Most investigators have measured changes in
air-way obstruction in the post-exercise period by only
one parameter, peak expiratory flow rate (PEFR).12
SUPPLEMENT
883
A Comparison
of Pulmonary
Function
Tests
in Detecting
Exercise-Induced
Bronchoconstriction
Jerome M. Buckley, M.D., and Joseph F. Souhrada, M.D., Ph.D.
From the National Jewish Hospital and Medical Center. and the Departments of Pediatrics
and Medicine, University of Colorado Medical Center, Denver.
ABSTRACT. In an attempt to compare most of the
avail-able pulmonary function tests in detecting airway
obstruc-tion after exercise, two studies were conducted. In the
first study 24 bronchodilator-dependent asthmatic boys
were evaluated before treadmill exercise (baseline) and
at 7 and 30 minutes afterwards. The following
pulmon-ary function parameters were measured: forced vital
ca-pacity (FVC), forced expiratory volume in one second
(FEV1), maximum mid-expiratory flow (MMEF), peak
ex-piratory flow rate, thoracic gas volume, airway resistance,
specific airway conductance (SGaw), and closing
vol-ume (CV). Results showed that SGaw, MMEF, and CV
were the most sensitive parameters reflecting changes in
airway caliber. Less significant changes also appeared in
FEVI and in FVC. The significance of these changes and
their relationships to other parameters are discussed.
In an attempt to better understand the effects of
air-way obstruction on the maximum-expiratory flow-volume
curve (MEFV curve) after exercise, a second sludy was
conducted. Comparisons were made between “classical”
parameters such as MMEF (measured by spirometry),
SGaw (measured by body plethysmography), and
flow-volume parameters (measured by wedge spirometer).
Six-teen asthmatic subjects (9 to 12 years of age) whose
airway obstruction was further exacerbated by exercise of
a moderate work load on the treadmill (2 w/kg of body
weight) were studied. The asthmatic subjects were tested
prior to exercise and at 7 and 30 minutes after exercise.
All the measurements mentioned above were done in a
randomized manner. When both MMEF and SGaw were
decreased in the post-exercise period, significant correla-tions were obtained between these “classical” parameters
and all of the flow-volume parameters. However, when
only one of the two was decreased, no correlation could
be obtained with any of the flow-volume parameters. It
was concluded that under certain conditions flow-volume
curves reflect airway obstruction satisfactorily, but under other conditions they appear to be less sensitive than the “classic” parameters. These results are also discussed. Pediatrics, 58 (suppl): 883-889, 1975.
The obvious question which arises is how exercise
in the asthmatic patient affects the other available
pulmonary tests which reflect airway obstruction.
It has been suggested that different pulmonary
func-tion tests may reflect obstruction of different parts
of the tracheobronchial tree.’ The purpose of this
discussion is to consider the value of selecting
dif-ferent parameters for detection of airway
obstruc-tion in the post-exercise period in asthmatic children.
In asthma the exact site of obstruction is not
known. Generally, asthma has been considered as a
disease of the small airways-airways beyond the
12th generation or those smaller than 2 mm in
dia-meter.’ However, with more severe obstruction or
during an asthmatic attack, in addition to the
ob-struction in the small airways (12th to 23rd
gener-ation), the large airways (1st to 12th generation)
become obstructed. In fact, Farr et aL’ have recently
reported that only large-airway obstruction is
pres-ent in some asthmatic patients. A mildly obstructive
process located in small airways can cause little
din-ical symptomatology, but more importantly only a
few pulmonary function tests can detect such an
abnormality. For this reason, Macklem’ regards
these peripheral or small airways as the “quiet zone.”
Exercise-induced bronchospasm (EIB) or
broncho-constriction after exposure to cold air, inert
irri-tants, allergens, and emotions may result in a variety
of responses in the airways. The full appreciation
of these airway responses will not be gained without
evaluating the airway changes in such a manner as
to be able to identify those patients with both
large- and small-airway changes as well as those
with only large- or small-airway changes. Further,
the parameters chosen to detect these changes
should be those least affected by effort.
Several techniques are available to detect
changes of airway caliber. These techniques are
listed in Table I. To demonstrate and compare the
sensitivity of these parameters, a study was
under-taken and is soon to be reported elsewhere.’
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S #{149} #{149} . . . S
5
,
_
baseline
0
10mm
10-15%
2.5-4.0 MPH
1.26
or 1.15 W/kg
BW
FIG. 1. Experimental protocol used in exercise tolerance testing.
%ot baseline
values
single
breath
N2 washout
200
180
160
140
body box
I
FVC
DRaw
a
FEV1
SGaw
0
MMEF
g
120
100
flcv
spirometry
peak flow
meter
80
7
30
1
30
1
30
1
30mm
EKG
pulse rate
clinical score
#{149}peak flow
FEV1, FVC,
MMEF
closing volume
airway
resistance
duration
inclination:
speed
work
I
40mm
FIG. 2. Relative sensitivities of different pulmonary function tests, reflecting airway
Fl.w
(v)
.3”
Flow
(V)
IV)
X-oxis
SUPPLEMENT
885
EXPIRAT ION
MEFV
wI_
FV-LOOP
a
(V)
x-a
x i
INSPIRATION
FIG. 3. Three different curves of the flow-volume relationships.
STUDY
I
Patients
and
Methods
Twenty-four bronchodilator-dependent asthmatic
boys, 8 to 14 years of age, were studied. Using a
mild or moderate standard work load for each,
several different pulmonary function parameters
after- exercise were compared. The experimental
protocol used is seen in Figure 1 which
demon-strates the parameters measured and the times
they were measured, as well as the duration of
ex-ercise. From top to bottom the pulse rate and ECG
were monitored during the times noted by the bars.
PEFR and clinical score were determined at the
appropriate time noted on the figure by the dots.
Forced vital capacity (FVC), forced expiratory volume
in one second (FEV,
),
airway resistance, (Raw),and closing volume (CV) were measured at baseline,
7 minutes after exercise, and 30 minutes after
ex-ercise. For an experimental work load, walking on
the treadmill was used. Walking represented an adequate physiological stress, and the work load
can be easily calculated when walking. On the
tread-mill, the patient ascends or carries his body weight
up a certain incline (% slope), for a certain distance
(number of revolutions-determined by the speed
and time). Changing any of these variables changes
the work load. A mild work load in young children
is performed when the pulse rate is increased to
145 to 165 beats per minute, whereas, at moderate
work load the pulse rate increases to 165 to 180
beats per minute. Since pulse rate in asthmatic
pa-tients appears to correlate linearly with oxygen
con-sumption,7 these loads correlated with 40% to 80%
of maximum aerobic power respectively. These
steady-state pulse levels are usually reached within
two or three minutes of the onset of exercise and
then this steady-state level is maintained throughout
the test unless the test is unduly long, and anaerobic
metabolism in the patients results in a metabolic
acidos is.
Results
and
Discussion
In Figure 2, we see changes in the seven
para-meters used in the above mentioned study; the
fol-lowing is evident. Results are expressed as a
percentage of baseline values. Note that each of the
paired parameters are shown at both 7 minutes
8nd 30 minutes after exercise. The vertical axis
represents the percent either below or above the
observed baseline value of IOO%. The greatest
change seen with these parameters was with CV,
followed by Raw, SGaw, parameters obtained
from spirometry (FVC, FEV1), and maximum
mid-expiratory flow rate (MMEF), and finally PEFR.
It is easy to see that the CV and Raw increased a
much greater amount than the FVC, FEV,, or PEFR
decreased. It also can be seen that PEFR, FVC, and
FEV1 illustrate a greater change at 7 minutes after
exercise than they do at 30 minutes. In fact, after
this work load, the PEFR is actually increased at 30
minutes despite the fact that the Raw and CV are still significantly increased.
For determination of CV, Antonisen et al.’s’
single-breath nitrogen washout technique was used.
However, out of 24 asthmatic boys, it was possible
to obtain complete CV data in only 5. In
determin-ation of CV the patient performs a maximal
expir-ation (to residual volume [RV]). Then, he takes a
deep breath of 100% oxygen (to maximal inspiration)
and expires his vital capacity (VC) as slowly and
evenly as he can. While he is expiring his air, the
percentage of nitrogen in that air and the volume
are being continuously measured and recorded. A
tracing of this maneuver plotting the percentage of
nitrogen in the air and volume of air expired (VC)
results in a curve with four different phases. Phase I
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Baseline
1mm
30mm
.69
12.2
.046
0G.
boy,
9 years
MMEF
.59
.31
Raw
8.0
11.5
SGaw
.018
.050
Fic. 4. Comparison of flow-volume relationships with
MMEF, Raw, and SGaw after exercise.
of this curve corresponds to the dead space. Phase
II is a transition to alveolar gas (dead space plus alve-olar gas). Phase III is the so called “alveolar plateau”
in which the nitrogen concentration shows a gradual
rise with well-marked oscillations of cardiac origin.
The sudden rise in this curve ends Phase III and starts
Phase IV and represents a steep rise in the nitrogen
concentration. This sudden increase in nitrogen
con-centration (junction of Phase III and IV) represents
the onset of Airway Closure. The single-breath
nitro-gen washout used in determination of CV depends on
the nitrogen present in the lungs at RV. During the
performance of a slow VC, it is the basal region of the
lungs which first “closes,” resulting in the rise of
ex-pired nitrogen concentration which comes from the
apical region. This method gives satisfactory results
in normal lungs and depends on a uniform
distribu-tion throughout the lung. Distribution of the air in the
lungs can be disturbed in a disease such as asthma,
and in this way a reading of CV in asthmatics is also
affected. In the five patients in the study, from whom
adequate tracings were obtained, the CV appeared
to be the most sensitive parameter reflecting airway
obstruction. However, the expected change in the
slope of the (alveolar) plateau (Phase IV) of the
nitro-gen washout curve which signals airway closure did
not appear except in the five subjects mentioned.
Some of the factors responsible for the abnormal
nitrogen washout tracing in the other 19 patients
(thus producing no sudden change in the [alveolar]
plateau) may be: non-uniform distribution of
venti-lation, abnormal respiratory flow patterns, local
changes in lung compliance (which can be
accen-tuated even more during exercise), and the inability
of the patients (especially after exercise) to hold
their breath at VC. All of the limitations of CV
deter-mination (nitrogen bolus technique) are not yet
known, but it certainly appears that CV is a
tech-nique best suited for detection of minimal or early
airway obstruction rather than severe or established
airway obstruction.
Considering the parameters felt to reflect changes
only in large airways, the parameters informing
us most about large airway caliber are SGaw and
Raw which are determined by body
plethysmo-graphy.” Since comparison of changes of Raw can
only be done at the same lung volume, the data
should be expressed as specific conductance.
SGaw Gaw
TGV
where TGV equals thoracic gas volume.
It can be seen in Figure 2 that airway resistance
was a sensitive indicator of airway obstruction but
became less sensitive when the Raw was compared
at the same lung volume (SGaw). There also were
individual cases when only these parameters
changed, but these were not frequent.
Flow rate determined during the mid-portion of
the spirometric tracing (MMEF) appears to be the
most effort-independent measure of airway
obstruc-tion. In addition, this parameter,3 unlike Raw or
SGaw, reflects obstruction localized in small
air-ways. In the presented study it also appears that
MMEF is one of the most sensitive parameters
re-flecting airway obstruction after exercise.
FVC is too effort-dependent and for adequate
re-producibility exhausts too many patients; however,
a decreased FVC as compared with a slow VC may
have value as an indirect reflection of trapped air
volume.
FEV1, like FVC, is also too effort-dependent and
likewise is not a very specific parameter. FEV,,
un-like MMEF, reflects not only small- but large-airway
obstruction as well as changes of airway
collapsi-bility and changes in elastic lung ;ecoil. Usually
when FEy, is significantly changed, airway
obstruc-tion can also be easily appreciated by the
stethescope.
FEV, percentage is controversial because not only
are both of the parameters used in its calculations
quite effort-dependent, but any unproportional fall
in the FVC and not in the FEV, could be falsely
in-terpreted as an improvement in the patient since
the FEV, percentage would be greater.
PEFR, reflecting both large- and small-airway
obstruction, is perhaps the most often used
tech-nique not only in exercise tolerance testing,”2 but
also in allergen provocation tests” and in long-term
follow-up of asthmatic subjects.12 Its convenience,
portability, and direct read-out make it extremely
advantageous from these points of view. However,
when PEFR was introduced by Wright and
McKerrow,’3’ its purpose was to provide a quick,
SUPPLEMENT
887
TABLE I
PARAMETERS DETERMINING AIRWAY OBSTRUCTION
Parameter Location Also Reflected
In Measurement
Anatomical Notes Clinical Notes
FVC Large and/or small
airways
Too effort-dependent
FEy1 Large and/or small
airways
Airway collapsability and
elastic lung recoil
Interlobar and segmental
bronchi (not very specific test
Often used;
effort-dependent
FEVI/FVC (FEV1%)
Large and/or small airways
PEFR Large and/or small
airways
Airway collapsability and elastic lung recoil
Not very specific for airway obstruction
Convenient; therefore most often used
SGaw Large airways Insensitive to measure
obstruction in small
1st to 12th generation of airways (very specific test)
Clinical correlation unknown; time-consuming
Raw Large airways 1st to 12th generation of
airways (very specific test)
Clinical correlation unknown;
time-consuming
MMEF Small airways 13th to 24th generation of
airways
Valuable; effort-independent
CV Small airways Disturbances in the
distribution of ventilation
Early airway obstruction (specific test)
Frequency-dependent compliance
Small airways Changes in lung
compliance
13th to 24th generation of airways (specific test)
Clinical correlation to be established
TAV Small airways Airway collapsability TGV (body box)-FRC (He)
(specific test)
Valuable
but it is not a specific test of lung function. More
importantly, PEFR is determined in the most
effort-dependent portion of the spirogram, and it is
mea-sured at variable lung volumes. The latter criticism
has further importance since, in a majority of
pa-tients, significant increases of TGV occur during
exercise-induced bronchospasm.”-” It has also been
suggested that PEFR may be produced to a large
extent by the sudden compression of the large
intra-thoracic airways occurring at the onset of a very
forced expiration. Further, it appears that as long
as there in an adequate VC even with significant
airway obstruction, with ample force or effort,’
a decent peak flow can usually be generated.
How-ever, because PEFR is so convenient, its
predomi-nent use by many investigators has delayed the
critical evaluation of the effects of exercise as well
as other stimuli in the asthmatic patient. More
sig-nificantly, PEFR is frequently used as the only
para-meter in identifying the acute and long-term effects
of drug therapy.” Thus, this may inhibit the
po-tential analysis of which airways are specifically,
or at least more specifically, affected by these drugs.
It would seem that just because tests have to be done
frequently to properly appreciate the effects of any
therapy, this should not prevent one from utilizing
more sophisticated techniques for the potential value
gained. As demonstrated in the reported study (Fig.
2), PEFR did not appear nearly as sensitive as other
pulmonary function tests.
Trapped air volume (TAV), although not shown on
Figure 2, may be a valuable technique yet to be
util-ized since its presence alone reflects abnormalities in
the airways, and it could be the only parameter seen
to change after exercise in some patients. However,
at present, the clinical implications of changes in the
TAV would be speculative but conceivably, since
in-creased trapped air is common after exercise, they
could be quite significant.
STUDY
2
Frequency-dependent compliance described by
Mead in 1969,” although reported to reflect changes
only in small airways, was not used in this study, nor
has it been reported as being used before and after
exercise. However, more recently described
para-meters used for detection of airway obstruction are
flow-volume relationships. Since expiratory flow is
not time-, but lung-volume-dependent, the
flow-volume relationships do gain value over the
conven-tional spirogram, because the flow rates are
dis-played simultaneously as the volume of the lung
de-creases, thus providing much more information
about the dynamic function of a patient’s airways.
For comparison, FEV, is merely the integration of all
of these flow rates. Flow-volume relationships can
be graphically obtained from the FVC maneuver.’0
However, more sophisticated and direct procedures
are presently used in order to obtain flow-volume
curves (wedge spirometer).
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Bass” has suggested the use of 25%, 50%, and 75%
of the VC to express flow rates and in such a way
analyze flow-volume relationships. It should be noted
that at 25% of the maximum expiratory flow-volume
curve (MEFV curve) flow values approach the value
for peak flow and at 50% of MEFV, flow values
ap-proach the value for MMEF; whereas, at 75% of the
MEFV, flow values approach the value for FEV’.
Ac-cording to Hyatt and Black,” one must dissociate the
flow-volume relationships (Fig. 3) into three
differ-ent types of curves (relationships) when volume
(V-liters) is plotted against flow (V-liters/sec).
(1) On the left we see the MEFV curve: This is a
plot of the maximal expiratory flow (V max) against
volume during the performance of an expiratory FVC
maneuver.
(2) In the middle of the figure we see what they
call the flow-volume curve: Here expiratory flow is
plotted against volume under conditions that differ
from those just mentioned.
(3) On the far right we see the flow-volume loop:
Here the maximal forced expiration and maximal
forced inspiration which are present on the same
graph make up the flow-volume loop.
The MEFV curve is a more reliable way of
study-ing expiratory flow events than is a spirogram
be-cause any reduction in expiratory flow at any given
volume is more readily visualized on the MEFV
plot than on a spirogram. The full value of these
relationships remain to be seen, but it is likely that
they may replace the conventional spirogram
es-pecially since MMEF can be determined from them
in addition to other valuable parameters.
PatIents
and
Methods
In an attempt to better understand the effects of
airway obstruction on the MEFV curve as well as to
compare these effects with the conventional
techni-ques of spirometry and body box, 16 asthmatic
sub-jects (9 to 12 years of age) were studied. Airway
ob-struction was again induced by exercise of a
mod-erate work load on the treadmill (2 w/kg of body
weight) in the manner previously described.
Also as before, the asthmatic subjects were tested
prior to the exercise and at 7 and 30 minutes after
exercise. The following pulmonary function tests
were studied: MMEF (measured by spirometry),
SGaw (measured by body plethysmograph), and
flow-volume parameters (measured by wedge
spiro-meter). Again the purpose was to compare in each
subject parameters obtained from the flow-volume
curve with MMEF and SGaw.
Results
and
DIscussion
When both parameters, MMEF and SGaw, were
decreased in the post-exercise period, significant
correlations were obtained between these “classical”
parameters and all of the flow-volume parameters.
However, when only one of these parameters was
decreased, no correlation could be obtained with any
of the flow-volume parameters. A typical example of
the changes just described is seen in Figure 4. It is
obvious that seven minutes after exercise significant
changes in all flow-volume parameters occurred. On
this figure you can see significant decreases in
vol-umes (y axis) and flow (x axis). Similarly, it is noted
that a significant decrease in MMEF and SGaw
occurred. Thirty minutes after-exercise the
flow-volume relationship re-approached the baseline
values as did MMEF. However, as can be seen, SGaw
and Raw are still significantly abnormal. This same
pattern was noted in eight of the 16 subjects tested.
It was thus concluded that under certain
circum-stances, the flow-volume curves reflect airway
ob-struction satisfactorily, but in other circumstances
they appear to be less sensitive than the “classical”
parameters.
COMMENTS
Finally, the relationships between more specific
pulmonary function parameters and clinical
situa-tions should be considered. It actually may be that
the reason some patients’ EIB is blocked by
atro-pine, others by 5% carbon dioxide,24 others by
iso-proterenol” or diethylcarbamazine pamoate,” and still
others by cromolyn,” is that the pathophysiology of
EIB is being seen in a more refined way than ever
before. Certain insults, such as emotions, cold air,
or inert irritants acting via the vagus” would more
selectively aggravate the large airways. Certainly,
atropine would be a great drug for some of these
patients, whereas 5% carbon dioxide might be
help-ful in others. If such patients were evaluated with
pulmonary function tests which reflected both small
and large airways, we might begin to realize why EIB
seems to have a variety of etiologies. EIB may even
be found to have different etiologies in the same
patients on different occasions, and this, too, could
be appreciated. Most importantly, however, certain
drugs acting via their receptor sites may be
dis-covered to be more effective for large airways than
for smaller, or vice versa. As you look over the
litera-lure, you see that nearly every anti-asthma drug has
at one time or another been evaluated by its ability
to prevent EIB. In agreement with the recent
state-ment by Godrey et al.’ we think exercise, since it is a
noninvasive technique, is the best tool we have for
evaluating the effectiveness of a drug and its
dura-tion of effect. However, the drug and perhaps the
patient are being “cheated” because the wrong
para-meter was evaluated. In selecting effective
therapeu-tics, for some patients we may need a “small-airway
drug,” for other, “a large-airway drug,” and for
some, probably most, a combination.
In conclusion, more information reflecting specific
pathophysiological changes for the patient may be
found if the airway obstruction is evaluated using the
best test available for selecting changes in the large
airways (SGaw) and the small airways (MMEF). In
this manner, not only may specific subgroups be
identified in the asthmatic population, but more
selective therapy may’ be found when presently
avail-able and new anti-asthma drugs are more carefully
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SUPPLEMENT
889
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