J Appl Physiol 92: 19431952, 2002.

First published January 11, 2002; 10.1152/japplphysiol.00393.2000.

Determinants of exercise performance in normal men

with externally imposed expiratory flow limitation

IACOPO IANDELLI,1 ANDREA ALIVERTI,2,3 BENGT KAYSER,4 RAFFAELE DELLACA ` ,2,3

5 6 7 1,6
STEPHEN J. CALA, ROBERTO DURANTI, SUSAN KELLY, GIORGIO SCANO,
PAWEL SLIWINSKI,8 SHENG YAN,7 PETER T. MACKLEM,7 AND ANTONIO PEDOTTI2,3
1
Fondazione Don Gnocchi, I-50020 Pozzolatico; 6Clinica Medica III, Universita` di Firenze,
I-50134 Firenze; 2Centro di Bioingegneria, Fondazione Don Gnocchi e Politecnico, I-20148 Milano;
3
Dipartimento di Bioingegneria, Politecnico di Milano, 32 I-20133 Milano, Italy; 4University of
Geneva, CH-1211 Geneva, Switzerland; 5Westmead Hospital, NSW-2145 Sydney, Australia;
7
Meakins-Christie Laboratories, Montreal Chest Institute, McGill University Health Centre,
Montreal, Quebec, Canada H2X 2P4; and 8Department of Respiratory Medicine,
Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland
Received 17 May 2000; accepted in final form 11 December 2001

Iandelli, Iacopo, Andrea Aliverti, Bengt Kayser, Raf-
faele Dellaca`, Stephen J. Cala, Roberto Duranti, Susan
Kelly, Giorgio Scano, Pawel Sliwinski, Sheng Yan, Pe-
ter T. Macklem, and Antonio Pedotti. Determinants of
exercise performance in normal men with externally imposed
expiratory flow limitation. J Appl Physiol 92: 19431952, 2002.
First published January 11, 2002; 10.1152/japplphysiol.00393.
2000.To understand how externally applied expiratory flow
limitation (EFL) leads to impaired exercise performance and
dyspnea, we studied six healthy males during control incremen-
tal exercise to exhaustion (C) and with EFL at 1. We mea-
sured volume at the mouth (Vm), esophageal, gastric and trans-
diaphragmatic (Pdi) pressures, maximal exercise power (W max)
and the difference () in Borg scale ratings of breathlessness
between C and EFL exercise. Optoelectronic plethysmography
measured chest wall and lung volume (VL). From Campbell
diagrams, we measured alveolar (PA) and expiratory muscle
(Pmus) pressures, and from Pdi and abdominal motion, an
index of diaphragmatic power (W di). Four subjects hyperin-
flated and two did not. EFL limited performance equally to 65%
W max with Borg 910 in both. At EFL W max, inspiratory time
(TI) was 0.66s 0.08, expiratory time (TE) 2.12 0.26 s, Pmus
40 cmH2O and VL-Vm 488.7 74.1 ml. From PA and VL,
we calculated compressed gas volume (VC) 163.0 4.6 ml.
The difference, VL-Vm-VC (estimated blood volume shift)
was 326 ml 66 or 7.2 ml/cmH2O PA. The high Pmus and long
TE mimicked a Valsalva maneuver from which the short TI did
not allow recovery. Multiple stepwise linear regression revealed
that the difference between C and EFL Pmus accounted for
70.3% of the variance in Borg. W di added 12.5%. We conclude
that high expiratory pressures cause severe dyspnea and the
possibility of adverse circulatory events, both of which would
impair exercise performance.
dyspnea; respiratory muscles; dynamic hyperinflation; venti-
lation; blood volume shifts
IN HEALTHY HUMANS, EXERCISE PERFORMANCE is not usually
limited by breathlessness. Borg scale rankings of diffi-
culty in breathing do not approach maximal levels (16,
19, 34), although the respiratory muscles may become
fatigued (7, 15, 34). On the other hand, when expira-
tory flow is limited by a Starling resistor during exer-
cise, severe dyspnea develops in normal subjects,
which seriously impairs exercise performance (16). The
purpose of the present study was to find out why and
how externally applied expiratory flow limitation
(EFLe) leads to such difficulty in breathing with result-
ing impairment of exercise performance.
One possibility is dynamic hyperinflation (DH),
which has often been implicated as a cause of dyspnea
and impaired exercise performance in airway obstruc-
tion (4, 6, 9, 25, 26, 28, 38). Another is the pressure
developed by respiratory muscles. This was proposed
in a landmark, but frequently forgotten, paper in 1971
by Potter et al. (30) who discovered a relationship
between expiratory pressures and difficulty in breath-
ing in chronic obstructive pulmonary disease (COPD).
Data supporting the hypothesis that expiratory pres-
sures cause dyspnea during EFLe exercise have been
presented by Kayser et al. (16). However, neither study
measured operating lung volumes (VL) on a breath-by-
breath basis and thus could not assess the role of DH in
producing dyspnea and exercise limitation. Potter et al.
suggested that high expiratory pressures might impair
venous return (30). Thus they implicated circulatory
factors in exercise impairment. Montes de Oca et al.
(23) also suggested a link between breathing mechan-
ics and exercise performance in COPD. They found
that maximal O2 pulse was the best predictor of max-
imal O2 uptake in severe COPD and that inspiratory
pleural pressures (Ppl), in turn, were good predictors of
O2 pulse.
To assess the contributions of DH, respiratory pres-
sure swings, and circulatory factors to breathing sen-

The costs of publication of this article were defrayed in part by the

Address for reprint requests and other correspondence: A. Aliverti, payment of page charges. The article must therefore be hereby
Dipartimento di Bioingegneria, Politecnico di Milano, Piazza L. da marked advertisement in accordance with 18 U.S.C. Section 1734
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http://www.jap.org 8750-7587/02 $5.00 Copyright 2002 the American Physiological Society 1943
1944 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION
Table 1. Subdivisions of lung volume, FEV1, and anthropometric characteristics of the subjects
Subject TLC, liters VC, liters FRC, liters
BK 7.0 5.2 4.3
PS 6.0 4.6 3.2
SY 6.3 4.7 2.9
II 7.7 5.7 3.58
MF 7.5 5.5 3.25
SC 8.2 6.0 4.1
Mean SE 7.1 0.3 5.3 0.2 3.6 0.2
Letters in left column are subjects initials. TLC, total lung capacity; VC, compressed gas volume; FRC, functional residual capacity; RV,
residual volume; FEV1, forced expiratory volume in 1 s; Ht, height; Wt, weight.
sation and exercise performance in normal subjects
with EFLe, we used pressure measurements combined
with optoelectronic plethysmography to measure breath-
by-breath absolute chest wall volume (Vcw) changes
during incremental exercise on a cycle ergometer (1, 8).
We also measured the difference between volume ex-
pired at the mouth and the volume change of the
thorax1 and assumed that this difference was due to
the volume of compressed gas and liquid shifts from
thorax to extremities. Specifically, we tested the hy-
pothesis of Potter et al. (30) that high expiratory pres-
sures caused difficulties in breathing, circulatory ef-
fects, and exercise performance.
METHODS
Subjects. We studied six healthy normal men aged 36.2
3.6 yr with anthropometric characteristics shown in Table 1.
Subjects were all laboratory personnel trained in respiratory
maneuvers. Chest wall kinematics were measured by opto-
electronic plethysmography as previously described (8).
Eighty-nine reflective markers were placed front and back
over the chest wall from clavicles to pubis. Each marker was
tracked in 3D by four video cameras, two in front of the
subject and two behind. A parallel-processing computer inte-
grated the motion of each marker and, by using Gausss
theorem, calculated the Vcw and its compartments. We used
the three-compartment chest wall model of Ward et al. (36) to
measure volumes of the lung-apposed or pulmonary rib cage
(RCp), the diaphragm-apposed or abdominal rib cage (RCa)
and the abdomen. The transverse markers at the level of the
xiphisternum separated RCp from RCa, whereas the mark-
ers along the costal margin separated RCa from abdomen.
The sum of the volume of each compartment equalled Vcw:
Vcw Vrc,p Vrc,a Vab, where Vrc,p, Vrc,a, and Vab are
the volumes of the RCp, RCa, and abdomen, respectively.
Changes in Vcw were assumed to equal changes in lung gas
volume (VL), plus the volume of any blood shifts from thorax
to extremities (VB): Vcw VL VB. Changes in VL were
taken as the sum of the volume of gas expired at the mouth
(Vm) plus the volume of gas compressed (VC): VL Vm
VC. Thus Vcw Vm VC VB Vrc,p Vrc,a Vab.
We were concerned that if EFLe exercise induced sufficient
DH, the area of apposition of diaphragm to rib cage might
disappear, converting a two-compartment rib cage to a single
compartment. Therefore, we monitored the upper border of
the area of apposition (i.e., the border between RCp and RCa)
1
We define thorax as did Roussos (32) as the volume of the chest
wall and thus the sum of rib cage and abdominal volumes. This is in
keeping with the ancient Greek usage of the word thorax.
J Appl Physiol VOL
RV, liters FEV1, liters Ht, m Wt, kg
1.8 4.3 1.74 70
1.4 3.4 1.74 71
1.6 3.5 1.70 60
2.0 4.4 1.84 94
2.0 4.8 1.79 71
2.2 4.1 1.80 80
1.8 0.1 4.1 0.2 1.77 0.02 74.3 4.7
continuously during exercise by ultrasound and found that
the area was well maintained even in the presence of DH.
Gastric (Pga) and esophageal pressures (Pes) were mea-
sured by standard balloon-tipped catheters connected to
pressure transducers and used as indexes of abdominal (Pab)
and pleural pressures (Ppl). Mouth pressure (Pm) was mea-
sured by a tube connecting the mouthpiece to a pressure
transducer. Transpulmonary pressure was taken as the dif-
ference of Pm and Pes (Pm Pes), transdiaphragmatic
pressure (Pdi) as the difference of Pga and Pes (Pga Pes),
and chest wall elastic recoil pressure (Pcw) as the difference
of Ppl and atmospheric pressure (Pb) during relaxation. For
the three chest wall compartments, Ppl Pb was taken as
the pressure difference across RCp and Pab Pb for RCa and
abdomen (1, 36). Flow was measured by a pneumotachy-
graph attached to the mouthpiece, and its integral was used
to measure tidal volume (VT), respiratory frequency (f),
minute ventilation (V E), inspiratory time (TI), expiratory
time (TE), duty cycle (TI/Ttot) and mean inspiratory flow
(VT/TI). Mean flows of the chest wall compartments between
zero flow points were calculated as their volume changes
divided by TI or TE. Vab/TI was used as an index of dia-
phragmatic shortening velocity and Pdi (Vab/TI) as an in-
dex of diaphragmatic power (W di) (1).
Protocol. Each subject was studied on two occasions. On
both, lung and chest wall relaxation pressure-volume curves
were measured by having the subjects breathe into total lung
capacity and then relax and breathe out passively through a
high resistance to functional residual capacity (FRC). These
maneuvers were repeated until the relaxation curves were
reproducible, Pm finished at zero, and Pdi was zero through-
out. From these data, we obtained the elastic recoil pressure
of the lung as transpulmonary pressure, of the chest wall as
chest wall elastic recoil pressure, of RCp (Prc,p Ppl Pb),
of RCa (Prc,a Pab Pb), and of abdomen (Pab Pb) as
functions of VL, Vcw, Vrc,p, Vrc,a, and Vab, respectively.
After obtaining these data, we stimulated the phrenic nerves
with single shocks, bilaterally, transcutaneously with the
airway closed at relaxed FRC both sub- and supramaximally
and measured the resulting rib cage distortions as a function
of Pdi (1). This was done to measure the restoring forces
resulting from rib cage distortion, if any existed, during
EFLe exercise (1). The subjects then performed an incremen-
tal exercise test either to determine maximum power output
max) under control conditions or to measure exercise per-
(W
formance when exhaling through a Starling resistor that
limited expiratory flow to 1 l/s, thereby simulating COPD.
During exercise, subjects breathed through a mouthpiece and
pneumotachygraph, which was attached to a Hans Rudolph
valve, which separated inspiratory and expiratory flow. Flow
limitation was achieved by putting the Starling resistor on
the expiratory port of the valve. A 2-l jar was placed parallel
92 MAY 2002 www.jap.org
 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION
with the Starling resistor, which acted as a capacitance so
that, at the beginning of expiration, flow was somewhat
greater than 1 l/s, whereas at the end it was somewhat less
(34a). Flow-volume loops during maximal EFLe exercise and
during control exercise at the same workload are shown in
Fig. 1.
After 3 min of spontaneous breathing, subjects began
pedalling on a cycle ergometer. After starting at zero load,
workload was increased in 25-W steps every 4 min until
exhaustion. Data were gathered during the last 40 s of each
workload, including the subjects subjective assessment
of breathing difficulty using a 10-point Borg scale. We ran-
domized the order in which these two exercise tests were
performed. W max for both control and EFLe exercise was
defined as the highest level of exercise that could be sus-
tained for 4 min.
Data analysis. During quiet breathing and control and
flow-limited exercise, we measured end-expiratory and end-
inspiratory Vrc,p, Vrc,a, Vab, and Vcw at each workload. All
volumes reported, except when otherwise specified, are the
ensemble averages over the last 40 s of each run.
Campbell diagrams containing the static deflation pres-
sure-volume curve of the lung, the relaxation pressure-vol-
ume curve of the chest wall, and dynamic pressure-volume
loops during exercise were used to calculate alveolar pres-
sure (PA) and the pressures developed by the expiratory
muscles (Pmus). Pressures developed by rib cage and abdom-
inal muscles were calculated as the distance between dy-
namic and static relaxation pressure-volume loops for RCp
and abdomen, respectively, as previously reported (1, 36). We
estimated velocity of shortening of rib cage muscles and
abdominal muscles as Vrc,p/TI and Vab/TE, respectively,
and calculated power as the product of pressure and flow, as
we had done previously and reported in detail in the com-
panion paper (1, 2).
To measure rib cage distortion, we first plotted Vrc,p vs.
Vrc,a during relaxation at different VL to obtain the undis-
torted configuration of the rib cage. Distortion was then
measured as the perpendicular distance between a given
configuration after phrenic stimulation and the relaxation
line and expressed as a percent of Vrc,p (10, 18).
J Appl Physiol VOL
1945
Fig. 1. Example of flow volume loops
during maximal expiratory flow limita-
tion (EFL) exercise (B) and at the same
workload during control exercise (A) in
a hyperinflator. Also shown are loops
during quiet breathing at rest. Vol-
umes were measured by optoelectronic
plethysmography so that the decrease
in volume before end inspiration (insp)
and the increase in volume before end
expiration (exp) are due to gas com-
pressibility and liquid shifts. FRC,
functional residual capacity.
Differences between volume expired at the mouth and
optoelectronic plethysmographic volumes were evaluated by
plotting the integral of flow at the mouth against the Vcw
measured optoelectronically. From measured values of PA,
the operating VL measured plethysmographically, and sepa-
rately measured subdivisions of VL, we calculated VC from
Boyles law. We subtracted this volume from the difference
between plethysmographic and integrated flow volumes to
obtain the VB during exercise: VB Vcw Vm VC.
Statistical analysis. To obtain determinants of EFLe exer-
cise performance compared with normal exercise, we used
the difference between Borg scale ratings of breathing effort
at the same exercise workload with and without EFLe
(Borg) as the dependent variable. We tested a wide variety
of tentative, predictive, independent variables comprising
various inspiratory and expiratory pressures, breathing pat-
tern indexes, the chest wall and its compartmental volumes,
and power output of the diaphragm. Pressures and powers
developed by muscles were obtained from the companion
paper (2). Linear correlation coefficients were obtained for all
of the tentative independent variables. Those with P
0.0002 (r2 42.0) were retained for further analysis. We then
developed a model and performed a multiple stepwise linear
regression analysis to obtain the parameters that best pre-
dicted flow-limited exercise performance.
Significance of differences between control and Starl-
ing runs was performed by the nonparametric Wilcoxon
matched-pairs test.
RESULTS
Volume displacements and exercise workload. Dur-
ing the flow-limited run, four subjects hyperinflated
dynamically at the highest EFLe workload, whereas
the remaining two subjects did not. We have analyzed
these two subjects, called euvolumics, separately from
the other four. Exercise workload appeared to be
equally impaired in both groups, as shown in Table 2.
Mean volume displacements SE, as a function of
exercise workload in these two groups, are shown in
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1946 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION

max during control and flow-limited run

Table 2. W not abdominal displacement. The contribution of RCp
to this increase was greater than that of RCa. Flow
W max,S/
Subject max,C, W
W max,S, W
W max,C, %
W
limitation in the euvolumics produced very little
change in exercise volume displacements. Euvolumics
BK, h 275 175 63.6 end-expiratory Vcw were, if anything, surprisingly less
PS, e 200 125 62.5
SY, e 150 100 66.7 during flow-limited exercise. In contrast, the hyperin-
II, h 175 100 57.1 flators had a normal decrease in end-expiratory Vcw
MF, h 150 125 83.3 until they reached an exercise workload of 37.5% W max.
SC, h 200 125 62.5
Then at 50% Wmax, end-expiratory Vcw increased, but
Mean SE 191.7 19.0 125.0 11.2 66.0 3.7
not above FRC (0.0 on the ordinate). Finally at the
max, exercise maxi-
Letters in left column are subjects initials. W maximal EFLe workload (65% W max), hyperinflators
mal workload; C, control run; S, flow-limited run; h, hyperinflator; e, were able to achieve an end-expiratory volume that
euvolumic.
exceeded FRC by 850 ml. All chest wall compart-
ments contributed to this increase, but only end-expi-
Fig. 2. Figure 2A is the results in the hyperinflators, ratory Vrc,p and Vrc,a were greater than their volumes
and Fig. 2B is the euvolumics. In both exercise runs at FRC. It is notable that, despite the lack of an effect
and in both groups, the progressive increase in end- of severe flow limitation on volume displacements in
inspiratory volume with exercise workload was due the euvolumics, maximal exercise performance was
almost entirely to an increase in Vrc,p and Vrc,a. There impaired to the same extent as the hyperinflators at
was little or no increase in end-inspiratory Vab. The 65% W max. In all subjects, exercise was terminated by
hyperinflators (but not the euvolumics) increased end- intense difficulty in breathing when Borg scale ratings
inspiratory volume and approached total lung capacity reached 9 or 10.
at the highest EFLe workload compared with control. Breathing pattern. In Fig. 3, the breathing pattern is
Again, this was due to an increase in rib cage volume, shown as measured by integration of flow at the mouth.

Fig. 2. Mean SE volumes of the chest wall and its compartments during control (circles) and flow-limited
(triangles) exercise. Closed symbols are end expiration, and open symbols are end inspiration. A: hyperinflators. B:
euvolumics. CW, chest wall; RCp, lung-apposed rib cage; RCa, diaphragm-apposed rib cage; AB, abdominal volume;
QB, quiet breathing. Abscissa is exercise workload as a percentage of maximum control. Far right triangles in each
diagram represent maximal EFL exercise.

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 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION
The four plots are of V E, VT, f, and TI/Ttot. During
control exercise, the data for all six subjects were
averaged. During EFLe exercise, the data for the eu-
volumics were analyzed separately from those for the
hyperinflators. V E tended to be less during flow-limited
exercise, and this difference became greater as exercise
workload increased. At zero workload, EFLe V E was
97% of control zero workload VE but was only 88% at
the maximal EFLe workload. VT was increased during
flow-limited exercise until the last exercise workload,
when it became equal to the control VT in the euvolu-
mics and less than control in the hyperinflators. The f
was less than control during all flow-limited exercise
workloads in the euvolumics. This was also true for the
hyperinflators at the workloads less than the maxi-
mum achieved with flow limitation, but during the last
workload there was a brisk increase in f in this group.
Because VT was higher and f less during EFLe exer-
cise, alveolar ventilation might have been preserved
despite the reduced V E. Therefore, we calculated alve-
olar ventilation on the basis of an assumed anatomical
dead space equal in milliliters to body weight in
pounds. At workloads higher than 0 W, alveolar venti-
lation was decreased on average by 9%. For a given
CO2 production, this would result in an 11% increase
in arterial PCO2 over that during control exercise (4.5
Torr).
During control exercise, TI/Ttot increased gradually
with exercise workload from 40 to 48%. In contrast,
J Appl Physiol VOL
1947
Fig. 3. Mean SE values of ventilatory parameters
during control (F) exercise (6 subjects) and during flow-
limited exercise. E, Hyperinflators; , euvolumics. Or-
dinates are as in Fig. 1.
flow limitation resulted in a progressive drop in TI/Ttot
to a value of 23%, which was similar for both groups.
Table 3 gives the values for VT/TI, TI, TE, and f at the
maximal workload achievable during the flow-limited
run and at the same workload during control exercise.
Although the effects of flow limitation on f were vari-
able and the mean values not significantly different,
the effects on mean inspiratory flow and TI were sys-
tematic. Mean inspiratory flow increased by an aver-
age of 65%, TI was reduced by nearly 50%, and TE
increased by 30%.
Pressure-volume relationships. Figure 4 shows
Campbell diagrams with examples of dynamic pres-
sure-volume curves at the maximal levels of EFLe
exercise in a euvolumic (Fig. 4A) and a hyperinflator
(Fig. 4B). The left heavy line in Fig. 4, A and B, is the
static pressure-volume curve of the lung, and the right
heavy line is the relaxation curve of the chest wall. A
loop during quiet breathing is also shown encircling
the static pressure-volume curve of the lung with end-
expiration at FRC. Note the large transpulmonary
pressure swings during exercise, amounting to 7080
cmH2O. As pointed out above, the euvolumic was able
to decrease VL normally well below FRC during EFLe
exercise, while end-expiratory volume remained sta-
ble. The hyperinflators end-expiratory VL was above
FRC and showed a progressive increase over the four
breaths illustrated.
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1948 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION

Table 3. Ventilatory parameters

VT/TI, l/s TI, s TE, s f, min1

Subject C S C S C S C S

BK 2.00 4.20 1.30 0.42 1.80 1.60 19.30 29.90

PS 1.60 2.70 1.20 0.87 1.50 2.30 22.20 18.70
SY 2.00 3.40 1.20 0.68 1.50 3.10 22.10 15.80
II 1.70 2.80 1.20 0.87 1.70 2.50 21.10 18.00
MF 1.80 2.50 1.10 0.48 1.50 1.50 22.70 30.90
SC 2.00 2.70 1.50 0.64 1.80 1.70 18.60 26.10
Mean SE 1.85 0.07 3.05 0.26 1.25 0.06 0.66 0.08 1.63 0.06 2.12 0.26 21.00 0.69 23.23 2.67
P 0.0033 0.002 NS NS
Letters in left column are subjects initials. VT/TI, mean inspiratory flow; TI and TE, inspiratory and expiratory time, respectively; f,
breathing frequency; NS, not significant.

A prominent feature of both traces is the markedly
increased expiratory PA. Although inspiratory PA was
remarkably low between 20 and 30 cmH2O, expira-
tory PA exceeded 50 cmH2O in both individuals. Evi-
dently, when expiratory flow is markedly limited, normal
subjects develop greater pressures in a futile attempt to
increase flow. This is demonstrated by the values of
Pmus given by the horizontal distance between the chest
wall relaxation curve and the dynamic expiratory loops
that reached 50 cmH2O in both subjects. The small
increase in volume toward the end of expiration accom-
panying the sudden decrease in PA is largely due to gas
decompression. These two examples are the highest val-
ues of expiratory pressure that we measured. There was
considerable between-individual variation with maxi-
mum values of PA ranging from 27 to 59 cmH2O.
Gas compression and blood volume shifts. The differ-
ences between volumes measured by optoelectronic
plethysmography and those measured by integration of
flow at the mouth during maximal EFLe exercise are
shown in Fig. 5. Each panel is the ensemble average of
the last few breaths during the run in a given subject.
During the control run at the same level of exercise, the
two volume traces moved along the line of identity and
no differences were detectable. By contrast, in EFLe
exercise, expiratory plethysmographic volumes led the
volume of gas expired at the mouth systematically,
producing a clockwise loop so that the volume change
of the chest wall was greater than the volume expired
at the mouth in all subjects. During inspiration, the
differences were small. From the operating VL mea-
sured optoelectronically and from PA, we estimated VC
and subtracted this from the total volume difference to
obtain VB. By dividing VB by PA, we estimated the
amount of blood shifted per unit change in PA. These
data are shown in Table 4.
Rib cage distortion. During both control and EFLe
exercise, rib cage distortions were small and generally
within 1%. Because the pressure cost of such distor-
tions is small (10, 18), we ignored them.
Determinants of breathing sensation. Figure 6 shows
the Borg scale rankings of breathing effort. The closed
circles are the means SE for all six subjects as a
function of workload during the control runs. The open
squares give the results for EFLe exercise in the hy-
perinflators and the closed triangles the results in the
euvolumics. Breathing sensation did not limit control
exercise; the Borg scale rating reached a value of only
4 (range: 26) at W max. In contrast, as we previously
observed (16) during flow-limited exercise, performance
was impaired because of intense difficulty in breathing;
the mean Borg scale ranking at the end of exercise was
9.3 (range: 910), and the subjects on average were only
able to exercise to 65% of control W max.

Fig. 4. Campbell diagrams at the high-

est EFL exercise workload in a euvolu-
mic (A) and a hyperinflator (B). Vcw,
absolute chest wall volume; Pes, esoph-
ageal pressure. The heavy line with a
negative slope is the quasi-static defla-
tion pressure-volume curve of the lung
from total lung capacity to FRC. The
heavy line with the positive slope is the
quasi-static relaxation pressure-volume
curve of the chest wall. The large loops
are the pressure-volume relationships
during exercise. The narrow ellipse is
the loop during QB. The minimum vol-
ume on this loop is at FRC. Alveolar
pressure at any point in time is the hor-
izontal distance from a dynamic loop to
the static pressure-volume curve of the
lung. Pressure developed by the respira-
tory muscles at any point in time is the
horizontal distance from a dynamic loop
to the chest wall relaxation curve.

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 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION 1949

Fig. 5. Instantaneous changes in volume of gas measured at the mouth (Vm) and that measured plethysmo-
graphically (Vcw) during control and flow-limited exercise in each subject. The data are ensemble averages of
several breaths during the last 20 s of the highest level of exercise achieved with EFL. Control breaths follow the
line of identity; loops during flow-limited exercise are clockwise; Vcw leads Vm, and expiratory Vcw are
systematically greater than expiratory Vm. Letters in top left of each panel are subjects initials.

There was no difference in breathing sensation be-
tween the euvolumics and the hyperinflators at higher
workloads, although the hyperinflators tended to have
higher rankings at lower exercise levels before they
hyperinflated. The degree of exercise limitation in both
averaged 65% of control W max (range: 5783). Thus
both groups had the same degree of exercise impair-
ment. Hyperinflation did not impair exercise perfor-
mance in the euvolumics.
abdominal muscles (2) and the global differences in Pmus
(Pmus) measured from Campbell diagrams (P
0.00001, r2 0.703). Next were ventilatory parameters
reflecting the prolonged TE and shortened TI (TI/Ttot:
P 0.00001, r2 0.519; VT/TI: P 0.00001, r2 0.513).
Finally, parameters reflecting central inspiratory drive
were important. These were the change in Pdi (Pdi; P
0.00001, r2 0.503) and fold changes in W di (W
di; P
0.0002, r 0.420). Indexes of hyperinflation, such as
2

The parameters that correlated best with Borg were changes in end-expiratory and end-inspiratory Vcw, were
the changes in Pmus developed by the rib cage and either nonsignificant or had r2 values of 0.370.
From these preliminary linear regressions, we con-
structed a model using Pmus, VT/TI, and W di as
Table 4. Gas compression and blood volume shifts
independent variables. Multiple stepwise linear regres-
VL (pl-sp), Vblood/PA, sion analysis revealed that this model accounted for
Subject ml Vcomp, ml Vblood, ml ml/cmH2O 82.8% of the variance in Borg. Of that value, 70.3% was
accounted for by Pmus, and W di added an additional
BK 499 197 302 7
PS 520 132 388 8 12.5%. VT/TI was rejected. No other model tested ac-
SY 410 87 323 8.2 counted for as much of the variance in Borg as these two
II 792 195 597 11.9 variables. W di turned out to be more important than
MF 233 119 114 4.2
SC 478 248 230 3.9
other variables that were better correlated with Borg
Mean SE 488.7 74.1 163.0 24.6 325.7 66.3 7.2 1.2 because it was the least well correlated with Pmus.
Letters in left column are subjects initials. VL (pl-sp), difference
DISCUSSION
between volume of gas measured at the mouth (sp) and volume
change of the chest wall (pl); Vcomp, volume change due to gas
compression; Vblood, volume of blood shifts from trunk to extremi-
Critique of methods. The introduction of optoelec-
ties [VL (pl-sp) Vcomp]; Vblood/PA, amount of blood shifted for tronic plethysmography solves the difficult problem of
unit increase in alveolar pressure (PA). tracking absolute VL changes on a breath-by-breath
J Appl Physiol VOL 92 MAY 2002 www.jap.org
1950 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION
Fig. 6. Mean SE Borg scale ratings as a function of exercise
workload (abscissa) expressed as percent control of maximal work
rate. F, Control exercise; E, flow-limited exercise, hyperinflators; ,
flow-limited exercise, euvolumics. The difference between the two
curves (control and flow-limited exercise) was taken as the depen-
dent variable for regression analysis of determinants of exercise
performance.
basis. In addition, we used the difference between this
volume measurement and the volume expired at the
mouth during a single breath to calculate VC and the
volume of liquid shifted from the thorax to the extrem-
ities. This assumes that this volume difference can
only be due to gas compression and/or liquid shifts to
the extremities. That the liquid displaced is blood
seems reasonable as shifts of extravascular fluid of the
magnitude we measured are unlikely. The blood could
come from the lung, rib cage, or abdomen, and the
shifts must be to the extremities because liquid dis-
placements from one thoracic compartment to an-
other (e.g., from lung to rib cage or abdomen) would
not be detected by measurement of Vcw. Shifts from
rib cage to abdomen could not be distinguished from
isovolume maneuvers produced by respiratory mus-
cle contraction.
EFLe mimics EFL due to dynamic compression of
intrathoracic airways in that flow becomes indepen-
dent of driving pressure. There was significant volume
dependence of expiratory flow during each expiration
because the jar in parallel with the resistor acted as a
capacitance. Nevertheless, EFLe produced by the Star-
ling resistor does not lead to dynamic compression of
intrathoracic airways as occurs in physiological EFL.
Presumably, if VL had decreased to the point where the
maximal expiratory flow was 1 l/s, dynamic compres-
sion of intrathoracic airways would have occurred and
Pm would have fallen to zero. This was not observed.
Thus any feedback evoked by dynamic compression
was absent in our subjects. However, our data show
J Appl Physiol VOL
that tracheobronchial compression is not required to
impair exercise performance, limitation of exercise by
breathlessness, and CO2 retention (2, 16). Similar re-
sults have been reported by Wood and Bryan (37) in
normal subjects exercising at depth and by others in
the absence of any flow limitation at all; adding high
external inspiratory and expiratory resistances is suf-
ficient (11, 29).
In our experiments, in contrast to pathophysiological
flow limitation, no benefit in terms of increased flow
was obtained by DH. This may be a reason why two
subjects remained euvolumic and the other four sub-
jects only hyperinflated toward the end of flow-limited
exercise.
Factors limiting exercise performance. In our exper-
iments, exercise performance was limited by severe
dyspnea. In every case, Borg scale ratings reached
910, confirming our earlier report (16). In the pres-
ence of EFL, DH has been strongly implicated as a
cause of breathlessness and impairment of exercise
performance (4, 9, 25, 26, 28, 38). A number of factors
may be involved, including shortening of diaphrag-
matic fiber length, threshold load (9, 21, 22), progres-
sive decrease of inspiratory capacity to a value lower
than the desired VT (4, 5, 6, 10, 26, 28, 38), a decrease
in V E (4, 5), and a decrease in lung compliance, which
increases the elastic work of breathing.
There is not uniform agreement that DH is the
principle factor causing exercise limitation. Noseda et
al. (24) found that an index of central inspiratory drive,
peak inspiratory flow, was the best predictor of dys-
pnea during exercise in COPD. Because we only stud-
ied two euvolumics and four hyperinflators, generali-
zations and statistical comparisons between these two
groups are not meaningful. However, our data in eu-
volumics show that EFLe does not necessarily lead to
DH, although exercise was terminated by breathless-
ness equal in degree to that experienced by hyperinfla-
tors with the same impairment of performance. In the
other four subjects, DH reduced inspiratory reserve
volume almost to zero, but it was a relatively late
occurrence, developing only near the end of EFLe ex-
ercise (Fig. 2) after Borg scale ratings had significantly
increased (Fig. 5). Thus, in our experiments, DH did
not lead to impaired exercise performance in two sub-
jects and did not contribute to the dyspnea experienced
by the other four until they reached the highest EFLe
exercise level. This makes us suspect that its role may
be overemphasized.
Montes de Oca et al. (23) and Potter et al. (30)
specifically linked the mechanics of breathing to circu-
latory factors during exercise in COPD with the impli-
cation that the link between abnormal mechanics of
breathing and impaired exercise performance may be
via the circulation rather than a malfunctioning ven-
tilatory pump per se.
There is considerable evidence that energy supplies
to locomotor muscles are inadequate at maximal exer-
cise workloads in both healthy subjects and patients
with COPD (3, 31, 33) when there is competition be-
tween respiratory and locomotor muscles for the avail-
92 MAY 2002 www.jap.org
 EXERCISE PERFORMANCE WITH EXPIRATORY FLOW LIMITATION
able energy supplies. At maximal exercise in trained
normal subjects, respiratory muscles consume about
15% of total body O2 consumption and take a similar
percentage of the cardiac output (13, 14). If one applies
this concept to COPD where the oxygen cost of breath-
ing is about an order of magnitude greater than normal
(20), the competition becomes much more severe so
that as much as 50% of the O2 consumption and cardiac
output may go to the respiratory muscles (3). Richard-
son et al. (31) reported that the mass specific O2 con-
sumption of the quadriceps muscle in COPD was much
greater when it was the only muscle exercising than it
was at maximal whole body exercise. Thus, if energy
supplies are adequate, locomotor muscles can perform
more work. It appears that there are some patients
with COPD in whom exercise may be limited by energy
supplies that are insufficient to meet demands.
Blood volume shifts and respiratory pressure swings.
The high expiratory pressures we measured during
EFLe exercise caused gas compression and what we
assume to be VB averaging 325.7 ml from the thorax to
the extremities (Table 4). Although we are unable to
determine how much was displaced from the abdomen
and how much from the lung, only a small fraction
displaced from the pulmonary capillaries could effect
distribution of ventilation-to-perfusion ratios because
pulmonary capillary VB is only 220 ml during exer-
cise (35). This might increase alveolar dead space and
could be a factor in the CO2 retention that occurs (34a).
These blood shifts show that expiratory pressure
swings have circulatory effects in addition to their
effects on respiratory sensation (16). They did not occur
during normal exercise (Fig. 5) and are therefore a
specific and significant effect of high expiratory pres-
sure.The reasons for the increased pressures are two-
fold (2). The enforced slowing of expiratory flow de-
creased expiratory muscle velocity of shortening that,
for a given degree of activation, increases force devel-
opment according to the muscles force-velocity rela-
tionship (30). In addition, we found that both inspira-
tory and expiratory muscle power were increased
during EFL exercise compared with control (2), sug-
gesting that there was an increase in central drive
probably secondary to CO2 retention (2, 16).
Potter et al. (30) thought that the high PA during
exhaustive exercise in COPD might impede venous
return and could impose a limitation on the cardiovas-
cular response to exercise in patients producing a sit-
uation similar to a Valsalva maneuver. Our data show
that, during EFL exercise, TE averaged 2 s whereas
TI was only 0.7 s. (Table 3). These data combined
with the pressures confirm the presence of a Valsalva-
like maneuver. However, the effects of Valsalvas ma-
neuver during exercise are unknown.
Determinants of EFLe exercise performance. Because
linear regression analysis was performed on the differ-
ence in Borg scale rankings as the dependent variable
and the differences in a variety of physiological param-
eters as independent variables, between control and
EFLe exercise, our analysis is different from previous
studies attempting to define determinants of exercise
J Appl Physiol VOL
1951
performance in COPD where control experiments can-
not be performed in the same subject. In developing a
model for the multiple stepwise linear regression, we
chose an index of expiratory muscle recruitment,
Pmus (e.g., Fig. 4), VT/TI as a reflection of increased
shortening velocity of of inspiratory muscles (2) and
thus their loss of force-generating ability and the in-
crease in W di as an index of central drive (2). Analysis
showed that Pmus accounted for 70.3% of the vari-
ability in Borg and W di for an additional 12.5%.
VT/TI was rejected. We conclude that Pmus was an
important contributor to dyspnea during EFLe exer-
cise. The contribution of central inspiratory drive is in
agreement with the importance of peak inspiratory
flow found by Noseda et al. in COPD (24).
Relevance to COPD. It is uncertain how relevant our
studies are to COPD. Although we have produced three
major pathophysiological features of COPD in normal
subjects, namely dyspnea, exercise limitation, and CO2
retention, the fact that the sensation induced by dy-
namic compression of intrathoracic airways (38), which
may inhibit expiratory muscle recruitment (27), does
not occur with the Starling resistor may have contrib-
uted to the high expiratory pressures we measured.
Such pressures have rarely been reported in COPD, yet
both Potter et al. (30) and Dodd et al. (12) reported a
mean peak expiratory pressure at maximal exercise in
COPD of 22 cmH2O with large between-individual
variations. In 6 of 12 patients studied by Potter et al.
(30), EEVL increased by 50% of resting VT, and there
was no decrease in inspiratory capacity. Similarly,
Calverley (personal communication) found no DH dur-
ing incremental exercise in 8 of 20 COPD patients.
These findings suggest that the individual response to
EFL exercise in COPD is heterogenous but similar to
what we found in normal subjects. Some patients hy-
perinflate whereas others do not. There is a large
between-individual difference in the degree of expira-
tory pressure produced, which in some patients is ex-
cessive. Perhaps the relevance of our model to COPD
may be to generate testable hypotheses. Our laborato-
rys studies (16) suggest that high expiratory presures
might be a factor limiting exercise in COPD. If so, it
might be possible by appropriate physiotherapy to
train patients to derecruit expiratory muscles during
exercise and improve performance.
Supported by the Breath Project (Biomed 2 Programme) and The
Respiratory Health Network Centres of Excellence, funded by The
Medical Research Council of Canada.
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