil relationships, but it will have led us to

un-derestimate the severity of the airway disease in the pa-tients with more abnormal values of conductance.

(b)

Even at a very low breathing frequency a total air-way conductance within the normal range cannot

ex-clude anlatotmiical changes in the airways, because the

measurement is relatively insensitive to abnormalities

inthe smaller airways (23), and furthermore reflects the

lumped effects of all the airway generations and so might result from the combination of narrowing in some airways and increaseddimensions ofother

airways.

In the patients

wvith

reduced

AG1v/AP1t

(L)

slopes,

the major factor reducing static airway dimensions

was

a reduction in

bronclhial

distensibility, but in addition there was almost always some loss of recoil pressure. We were unable to

distinguish

whether the reduced distensibility

was

due to stiffening of individual

airways

or due to a reduction in the number of

parallel

airways by destruction or occlusion of the

lumilen.

The only

previous

study of the

relationi

between

con-ductance and P,t (i,) in patients

w%-ith

chl-oniic

airflow

obstruction using the present method, appears to be that of Butler, Caro. Alcala, and DuBois (3). In their patients "there was less than the

normiial

change in

air-ways conductance from alterations of

lunig

elastic

pres-sure" but they do not present any further (letails. Jonson (24) has developed a technique of plotting total

lung

resistance (obtained by the esophageal balloon

metlhod)

against lung recoil pressure during the course of an ex-piratory vital capacity maneuver. He found

tlhree

pa-tients.

all with only slight impairment of

FEV71,

in

whlioln

the relation between resistance and lung volune was

abniormal

but the resistance-lung recoil pressure

rela-tion was normal. In this method resistance was mea-sured at an

expiratory

flow of 1

liter/s,

which will lead

to

significant

dynamic

effects on the airways,

especially

in the presence

of

airflow obstruction, so it is probable that

Jonson's technique

will

underestimate the

numnber

of patients

with

normal static

airway

dimensions at a

stani-dard distending pressure. Other authors have

attempted

to distinguish

between

the roles of loss of recoil

pres-sure and of intrinsic

airways

disease on the basis of the

value of

airway

resistance during quiet breathing or

panting at FRC (25. 26). Only three of our seven

pa-tients with a normal conductance-static recoil curve w_{ould have}

_been

picked out by this criterion.

WNlhether

a patient with a normal conductance-static recoil curve

will

have an

abnornmal

conductance at FRC

will

dlepend

on

wk-hether

lung recoil pressure is normalor

low

atFRC.

A better technique

w-ould

be to measure the value of Gas

/P.t(L)

at FRC

(27),

but there are

advantages

in

mlaking

this

nmeasurement

over a

range

of lung

volunmes,

since

Fig. 5

shows

that the distinction

betweeni

a

nior-mal and an

abnormal

conductance-static recoil slope is

least obvious at low lung recoil

pressures.

Significance

of the maximum

floew-static

recoil

plot.

All the patients showed a greater reduction in VE,MAX

than could be accounted for

directly

by loss of

lung

re-coil, so that all had decreased upstream

condutctance

[absolute

value of

Vt:,

MAx

dividedby the value of

P.t(l)

(5)1 during forced expiration. This finding was

0.07

G_{us/Low- U busIG3wwU.7}

N

x _0.06

E

06 _0.05

0.0

v

0.02

0.0

0

0 _{0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0.18 0.20 0.22}

Gaw(Predicted TLC/sper cm H20)

FIGURE 8 Relation between G, (measured at low flows) and GU.. For both measurements flow rates areexpressed as predicted TLC per second. Continuous lines indicate patients with

normal AG.w/AP.t (L), interrupted lines those with a marked reduction in AG."/AP., (L).

Diagonal lines from origin indicate the line of identity between Gaw and Gu, and the line where Gaw is twice G... Normal values of Gus were greater than 0.075 predicted TLC/s/cm

H20at alllung volumes.

but not in those with normal AG../AP5t (L) slopes.

Previously Duffell, Marcus, and Ingram

(28)

have de-scribed normal maximum flow-static recoil relationships in about half of a series of patients with chronic airflow

obstruction, and morerecently

Black,

Hyatt,

and Stubbs

(29) have reported similar findings inpatients in whom

theairflow obstruction was associatedwith al-antitrypsin deficiency. ai-antitrypsin levels were measured and

found to be normal in three of the present seven pa-tients with a normal

AG../AP.t(L)

slope while none of the remaining four patients showed any of the charac-teristic clinical features (earlyonset of disability, strong

family history, or

predominantly

basal

emphysema)

that suggest

al-antitrypsin deficiency. Although

our failure

to find patients with

completely

normal maximum flow-static recoil

relationships

could therefore be

explained,

if ai-antitrypsin

deficiency

was particularly associated

with

uncomplicated

emphysema, webelieve the explana-tion may be that we studied patients with more ad-vanced disease. The group of patients with normal

maximum flow-static recoil curves studied by Duffell

et al.

(28)

had an average forced

expiratory

volume in 0.75 s of 1.44 liter, while two of the four patients found to have normal maximum flow-static recoil re-lationships by Black et al. (29) had a maximum breath-ing capacity within normal limits. Outside the present series we have observed patients with radiological evi-dence ofemphysemaandconsiderable reduction inP,t (L) (butwithout

ai-antitrypsin

deficiency) inwhom

Vu,

MAX-Pat

(L) curves were completely normal. In these

sub-jects, howvever, expiratory flow limitation and the disa-bilitywererelatively slight.

We have considered two

possible explanations

for

our findings that the patients in whom conductance was reduced in proportion to loss of static recoil showed a

disproportionate reduction in

'VE,MAX. First,

it may be

that an abnormality of smaller airways, present in both static and dynamic conditions, is detected by measure-ments of maximum flow but not by measuring G.,. Second, all airway dimensions may truly be normal un-der static conditions but airways contributing to

Gi,

may show enhanced dynamic changes on forced expira-tion. In distinguishing these two possibilities it is use-ful tocompare values of G.- with those for Guson forced

expiration at the same lung volume. In patients with

severe intrinsic airways disease, narrowing of airways of less than 2 mm diameter is responsible for most of the reduction in G., (23). So in these patients,

in-creased frictional losses in small airways will be the

dominant factor in determining the values of both G.

andGu. and these values might be expected to be similar. In fact a close relationship betweenGawandGu.was found in patients with low values of AG.w/AP.t(L), although

Gaw was somewhat higher than

Gu.

(Fig. 8). In part this difference arises because

Gaw

may have been over-estimated by use of the panting maneuver in these

pa-tients. In contrast, the patients with normal values of

AG.w/AP.t

(L), although they had values of upstream conductance similar to those found in the patients with low AG.w/AP.t (L) slopes, had much higher values of

total conductance, which were usually two to three

times the values of Gu. at the same lung volume (Fig. 8). Sinice in the patients with normal AGaw/.APat(L) slopes there wvould be less tendency to overestimate con-ductance by making the measurement during rapid pant-ing, we

postulate

that these large differences arose either because increased dimensions of large airways offset the effects of small-airwav niarrowing on G. or because there were enhanced dynamic changes in airways con-tributing to Gut on forced expiration. Although the ma-jor bronchii Imlav be slightly larger in patients with

em-p)hysema than in normal

subjects (30),

the functional

significaince of this change is doubtful since the con-ductance of central airways (those wvith an internal (liameter greater than 2 mm) was definitely above the normal range in only one of seven emphysematous lungs studied at necropsy (23). We believe it is more likely that the largedifferences between Gaw and Gus were due

to enhanced dynamic changes in the airways. Although such changes are most obvious in the major extrapul-monary airways, lateral pressures in all the

intrapul-monary airways on expiration are less than alveolar

pressure so that even the most

peripheral

airways tend to be narrower than during breath-holding at the same lung volume. If the effective compliance of upstream airways is increased this could lead toenhanced dynamic changes during forced expiration. Further analysis of

maximumii flow-static recoil curves in terms of the

AXM

,MAX/APs,

(L) slope over the range

70%'-30%

of the vital capacity (G.) and of the intercept of this slope

on the static recoil axis (Ptm') supports the presence of

a dynamic effect in these patients. Gs was within or just

below the normal range in six of the seven

patients

with normal conductance-static recoil curves, while Pt.' was

increased to a mean value of + 2.8 cm H20 compared to

the value of - 1.3 cm H120 in our ten normal subjects

(Table I). Hence most of the abnormality in maximum

flow-static recoil curves in these patients wvas due to

parallel

displacemenit

of maximum flow

points

to higher

values of static recoil, a change which is

compatible

with

enhanced

collapsibility

of

flow-limiting airways

(6).

This analysis is open to criticism in that it assumes that

values of

GJ

and Ptm' are

independent

of lung volume so that the relation between maximum flow and static

recoil can be described in terms ofa slopeand

intercept.

Although in some of the present patients this

relation-slhip

was notably curvilinear, this was not the case in those patients who had a normal relation between con-ductanceand Pst

_{(L) (Fig. 7).}

Otherstudies have shown

examples of nearly linear maximum flow-static recoil curves with normal

slopes

but with an

intercept

at

posi-tive values of

Ps,t(L)

in patients with a clinical

diagno-sis of emphysema

(28,

29,

31).

A

positive

Pt.'

_implies

that airways were

limiting

flow when lateral airway

pressure was greater than extra-airway pressure. We

cannot explainthis finding; increases in Pt.' have

previ-ously been described in asthma and have been attributed to increase in the active tension of bronchial smooth

muscle

(6),

but this is unlikely to explain the results

in chronic airflow obstruction. Obviously there is a need

for a more direct assessment of dynamic airway changes thani is provided by analysis of maximum flow-static

recoil curves; nevertheless both the large discrepancies between Gaw and Gu5 and the tendency to an increase in

P,,,' without reduction in G. are most easily explained

by enhanced airway collapsibility of airways at, or on

the alveolar side of, the flow-limiting segment. Several other studies have indicated that dynamic factors are

important in the airflow obstruction of emphvsema. In

themiddle of the vital capacity VE, MAX may be less than a fitth of the value of maximum inspiratory flow at the sanme lung volume (32). Comiipliance of lobarbronchi on

forced

expiration

has been showin to be increased in

emphysematous patients compared to normal subjects (33); this abnormalitity may be explained by atrophic

changes in the

airways,

whlich have been shown to

in-volve lobar and segmental bronchi and several divisions

of the bronchi beyond segmental bronchi (34), implying that alterations in airway compliance in emphysema maybe equally extensive.

Previously the value of Ptm' in normal subjects had been estimated as between -5 and - 10 cm H20 (6). In the

present

normal subjects. the value of Ptmn1' derived

directly from maximum flow-static recoil curves, was

- 0.8 cm H20, wlhich agrees closely with the value of

- 1.3 cm H20 found

by

Permutt and Hyatt ([31] and personal communication). As Pt.' is so close to zero, the two analyses of VE,MAX set out in Eq. 1 and 2 above will not differ significantly in normal subjects.

Role of extrabronchial factors in

c/ironic airflow

ob-strutction.. In 1951 Dayman (2) attempted to define the roles of intrinsic disease of the airway and of loss of

airway-distending forces in patients with severe airflow

obstruction. He suggested that in some forms of emphy-sema, "intrinsic obstruction of the airways may be

slight or even absent." The present results confirm that in some patients with chronic airflow obstruction there

is no evidence of intrinsic obstruction during breathing

at low flow rates. In general these were not the most

severely disabled patients although they often had large increases in static lung compliance. In these patients maximum flow was reduced out of proportion to the

re-duction in P.t(L), implyingtheremusthave been in

ad-dition either fixed intrinsic diseaseof theairways (which for some reason was not detected by measurements of

Gaw) or abnormal dynamic changes in the airways. We

have argued abovethat this reduction in maximum flow

flow-limiting airways or airways on the alveolar side of the flow-limiting segment. Although enhanced collapsibility of extrapulmonary airways presumably indicates a change in the airway wall itself, this is not necessarily the case for intrapulmonary airways where enhanced col-lapsibility might also be due to loss of airway support by lung tissue. Hence in the patients with a normal rela-tion between conductance and P..(L) even the results on forced expiration could be due to loss of extrabron-chial support as originally proposed by Dayman (2). In most of the severest cases of chronic airflow obstruction, however, there must be an abnormality in either the position or the slope of the maximum flow-static recoil relationship, since recoil pressures are rarely reduced below about one-third of the expected values, while maximum flows may be reduced to one-tenth or less of expected values. In advanced disease there is probably

both intrinsic airways disease and loss of airway distend-ing forces. A reduced conductance at a standard P.t(L)

was found inall the lungs studied at necropsy by Hogg, Macklem, and Thurlbeck (23), while all but one of the patients in the present series had some reduction in lung recoil pressure. We suspect that loss ofairway-distending forces commonly contributes to chronic airflow obstruc-tion but is rarely the sole cause of the severest disability.

Note added in proof. Since this paper was submitted, an analysis of the relation between total pulmonary conductance

(obtained by a similar method tothat usedby Jonson [24] ) andstatic lung recoil pressure hasbeenpublished byH. J.H.

Colebatch, K. E. Finucane,and M. M. Smith. (1973. Pulmo-nary conductance and elastic recoil relationships in asthma and emphysema. J. Appl. Physiol., 34: 143). These authors

found that in patients with emphysema but without cough

and sputum the relationship between expiratory conductance

and lung recoil pressure during a single slow expiration

was similar to that in normal subjects, and that in normal

subjects the slope of this relationship did not change with advancing age. These results support our argument that the normal conductance-static recoil relationship found in some of our patients is unlikely to beexplained by the respiratory frequency at which we measured airways conductance.

ACKNOWLEDGMENTS

This work was supported in part by grants from the Na-tional Fund for Research into Crippling Diseases, the

Wates Foundation, and the Tobacco Research Council of the

UnitedKingdom.

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