723
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Patterns of dynamic hyperinflation during exercise
and recovery in patients with severe chronic
obstructive pulmonary disease
I Vogiatzis, O Georgiadou, S Golemati, A Aliverti, E Kosmas, E Kastanakis,
N Geladas, A Koutsoukou, S Nanas, S Zakynthinos, Ch Roussos
...............................................................................................................................
Thorax 2005;60:723–729. doi: 10.1136/thx.2004.039115
See end of article for
authors’ affiliations
.......................
Correspondence to:
Dr I Vogiatzis, National
and Kapodistrian
University of Athens Medical School, Thorax
Foundation, Centre for
Applied Biomedical
Research and Education,
106 75 Athens, Greece;
gianvog@phed.uoa.gr
Received
14 December 2004
Accepted 2 June 2005
Published Online First
17 June 2005
.......................
P
Background: Not all patients with severe chronic obstructive pulmonary disease (COPD) progressively
hyperinflate during symptom limited exercise. The pattern of change in chest wall volumes (Vcw) was
investigated in patients with severe COPD who progressively hyperinflate during exercise and those who
do not.
Methods: Twenty patients with forced expiratory volume in 1 second (FEV1) 35 (2)% predicted were
studied during a ramp incremental cycling test to the limit of tolerance (Wpeak). Changes in Vcw at the
end of expiration (EEVcw), end of inspiration (EIVcw), and at total lung capacity (TLCVcw) were computed
by optoelectronic plethysmography (OEP) during exercise and recovery.
Results: Two significantly different patterns of change in EEVcw were observed during exercise. Twelve
patients had a progressive significant increase in EEVcw during exercise (early hyperinflators, EH)
amounting to 750 (90) ml at Wpeak. In contrast, in all eight remaining patients EEVcw remained
unchanged up to 66% Wpeak but increased significantly by 210 (80) ml at Wpeak (late hyperinflators,
LH). Although at the limit of tolerance the increase in EEVcw was significantly greater in EH, both groups
reached similar Wpeak and breathed with a tidal EIVcw that closely approached TLCVcw (EIVcw/TLCVcw
93 (1)% and 93 (3)%, respectively). EEVcw was increased by 254 (130) ml above baseline 3 minutes after
exercise only in EH.
Conclusions: Patients with severe COPD exhibit two patterns during exercise: early and late hyperinflation.
In those who hyperinflate early, it may take several minutes before the hyperinflation is fully reversed after
termination of exercise.
rogressive dynamic hyperinflation leads to intolerable
sensations of breathlessness that make an important
contribution to the limitation of symptom limited
exercise in most patients with chronic obstructive pulmonary
disease (COPD).1 In these patients changes in end expiratory
lung volume (EELV) constitute an important outcome in
assessing the effects of therapeutic interventions on the
development of dynamic hyperinflation during exercise.2–4
The assessment of dynamic changes in EELV is routinely
carried out by serial inspiratory capacity (IC) manoeuvres5 6
assuming that, in patients with COPD, total lung capacity
(TLC) does not change appreciably during exercise.7 8
On the other hand, there are a significant number of
patients with COPD who do not hyperinflate progressively
during exercise6 9–12 but still claim dyspnoea as the main
cause of exercise limitation.6 The results reported for this
category of COPD patients are, however, discrepant as EELV
has either been reported to remain constant with increasing
intensity12 or actually to fall,11 as is commonly seen in healthy
subjects.13 Accordingly, exercise limitation in these patients is
not associated with end expiratory dynamic hyperinflation.
This implies that simply tracking changes in EELV during
exercise is not informative of all the factors that intensify
dyspnoea and reduce exercise capacity in these patients.
In COPD patients there is also variability in the response
of the end inspiratory lung volume (EILV) to exercise: most
studies report a progressive increase in EILV1 5 6 12 although
Aliverti et al11 found that some patients exhibit a stable
EILV. Assessment of all dynamically modified operational
lung volumes during exercise is therefore important for
understanding which factors contribute to exercise limitation. This study was undertaken primarily to identify possible
differences in the pattern of response in operational volumes
during exercise in patients with severe COPD.
Optoelectronic plethysmography (OEP) is a technique
capable of accurately measuring breath by breath changes
in the volumes of the entire chest wall (Vcw) and its rib cage
and abdominal chest wall compartments.13–15 In addition,
OEP can measure breath by breath variations in end
inspiratory and end expiratory Vcw and volume variations
of the different chest wall compartments. These measures are
crucial for understanding the different ventilatory strategies
adopted during exercise between different patients. OEP can
also track any changes in Vcw at TLC (TLCVcw) if maximal
inspirations are repeatedly made during exercise. Thus, one
can determine if tidal volume is restricted when end
inspiratory volume is at or near TLC. As the literature is
lacking research investigating changes in operational lung
volumes following the cessation of exhaustive exercise in
Abbreviations: EEVcw, end expiratory chest wall volume; EFL,
expiratory flow limitation; EIVcw, end inspiratory chest wall volume; EH,
early hyperinflator; fb, breathing frequency; FEV1, forced expiratory
volume in 1 second; FVC, forced vital capacity; FRC, functional residual
capacity; IC, inspiratory capacity; IRVcw, inspiratory reserve chest wall
volume; LH, late hyperinflator; OEP, optoelectronic plethysmography;
RER, respiratory exchange ratio; RV, residual volume; TLCO, carbon
monoxide lung transfer factor; TLC, total lung capacity; TLCVcw, chest
wall volume at total lung capacity; Vcw, chest wall volume; V̇E, minute
ventilation; V̇O2, oxygen uptake; VT, tidal volume; Wpeak, peak
workload.
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724
Subjects
The study patients included 15 men and 5 women with stable
COPD who satisfied the following criteria: (1) post-bronchodilator forced expiratory volume in 1 second (FEV1) ,50%
predicted and ratio of FEV1 to forced vital capacity (FVC)
,65% without significant reversibility (,12% change of the
initial FEV1 value); (2) optimised medical treatment; and (3)
no clinical evidence of exercise limiting cardiovascular or
neuromuscular diseases. Patients signed an informed consent
form and the protocol was approved by the University Ethics
Committee.
Pulmonary function assessment
Spirometric tests and measurement of lung transfer factor for
carbon monoxide (TLCO) were performed by a spirometer
(Masterlab; Jaeger, Wurzburg, Germany) while subdivisions
of lung volumes were measured by body plethysmography
(Medgraphic Autolink 1085D, Medical Graphics, St Paul,
MN, USA) according to ATS standards.16
Exercise protocol
The following incremental protocol was performed on an
electromagnetically braked cycle ergometer (Ergoline 800;
Sensor Medics, Anaheim, CA, USA): after 3 minutes of
measurements during quiet breathing, followed by 3 minutes
of unloaded pedalling, the work rate was increased every
minute (increments of 5 or 10 W) to the limit of tolerance
(Wpeak) while patients maintained a pedalling frequency of
60 rpm. The following gas exchange and ventilatory variables
were recorded breath by breath (Vmax 229, Sensor Medics):
oxygen uptake (V̇O2), carbon dioxide output (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), tidal
volume (VT), and breathing frequency (fb). Cardiac frequency (fc) and percentage oxygen saturation (SpO2%) were
determined using the R–R interval from a 12-lead on line
electrocardiogram (Marquette Max; Marquette Hellige
GmbH, Germany) and a pulse oximeter (Nonin 8600;
Nonin Medical, USA), respectively. The modified Borg scale17
was used to rate the magnitude of dyspnoea and leg
discomfort every 2 minutes throughout exercise.
Operational lung and chest wall volume
measurements
At baseline, during unloaded cycling and incremental
exercise, patients performed IC manoeuvres at quiet breathing, every 2 minutes during exercise, and in recovery.
Patients were instructed after 3–4 regular tidal breaths to
make maximal IC efforts from EELV to TLC according to
previously described methods.1 Simultaneously, chest wall
kinematics were measured by OEP as previously described.13–15
In brief, the movement of 89 retro-reflective markers
placed front and back over the chest wall from clavicles
to pubis was recorded. Each marker was tracked by six
video cameras (Smart System BTS, Milan, Italy), three in
front of the subject and three behind. Subjects grasped
handles positioned at the mid sternum level which lifted
the arms away from the rib cage so that lateral markers
could be visualised. Dedicated software reconstructs the
three-dimensional coordinates of the markers in real time
by stereophotogrametry and calculates total and compartmental chest wall volume and volume variations using
Gauss’s theorem. As in the study by Aliverti and coworkers,11 the chest wall was modelled as being composed of
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Comparison of OEP with spirometric data
VT measured by the OEP (VTOEP) was calculated as the
difference between end inspiratory and end expiratory Vcw
(EIVcw 2 EEVcw). As in a previous study15 in which we
assessed the ability of the OEP to measure changes in lung
volumes during exercise, we compared VTOEP with VT
obtained spirometrically (VTSP) over periods of 20 seconds
throughout all stages. IC was calculated by the OEP (ICOEP)
as the difference between TLCVcw and the EEVcw; the latter
value was derived by averaging the EEVcw over a period of
20 seconds before the IC effort (fig 1). ICOEP and EEVcw
values recorded at quiet breathing, during exercise and
recovery were compared with IC measured by the spirometer
(ICSP) according to previously described methods.1
Statistical analysis
Data are presented as mean (SE) values. Linear regression
analysis was performed using the least squares method. Two
way analysis of variance (ANOVA) with repeated measures
was used to identify statistically significant differences in
chest wall volumes across different time points between
groups. Within groups one way ANOVA with repeated
measures was performed to examine statistical differences,
followed by paired t tests when necessary. For all analyses a
statistical significance of 0.05 was used, with appropriate
Bonferroni corrections for multiple comparisons.
A
Quiet breathing
Peak exercise
22.0
TLC
TLC
Chest wall volume (l)
METHODS
two compartments—the rib cage and the abdomen. Vcw was
the sum of the rib cage volume (Vrc) and abdominal volume
(Vab).11 Vcw data are reported during quiet breathing,
unloaded cycling (0 Watts), at 33%, 66% and 100% of peak
exercise workload (Wpeak), and 1 minute (R1) and 3 minutes (R2) into the recovery.
21.5
Mean EI
21.0
20.5
Mean EI
20.0
19.5
Mean EE
Mean EE
0
70
360
460
Time (s)
B
26.0
Chest wall volume (l)
patients with COPD, we also investigated the pattern of
change in Vcw during recovery from exercise since this could
be an important issue for patients when dealing with
activities of daily living.
Vogiatzis, Georgiadou, Golemati, et al
25.5
TLC
TLC
Mean EI
25.0
24.5
Mean EI
24.0
23.5
Mean EE
0
70
Mean EE
340
400
Time (s)
Figure 1 Typical experimental tracings of absolute chest wall volume
measurements obtained from (A) an early hyperinflator and (B) a late
hyperinflator patient during quiet breathing and peak exercise. A
gradual shift in volumes during exercise occurred because of an increase
in mean end inspiratory (EI) and mean end expiratory (EE) chest wall
volumes indicated by the dashed line. Chest wall volumes at total lung
capacity (TLC) are indicated by an arrow.
Dynamic hyperinflation during exercise in COPD
725
Table 1 Mean (SE) demographic and post-bronchodilator data of the study population
and subgroups
Age (years)
Height (cm)
Weight (kg)
BMI (kg/m2)
FEV1 (l)
FEV1 (% pred)
FVC (l)
FVC (% pred)
FEV1/FVC (%)
TLCO (% pred)
TLC (% pred)
FRC (% pred)
RV (% pred)
IC (l)
IC (% pred)
COPD
(n = 20)
Early hyperinflators
(n = 12)
Late hyperinflators
(n = 8)
62 (2)
167 (2)
66 (2)
23.7 (0.7)
0.94 (0.07)
35 (2)
2.70 (0.13)
79 (4)
35 (2)
43 (6)
120 (22)
156 (14)
216 (10)
2.07 (0.08)
70 (4)
61 (3)
168 (3)
65 (3)
22.9 (1.0)
0.93 (0.10)
33 (4)
2.65 (0.19)
76 (5)
35 (3)
37 (4)
123 (13)
157 (11)
220 (12)
2.03 (0.12)
69 (7)
64 (2)
165 (3)
67 (4)
24.7 (0.7)
0.94 (0.09)
37 (7)
2.76 (0.15)
84 (5)
35 (3)
49 (13)
119 (16)
149 (10)
212 (9)
2.15 (0.08)
71 (5)
FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; TLCO, carbon monoxide lung transfer
factor; TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume; IC, inspiratory capacity.
RESULTS
Patient characteristics
Patients were characterised by severe airway obstruction and
a reduction in TLCO with increased TLC, functional residual
capacity (FRC) and residual volume (RV) (table 1). Exercise
capacity was severely compromised (table 2).
Comparison of OEP with spirometric data
The relationship between VTOEP and VTSP calculated simultaneously over a period of 20 seconds during quiet breathing,
exercise, and recovery is shown in fig 2. The linear regression
analysis yielded the following equation: VTOEP = 1.20VTSP 2
0.18 (r2 = 0.97, p,0.001). The mean percentage difference
between VTOEP and VTSP was 22.8 (1.2)% or 31 (14) ml. The
difference between the two systems at maximum workload
(100%peak) was 8.4 (4.5)% or 93 (17) ml, with the VTOEP
values being larger.
Changes in IC from quiet breathing measured by the
spirometer (DICSP) were in good relationship with the EEVcw
calculated by the OEP (DEEVcwOEP) during exercise and
Table 2
recovery (fig 3A). Linear regression analysis provided the
following equation: DEEcwOEP = 0.82DICSP + 0.03
(r2 = 0.91, p,0.001). The mean percentage difference
between DEEcwOEP and DICSP throughout all stages was
7.0 (5.8)% or 35 (24) ml.
In addition, a close correlation was found between ICOEP
and ICSP during all stages (fig 3B). Linear regression analysis
provided the following equation: ICOEP = 0.65ICSP + 0.52
(r2 = 0.89, p,0.001). The mean percentage difference
throughout all stages between ICOEP and ICSP was 3.8
(1.8)% or 73 (32) ml.
Changes in operational Vcw during exercise and
recovery
Two significantly different patterns of change in EEVcw were
observed during exercise in our patients (fig 4). Twelve
patients exhibited a progressive significant increase in EEVcw
during exercise (early hyperinflators, EH) amounting to 750
(90) ml at Wpeak (fig 4A). In contrast, in all eight remaining
patients EEVcw remained unchanged from quiet breathing
Mean (SE) peak exercise data of the study population and subgroups
Wpeak (Watt)
Wpeak (% pred)
Exercise tolerance (min)
V̇O2 (l/min)
V̇O2 (% pred)
RER
fc (beats/min)
fc (% pred)
SpO2 (%)
V̇E (l/min)
VT (l)
fb (breaths/min)
Dyspnoea (Borg)
Leg fatigue (Borg)
DEIVcw (l)
DEEVcw (l)
VTOEP/ICOEP (%)
IRVcw (l)
IRVcw/TLCVcw (%)
COPD
(n = 20)
Early hyperinflators
(n = 12)
Late hyperinflators
(n = 8)
45 (4)
37 (3)
6.7 (0.4)
0.83 (0.06)
50 (4)
1.06 (0.05)
115 (2)
73 (2)
92 (1)
30.8 (2.0)
1.24 (0.08)
26 (2)
4.1 (0.3)
4.1 (0.3)
0.97 (0.10)
0.53 (0.09)
86 (2)
0.19 (0.04)
7 (1)
44 (7)
34 (4)
6.4 (0.5)
0.81 (0.09)
47 (5)
1.08 (0.02)
114 (4)
72 (2)
93 (2)
31.1 (2.6)
1.22 (0.10)
26 (3)
4.1 (0.5)
4.3 (0.3)
1.17 (0.17)
0.75 (0.09)
88 (2)
0.14 (0.05)
7 (1)
47 (5)
40 (5)
7.2 (0.6)
0.84 (0.08)
53 (7)
1.07 (0.07)
116 (5)
75 (5)
91 (1)
30.1 (2.7)
1.28 (0.12)
25 (2)
3.6 (0.3)
3.4 (0.7)
0.66 (0.08)*
0.21 (0.08)*
83 (6)
0.26 (0.08)
7 (3)
Wpeak, peak workload; V̇O2, oxygen uptake; RER, respiratory exchange ratio; fc, cardiac frequency; V̇E, minute
ventilation; fb, breathing frequency; EIVcw, end inspiratory chest wall volume; EEVcw, end expiratory chest wall
volume; IC, inspiratory capacity; OEP, optoelectronic plethysmography; IRVcw, inspiratory reserve chest wall
volume; VT, tidal volume; TLCVcw, chest wall volume at total lung capacity.
D indicates changes from quiet breathing.
*Significant differences between groups.
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Vogiatzis, Georgiadou, Golemati, et al
1.4
0.8
1.2
0.6
∆EEVcwOEP (l)
VTOEP (l)
726
1.0
0.4
0.2
0.8
0.6
0.6
A
0.8
1.0
1.2
0.0
0.0
1.4
0.2
Figure 2 Regression line between tidal volume (VT) from the spirometer
(VTSP) and optoelectronic plethysmography (VTOEP) during quiet
breathing, exercise, and recovery. Each point represents the mean value
of all 20 patients. Line of identity is also shown.
2.2
up to 66% Wpeak (fig 4B). In the latter group, however,
EEVcw was significantly increased by 210 (80) ml compared
with quiet breathing at Wpeak (late hyperinflators, LH). The
two groups also differed in terms of the recovery pattern: in
the EH group EEVcw was still 254 (130) ml higher at
3 minutes into the recovery period than at quiet breathing
while, in the LH group, the EEVcw had returned to the level
at quiet breathing within 3 minutes of the recovery (fig 4).
In the EH group TLCVcw increased, albeit not significantly,
compared with quiet breathing from 66% Wpeak onwards
(fig 4). At Wpeak the increase in TLCVcw from quiet
breathing amounted to 198 (95) ml, corresponding to an
increase of 0.8 (0.1)% of TLCVcw measured at quiet breathing. At 1 minute of recovery TLCVcw was still higher than
during quiet breathing (by 153 (64) ml), whereas by
3 minutes of recovery TLCVcw had reached values very close
to quiet breathing (fig 4). Similarly, in the LH group, TLCVcw
increased by 72 (25) ml at Wpeak (0.3 (0.1)% of TLCVcw at
quiet breathing) but it did not differ significantly from that
recorded during quiet breathing (fig 4).
The pattern of change in EIVcw during exercise did not
differ between the groups. EIVcw increased significantly
throughout exercise and remained significantly higher than
quiet breathing during recovery (fig 4). At Wpeak patients in
both groups breathed with a tidal EIVcw that closely
approached TLCVcw (table 2), thus restricting further
expansion of VTOEP. During exercise, V̇E and VTOEP in the
EH group tended to be higher than in the LH group.
Nevertheless, volume constraints on VTOEP expansion
(VTOEP/ICOEP, IRVcw/TLCVcw) were similar between the
groups, whereas IRVcw reached the same level in both
groups (table 2). Symptoms of dyspnoea and leg discomfort
did not differ between the groups. Neither resting lung
volumes, peak exercise workload, nor gas exchange were
significantly different between the two groups (tables 1 and
2).
1.8
Compartmental tidal volumes
The volume variations for the abdominal compartment were
significantly different between groups during exercise and
recovery (fig 4 middle panels). In the EH group the increase
in EEVcw with increasing work rate was almost entirely
attributable to the significant increase in end expiratory Vrc
with no significant contribution from Vab (fig 4, top left and
middle panels). In contrast, in the LH group there was no
significant change in EEVcw up to 66% Wpeak; this was
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0.4
0.6
0.8
∆ICSP (l)
VTSP (l)
B
ICOEP (l)
2.0
1.6
1.4
1.2
1.2
1.4
1.6
1.8
2.0
2.2
ICSP (l)
Figure 3 (A) Regression line between volume changes from quiet
breathing in inspiratory capacity measured by the spirometer (DICSP)
and end expiratory chest volume calculated by optoelectronic
plethysmography (DEEVcwOEP) throughout all stages. Each point
represents the mean value of all 20 patients. (B) Regression line between
the inspiratory capacity measured by the spirometer (ICSP) and the
inspiratory capacity calculated by the optoelectronic plethysmography
(ICOEP) at quiet breathing, during exercise and recovery. Each point
represents the mean value of all 20 patients.
attributed to the significant decrease seen in end expiratory
Vab during exercise (fig 4, bottom middle panels). In the EH
group VTOEP expansion was due to a progressive increase in
end inspiratory Vrc and Vab whereas in the LH group the
increase in VTOEP was achieved by an increase in end
inspiratory Vrc and a decrease in Vab (fig 4).
In both groups, 3 minutes into recovery VTOEP remained
significantly higher than at quiet breathing, mainly as a
result of increased end inspiratory Vrc in both groups. In
contrast, within 3 minutes of recovery the end expiratory Vrc
in both the EH and LH groups was not significantly different
than at quiet breathing.
Throughout incremental exercise sensations of dyspnoea
and leg discomfort tended to be higher in the EH group than
in the LH group (fig 5). However, the differences between the
groups were not significant.
DISCUSSION
The main findings of this study are:
N
In patients with severe COPD there are two distinct
patterns of change in the chest wall volume response to
exercise: in the EH group EEVcw progressively increases
throughout exercise while in the LH group it remains
Dynamic hyperinflation during exercise in COPD
727
Rib cage
A
Abdomen
Chest wall
2.5
Volume (l)
2.0
1.5
EH
1.0
0.5
†
0.0
_
0.5
B
2.5
Volume (l)
2.0
1.5
LH
1.0
0.5
0.0
†
†
_
0.5
QB
0
33 66 100 R1 R2
QB
Workload (%peak)
0
33 66 100 R1 R2
Workload (%peak)
QB
0
33 66 100 R1 R2
Workload (%peak)
Figure 4 Volumes of the rib cage and the abdominal compartments and of the total chest wall in (A) early hyperinflators (EH) and (B) late
hyperinflators (LH) expressed in absolute values during quiet breathing (QB), exercise, and recovery (R1 and R2). Open circles indicate end of
inspiration; closed circles indicate end of expiration; triangles indicate chest wall volumes at total lung capacity. ÀSignificant differences in time points
between groups.
N
N
unchanged up to 66% Wpeak, but increases significantly at
Wpeak.
Although at the limit of tolerance the increase in EEVcw
was significantly greater in the EH than in the LH group,
both reached similar values of Wpeak, IRVcw and
dyspnoea.
Groups did not differ in terms of resting lung volumes or
exercise tolerance measures.
5
A
Dyspnoea (Borg)
4
3
2
1
0
Leg fatigue (Borg)
5
B
4
3
2
1
0
QB
0
33
66
100
Workload (%peak)
Figure 5 Perceptions of (A) dyspnoea and (B) leg discomfort at quiet
breathing (QB) and during exercise between early (closed symbols) and
late hyperinflators (open symbols).
N
After exercise the EEVcw did not return to the pre-exercise
value by 3 minutes in the EH group.
In healthy subjects, in whom expiratory flow limitation
(EFL) is absent, EELV decreases progressively during
exercise.13 15 In contrast, the progressive increase in EELV
that is typically observed in patients with severe COPD during
exercise is mainly dictated by EFL.12 18 Koulouris and
colleagues12 have shown that if EFL is present during resting
breathing, any further increase in ventilation during exercise
is associated with progressive dynamic hyperinflation. The
progressive increase in EEVcw observed in the EH group (12
patients) with increasing exercise level presumably reflects
the presence of EFL already at rest. On the other hand, eight
patients exhibited hyperinflation only at Wpeak. This
suggests that in these subjects EFL started only after 66%
Wpeak, in line with previous findings12 which indicated that
some COPD patients do not reach EFL up to two thirds of
Wpeak. Furthermore, it should be noted that in our LH
patients, the end expiratory Vab decreased progressively in
the range of 0–66% Wpeak. The decreased end expiratory Vab
during exercise reflected increased abdominal muscle activity. It has been postulated that such a contraction is
beneficial because of lengthening of the diaphragm resulting
in improved generation of a negative pleural pressure (better
position of the length-tension relationship).19 20 Although,
end expiratory Vab was reduced over this exercise range,
EEVcw did not change as there was a simultaneous increase
in end expiratory Vrc.
Aliverti et al11 have also reported that not all patients with
COPD hyperinflate during exercise. They studied 20 patients
during incremental exercise: 12 were EH similar to the
present study, while in eight the EEVcw actually decreased
from early exercise. These subjects were, however, different
from the LH subjects of the present study and those of
Koulouris et al.12 Their FEV1 averaged 50% of predicted
compared with our value of 37%, and their exercise
performance was very poor with a Wpeak of only 20 W
compared with 40 W in the LH group. In the present study
the overall group of patients is comparable, at least in terms
of FEV1, to that reported by Aliverti et al11 for the
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728
hyperinflators (having an FEV1 of 39% predicted). This is
probably the reason why we were not able to identify any
‘‘euvolumic’’ patients as described by Aliverti et al.11
Furthermore, there were important differences in chest
wall kinematics in their non-hyperinflators11 compared with
our LH group. They found no increase in EIVcw as exercise
workload increased and hence the increase in VTOEP during
exercise was solely due to the decrease in EEVcw, presumably
reflecting absence of EFL throughout exercise. In addition, at
Wpeak there was a large IRVcw amounting to approximately
1.3 l, while in our subjects it was only 0.26 l. Neither
Koulouris et al12 nor O’Donnell et al6 found patients with
such a high inspiratory reserve volume at the limit of
tolerance as Aliverti et al.11 In our study VTOEP increased with
exercise entirely by an increase in EIVcw so that, at Wpeak,
EIVcw was very close to TLCVcw and IRVcw was minimal.
We found no decrease in EEVcw and the decrease in end
expiratory Vab was considerably less than in their patients. It
is therefore possible that, besides the different degree of EFL
experienced by patients in the two studies, expiratory muscle
recruitment was more in their patients than in ours, leading
to a greater work of breathing.
Accordingly, when the findings of the present study are
compared with those of Aliverti et al,11 it can be suggested
that, during the natural history of COPD, patients pass
through a stage with moderate impairment of expiratory flow
rates so that exercise does not impose dynamic hyperinflation. With further disease progression, manifested by
decreasing FEV1, dynamic hyperinflation might be accompanied by lesser degrees of expiratory muscle recruitment
and increased dynamic hyperinflation. Longitudinal studies
will be required to determine if this hypothesis is correct.
The present study provides, for the first time, simultaneous
changes in Vcw at the end of inspiration, expiration, and at
TLC during symptom limited exercise in patients with severe
COPD. Interestingly, at Wpeak tidal EIVcw closely
approached TLCVcw in both EH and LH. Accordingly,
exercise limitation was associated with the fixed mechanical
constraint set by the reduced IRVcw rather than the
magnitude of the change in EEVcw per se. The increase in
dynamic hyperinflation during exercise is therefore not the
only mechanism limiting exercise capacity in patients with
severe COPD.
We also observed that TLCVcw in both EH and LH
increased at Wpeak from quiet breathing, albeit not
significantly (EH: by 198 (95) ml or 0.8 (0.1)% of TLCVcw
measured during quiet breathing; LH: by 72 (25) ml or 0.3
(0.1)% of TLCVcw measured during quiet breathing). The
magnitude of these changes in TLCVcw in both groups during
exercise is in agreement with previous suggestions that small
changes in TLC may occur during exercise because hyperinflation can cause an increase in lung distensibility.21–23
Accordingly, changes in TLCVcw tended to be larger in EH,
possibly because they were more hyperinflated than the LH.
It should be noted, however, that changes in chest wall
volumes include changes in gas volume, gas compression,
and blood volume.13 The progressive increase in TLCVcw seen
in both groups could therefore be the result of all of these
factors, which may in turn explain, at least in part, the small
discrepancies found between the changes in volumes
recorded at the mouth by the spirometer and those calculated
from the chest wall signals (figs 2 and 3).
In the EH group EEVcw was increased by 254 (130) ml
above baseline 3 minutes after exercise. This is in agreement
with that recently reported by O’Donnell et al24 who found
that IC 3 minutes into recovery from symptom limited
exercise was greater by 250 (35) ml than at baseline. The
present study extends these findings by showing that, in the
EH group, the greater degree of dynamic hyperinflation and
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Vogiatzis, Georgiadou, Golemati, et al
air trapping during exercise should have enhanced the
threshold loading mainly of the muscles of the rib cage
compartment so that during recovery the function of these
muscles would take longer to return to baseline.
Furthermore, the delayed recovery of dynamic hyperinflation
has important clinical implications when designing rehabilitative exercise training regimes for patients with severe
COPD, especially if high intensity interval exercise is
chosen.25 26
In conclusion, we found that patients with severe COPD
fall into two groups: those who hyperinflate early in exercise
and those who hyperinflate late. Despite this different
pattern, exercise capacity is similar, probably reflecting the
fact that both groups closely approached their TLC at Wpeak.
.....................
Authors’ affiliations
I Vogiatzis, O Georgiadou, S Golemati, E Kosmas, E Kastanakis,
A Koutsoukou, S Nanas, S Zakynthinos, Ch Roussos, National and
Kapodistrian University of Athens, Department of Critical Care Medicine
and Pulmonary Services, Evangelismos Hospital, ‘‘M Simou and G P
Livanos Laboratories’’, Athens, Greece
I Vogiatzis, O Georgiadou, N Geladas, Department of Physical
Education and Sport Science, Athens, Greece
A Aliverti, Dipartimento di Bioingegneria, Politecnico di Milano, Milano,
Italy
This work was supported by the European Community CARED FP5
project (contract n. QLG5-CT-2002-0893) and by the Thorax
Foundation.
Competing interests: none declared.
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LUNG ALERT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Is adjuvant chemotherapy for non-small cell lung cancer here to stay?
m Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs observation in resected non-small cell lung cancer.
N Engl J Med 2005;352:2589–97
I
n this study patients with completely resected stage IB or stage II non-small cell lung
cancer were randomised to either adjuvant chemotherapy with vinorelbine and cisplatin
(n = 242) or to observation (n = 240). The primary end point was overall median survival
which was significantly prolonged in the chemotherapy group (94 v 73 months; adjusted
p = 0.04). This corresponds to an overall survival advantage at 5 years of 15 percentage
points (p = 0.03). Fewer patients in the chemotherapy group had disease recurrence (36.0%
v 49.6%, p = 0.003). While subgroup analysis of stage IB patients did not show a significant
improvement in survival, the overall analysis showed disease stage not to be a significant
predictor of treatment effect. Improved survival was associated with chemotherapy and
squamous histology, whereas shorter survival was associated with older age, male sex, and
pneumonectomy compared with lesser resection. Side effects from chemotherapy were seen
in many patients, but in comparable numbers to other reports: there were two deaths (0.8%)
and febrile neutropenia was documented in 7%.
This study has continued the recent trend of showing survival advantage with adjuvant
chemotherapy and demonstrates a greater benefit than previous reports. This may be due to
the sole use of a modern chemotherapy regimen compared with previous studies. Is
adjuvant chemotherapy now to be considered the standard of care for such patients
undergoing complete resection? Probably, although further work should be done to
delineate which patients are likely to obtain the greatest benefits while hopefully avoiding
the severe morbidity which can be associated with chemotherapy.
T J Warke
Consultant Respiratory Physician, Royal Victoria Hospital, Belfast, UK;
tim@dsl.pipex.com
www.thoraxjnl.com