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Função pulmonar e capacidade de exercicios em pacientes com tórax plano pós transplante pulmonar

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Pulmonary Function and Exercise Capacity
in Patients With Flat Chests After Lung
Transplantation
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Ryo Miyoshi, MD, Toyofumi F. Chen-Yoshikawa, MD, PhD, Akihiro Takahagi, MD,
Yohei Oshima, RPT, MS, Kyoko Hijiya, MD, Hideki Motoyama, MD, PhD,
Akihiro Aoyama, MD, PhD, and Hiroshi Date, MD, PhD
Department of Thoracic Surgery and Rehabilitation Unit, Kyoto University, Kyoto, Japan
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Background. Severe chest wall deformation is gener-
ally a contraindication for lung transplantation; however,
it is not known whether patients with flat chests have
reduced postoperative exercise capacity and pulmonary
function. This study’s purpose was to investigate the
relationship between preoperative thoracic shape and
postoperative exercise capacity and pulmonary function
in patients undergoing lung transplantation.
Methods. Twenty recipients who underwent successful
bilateral living-donor lobar lung transplantation were
evaluated. To analyze postoperative graft function in
relation to preoperative thoracic shape, 40 donor grafts
implanted into 20 recipients were divided into two
groups: flat chest group and normal chest group. Flat
chest is diagnosed when the thoracic anteroposterior
diameter to transverse diameter ratio is 1:3 or less.
Results. The ratio of the postoperative forced vital ca-
pacity to the preoperatively estimated forced vital ca-
pacity was significantly lower in the flat chest group than
Accepted for publication June 6, 2017.
Address correspondence to Dr Date, Department of Thoracic Surgery,
Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507,
Japan; email: hdate@kuhp.kyoto-u.ac.jp.
� 2017 by The Society of Thoracic Surgeons
Published by Elsevier Inc.
in the normal chest group 1 year after lung trans-
plantation (p[ 0.002). However, there were no significant
differences in postoperative 6-minute walk distances
between the two groups. Furthermore, the thoracic ante-
roposterior diameter to transverse diameter ratio in the
flat chest group significantly increased after lung trans-
plantation (p [ 0.02).
Conclusions. Although postoperative pulmonary func-
tion was significantly poorer for patients with flat chests
than for patients with normal chests, their postoperative
exercise capacity was equivalent. We also found that flat
chest severity significantly improved after lung trans-
plantation. Our study, the first investigating post-
operative functional status in patients with flat chests,
clearly shows that it is possible to perform lung trans-
plantation in such patients with acceptable outcomes.
(Ann Thorac Surg 2017;104:1695–701)
� 2017 by The Society of Thoracic Surgeons
iving-donor lobar lung transplantation (LDLLT) is an
Lestablished alternative for patients who cannot wait
for cadaveric lung transplantation [1–4]. Unlike cadaveric
lung transplantation, there can be large size discrepancies
between the donor and recipient because of the limited
population of potential LDLLT donors [5].
According to the International Society for Heart and
Lung Transplantation consensus for lung transplant
candidate selection, severe chest wall deformation is a
contraindication for lung transplantation because it can
cause severe restrictive pulmonary dysfunction after
transplantation [6]. However, patients referred as possible
candidates for LDLLT often show flat chests. Indeed,
patients with pleuroparenchymal fibroelastosis (a newly
defined idiopathic interstitial pneumonia subtype) tend to
have flat chests as a typical clinical characteristic [7, 8].
Regarding size matching, patients with flat chests may be
ideal candidates for LDLLT because only two lobes are
implanted. These patients may receive relatively over-
sized donor lung grafts, however, and may therefore be at
risk for graft compression.
Although we have previously reported trends for lung
graft function after LDLLT by preoperative graft size
matching [5], there are currently no reports investigating
these trends by thoracic shape. Therefore, we evaluated
the relationship between preoperative thoracic shape and
postoperative pulmonary function in bilateral LDLLT
recipients. We also investigated postoperative exercise
capacity and graft volume by preoperative thoracic shape.
Furthermore, we investigated changes in thoracic shape
after LDLLT.
Patients and Methods
Thirty-four bilateral LDLLT procedures were performed
at our institution between August 2008 and December
2014. Fourteen patients were excluded from the present
study: 5 underwent a special operative procedure, such as
native lung-sparing bilateral LDLLT [9]; 5 had significant
chronic complications, including bronchial stenosis and
severe kyphosis; and 4 could not undergo pulmonary
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function tests 1 year after LDLLT owing to death or severe
general condition. We performed a retrospective analysis
of the 20 remaining patients who underwent successful
transplantation with a total of 40 lower-lobe lung grafts.
The included recipients fulfilled the criteria for conven-
tional bilateral lung transplantation but were thought to
be too sick to wait for cadaveric lungs. All 40 donors met
the LDLLT donor criteria previously described [10]. The
study was approved by Kyoto University Hospital’s
Institutional Review Board (R0393). Written informed
consent was waived because of the study’s retrospective
nature.
With respect to size matching, we previously proposed
a formula for estimating graft forced vital capacity (FVC)
based on the number of segments in the graft [10–13]. The
right lower lobe contains five segments, the left lower
lobe four, and the whole lung 19, so we estimated graft
FVC as follows: Graft FVC ¼ measured right-donor
FVC � 5/19 þ measured left-donor FVC � 4/19. When
graft FVC was expected to exceed 45% of the recipient’s
predicted FVC, we accepted the size disparity regardless
of the recipient’s diagnosis.
We retrospectively reviewed pulmonary function test
results, 6-minute walk test results, chest computed to-
mography (CT) images, three-dimensional CT volumetric
data, and pulmonary ventilation scintigraphy for all do-
nors and recipients before LDLLT and 1 year after LDLLT
[14]. As noted, preoperative donor graft FVC and forced
expiratory volume in 1 second (FEV1) were estimated
according to the number of segments in the graft,
whereas each donor graft FVC and FEV1 after LDLLT
were assessed by the percentage of ventilation counts in
pulmonary ventilation scintigraphy [5, 11, 15]. The diffu-
sion capacity for carbon monoxide (DLCO) and DLCO/
alveolar volume (VA) were calculated with the same
method. The FEV1% was defined as FEV1/FVC.
Preoperative chest CT results from the 20 patients were
reviewed. To analyze postoperative graft function relative
to preoperative thoracic shape, 40 donor grafts (20 re-
cipients) were divided into two groups (flat chest group
and normal chest group) based on the diagnostic criteria
of straight back syndrome by DeLeon and colleagues [16]
(Fig 1). Flat chest is diagnosed when the ratio of the
anteroposterior thoracic diameter (measured at the T8
level) to the transverse thoracic diameter (measured at
the level of the diaphragm) on chest CT is 1:3 or less.
Patients were included in the flat chest group when this
ratio was 1:3 or less before LDLLT, and in the normal
chest group when the ratio was more than 1:3 before
LDLLT. We evaluated this ratio in all included patients at
each follow-up. We also evaluated thoracic shape using
three-dimensional CT.
Statistics
Continuous data are presented as mean � SD. Categoric
data are presented as number and group percentage.
Student’s unpaired t test and Fisher’s exact test were used
to identify significantbetween-group differences. Student
paired t test was used to identify significant differences
between specific timepoints. Data analysis was performed
using JMP, version 12 (SAS Institute, Cary, NC), and
p less than 0.05 was considered statistically significant.
Results
Recipients’ baseline characteristics are described in
Table 1. Ten patients (20 donor grafts) were assigned to
the flat chest group and the remaining 10 (20 donor grafts)
to the normal chest group. Patients in the flat chest group
had significantly lower body mass indexes before LDLLT
(p ¼ 0.03). Regarding the original diseases, half of patients
in the flat chest group had lung injury after hematopoietic
stem cell transplantation. The ratio of the thoracic ante-
roposterior diameter to transverse diameter in the flat
chest group was significantly lower than that in the
normal chest group before LDLLT (p < 0.0001). The
typical appearances of flat and normal chests are shown
in Figures 2 and 3, respectively.
Baseline characteristics of donor lung grafts are
described in Table 2. There were no significant differ-
ences in FVC size matching and three-dimensional CT
volumetric size matching between the flat and normal
chest groups (p ¼ 0.22 and p ¼ 0.73, respectively).
Table 3 and Figure 4 show function and graft volume in
the flat and normal chest groups before LDLLT and 1 year
after LDLLT. For technical reasons, DLCO was not
measured in patients with FVC values less than 1 L.
Notably, the ratios of the donor graft FVC to the preop-
eratively estimated FVC and of the donor graft FEV1 to
the preoperatively estimated FEV1 in the flat chest group
were significantly lower than those in the normal chest
group 1 year after LDLLT (p ¼ 0.002 and 0.03, respec-
tively; Fig 4A). Donor graft FEV1% in the flat chest group
was significantly higher than that in the normal chest
group 1 year after LDLLT (p ¼ 0.004).
There were no significant differences in the ratios of the
donor graft volume to the preoperatively estimated vol-
ume between the flat and normal chest groups 1 year
after LDLLT (p ¼ 0.13). However, the ratio of the donor
graft FVC increase to the donor graft volume increase in
the flat chest group was significantly lower than that in
the normal chest group 1 year after LDLLT (p ¼ 0.03).
In terms of exercise capacity, there were no significant
differences in 6-minute walk distances between the flat
and normal chest groups before LDLLT or 1 year after
LDLLT (p ¼ 0.79 and p ¼ 0.88, respectively; Fig 4B).
Moreover, there were no significant differences in body
mass index between the flat and normal chest groups 1
year after LDLLT (p ¼ 0.11).
Figure 5 shows changes in the thoracic anteroposterior
diameter to transverse diameter ratio in the flat chest
group and normal chest group. There was a significant
increase in this ratio in the flat chest group from before to
1 year after LDLLT (p ¼ 0.02).
Comment
The present study shows that postoperative pulmonary
function, as measured by FVC and FEV1, was significantly
lower in patients with flat chests than in patients with
Fig 1. The diagnostic criteria for flat
chest are based on the definition of
straight back syndrome by DeLeon
and associates [16]. On chest
computed tomography, the ante-
roposterior diameter “a” (left) was
defined as the distance from the
anterior border of T8 to the posterior
border of the sternum. The lateral
diameter “b” (right) was defined as
the transverse distance at the level of
the diaphragm. Flat chest was diag-
nosed when a/b was 1:3 or less.
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normal chests after bilateral LDLLT. However, exercise
capacity, represented by 6-minute walk distance, was
equivalent between groups after LDLLT. We also found
that flat chest shape severity was significantly improved
after LDLLT. Furthermore, donor lung grafts in the
normal and flat chest groups expanded beyond their
original sizes after LDLLT, but the ratio of the donor graft
FVC increase to the donor graft volume increase was
significantly lower in the flat chest group than in the
normal chest group after LDLLT.
Severe chest wall deformities, such as pectus excava-
tum, are known to cause restrictive pulmonary dysfunc-
tion [17]. Therefore, lung transplantation should be
performed carefully in patients with chest wall de-
formities because of the risk of poor functional outcomes.
Although several successfully performed lung trans-
plantations have been reported in patients with chest wall
deformities [18], these patients’ functional outcomes after
lung transplantation were not reported. Recently, pleu-
roparenchymal fibroelastosis was included as a new
category in the updated classification of rare idiopathic
Table 1. Preoperative Characteristics of Flat and Normal Chest G
Characteristics F
Age, years
Female
Height, cm
Weight, kg
Body mass index, kg/m2
Thoracic AP diameter to transverse diameter ratio, %
Indications for lung transplantation
Lung injury after hematopoietic stem cell transplantation
Interstitial lung disease
Others
Values are mean � SD or n (%).
AP ¼ anteroposterior.
interstitial pneumonias [7]. Therefore, the number of lung
transplantation candidates with pleuroparenchymal
fibroelastosis may increase in the future [7, 8]. Further-
more, a retrospective study reported that 75% of patients
undergoing lung transplantation for chronic graft-versus-
host disease after hematopoietic stem cell transplantation
showed pleuroparenchymal fibroelastosis in their
explanted lungs [19]. Patients with pleuroparenchymal
fibroelastosis tend to have restrictive pulmonary
dysfunction and flat chest shapes. Because of these
characteristics, the effect of lung transplantation on pa-
tients with pleuroparenchymal fibroelastosis is not fully
understood. Indeed, physicians who encounter patients
with flat chests due to pleuroparenchymal fibroelastosis
often question the recovery of functional status in these
patients after lung transplantation. Therefore, we con-
ducted the present study to assess the functional out-
comes after lung transplantation for patients with flat
chests.
Here, lung function values, such as FVC and FEV1, in
the normal chest group became greater than original
roups
lat Chest (n ¼ 10) Normal Chest (n ¼ 10) p Value
42.7 � 14.2 49.5 � 10.6 0.24
7 (70) 5 (50) 0.64
158.5 � 8.8 162.8 � 7.0 0.25
41.9 � 5.3 52.9 � 12.4 0.02
16.7 � 1.8 19.9 � 4.1 0.03
28.5 � 5.4 40.6 � 5.1 <0.0001
.
5 (50) 1 (10)
4 (40) 6 (60)
1 (10) 3 (30)
Fig 2. Typical appearance of chest
computed tomography (CT) before
and after lung transplantation. (A)
Preoperative chest CT image from an
18-year-old man with a flat chest
who had lung injury after hemato-
poietic stem cell transplantation. (B)
Chest CT image from the same pa-
tient 1 year after lung trans-
plantation, showing a significant
increase in the anteroposterior
thoracic diameter. (C) Preoperative
chest CT image from a 50-year-old
woman with a normal chest who had
interstitial lung disease. (D) Chest
CT image from the same patient 1
year after lung transplantation.
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estimates at 1 year after LDLLT, consistent with previous
findings [5, 11]. However, those values were significantly
lower in the flat chest group than in the normal chest
group, and they did not reach original estimates even at 1
year after LDLLT, although graft volume became more
than original estimates 1 year after LDLLT in both groups.
In contrast, exercise capacity was equivalent for both
groups 1 year after LDLLT. It is difficult to explain these
findings, but one major reason may be that flat chest
shape severity improved significantly after lung trans-
plantation. That is, improvements in flat chest shape
severity after lung transplantation may have increased
the efficiency of respiration during exercise. Even with
these improvements, postoperative maximallung func-
tion values were still lower in the flat chest group than in
the normal chest group 1 year after LDLLT, but patients
in both groups demonstrated similar exercise capacities.
Fig 3. Typical appearance of three-
dimensional computed tomography
(3D-CT) before (left panels) and after
(right panels) lung transplantation.
(A) Preoperative 3D-CT image from
an 18-year-old man with a flat chest
who had lung injury after hemato-
poietic stem cell transplantation. (B)
Three-dimensional CT image from
the same patient 1 year after lung
transplantation, showing a signifi-
cant improvement in flat chest shape
severity. (C) Preoperative 3D-CT
image from a 54-year-old man with a
normal chest who had interstitial
lung disease. (D) Three-dimensional
CT image from the same patient 1
year after lung transplantation.
These findings may address clinical questions related to
the postoperative functional recovery in patients with flat
chests, thereby helping physicians to actively refer such
patients to lung transplant centers. Furthermore, differ-
ences in body mass index, which was significantly lower
in the flat chest group preoperatively, became nonsig-
nificant after LDLLT. That might have been caused by the
decreased basal metabolic rate due to the increased effi-
ciency of respiration after LDLLT [20].
Three-dimensional CT volumetry has become increas-
ingly popular for assessing lung graft volume before and
after lung transplantation [14]. In preoperative three-
dimensional CT volumetric size matching, there were
no significant differences between the flat and normal
chest groups. Moreover, lung grafts in both groups
expanded beyond their original size after LDLLT. How-
ever, we found that the ratio of the donor graft FVC
Table 2. Preoperative Characteristics of Lung Grafts in Flat and Normal Chest Groups
Characteristics Flat Chest (n ¼ 20) Normal Chest (n ¼ 20) p Value
Donor graft FVC, mL 954 � 233 974 � 296 0.82
Donor graft FEV1, mL 803 � 198 810 � 243 0.93
Donor graft FEV1% 84.3 � 4.9 83.6 � 7.7 0.74
Donor graft DLCO 5.87 � 1.50 6.60 � 1.83a 0.18
Donor graft DLCO/VA 1.28 � 0.26 1.40 � 0.25a 0.17
Donor graft volume, mL 1,099 � 300 1,189 � 310 0.36
Recipient hemithorax volume, mL 1,050 � 531 1,192 � 575 0.42
FVC-based size matching, % 64 � 16 58 � 12 0.22
3D-CT volumetric size matching, % 123 � 53 117 � 46 0.73
a Data were available for 19 donor lung grafts.
Values are mean � SD.
DLCO ¼ diffusion capacity of lung for carbon monoxide; FEV1 ¼ forced expiratory volume in 1 second; FVC ¼ forced vital capacity; 3D-CT ¼
three-dimensional computed tomography; VA ¼ alveolar volume.
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increase to the donor graft volume increase in the flat
chest group was significantly lower than that in the
normal chest group 1 year after LDLLT. This finding in-
dicates that the efficiency of respiration in the flat chest
group was worse than that in the normal chest group
even after lung transplantation. Generally, in LDLLT, the
donor grafts produce lower FVC values compared with
the rates of volume increase partly because of topo-
graphic and mechanical issues that can result when the
lobe is not perfectly opposed to the chest wall [21]. Given
these issues in LDLLT, the graft FVC in the flat chest
group was more strongly affected by topographic differ-
ences between the donor graft and recipient hemi-
thoraces than that in the normal chest group. An
additional possibility is that lung function in the flat chest
Table 3. Functional Data of Recipients and Donor Grafts by Grou
Variables Group T
Ratio DG FVC to preop est FVC, % Flat chest
Normal chest
Ratio DG FEV1 to preop est FEV1, % Flat chest
Normal chest
Donor graft FEV1% Flat chest 84.
Normal chest 83.
Ratio DG volume to preop est volume, % Flat chest
Normal chest
Ratio DG FVC increase to DG volume
increase, %
Flat chest
Normal chest
Ratio DG DLCO to preop est DLCO, % Flat chest
Normal chest
Ratio DG DLCO/VA to preop est DLCO/VA, % Flat chest
Normal chest
6-minute walk distance, m Flat chest 216
Normal chest 231
Body mass index, kg/m2 Flat chest 16.
Normal chest 19.
DG ¼ donor graft; DLCO ¼ diffusion capacity of lung for carbon monoxide;
capacity; preop est ¼ preoperative estimated; VA ¼ alveolar volume.
group was affected by mechanical issues due to reduced
thoracic cage compliance. However, there are no objec-
tive methods for analyzing thoracic cage compliance itself
apart from the lung, so we compared chest CT results
before and after LDLLT. Although patients with flat
chests had some restrictions in chest movements before
and after LDLLT, we found that lung transplantation for
such patients was acceptable by showing clearly similar
postoperative exercise capacities for patients with flat
chests and normal chests. Development of an objective
method for evaluating thoracic cage compliance before
lung transplantation is essential for predicting post-
operative chest compliance in the future.
The limitations of our study include the single-
institution design, a relatively small sample size, and a
p
Before
ransplantation p Value
1 Year After
Transplantation p Value
100 (n ¼ 20) . 80.4 � 36.3 (n ¼ 20) 0.002
100 (n ¼ 20) 119.2 � 37.5 (n ¼ 20)
100 (n ¼ 20) . 87.1 � 36.6 (n ¼ 20) 0.03
100 (n ¼ 20) 117.0 � 47.5 (n ¼ 20)
3 � 4.9 (n ¼ 20) 0.74 92.7 � 9.3 (n ¼ 20) 0.004
6 � 7.7 (n ¼ 20) 81.2 � 14.0 (n ¼ 20)
100 (n ¼ 20) . 112.5 � 29.6 (n ¼ 20) 0.13
100 (n ¼ 20) 129.2 � 37.8 (n ¼ 20)
100 (n ¼ 20) . 72.3 � 32.8 (n ¼ 20) 0.03
100 (n ¼ 20) 94.6 � 22.4 (n ¼ 20)
100 (n ¼ 19) . 83.3 � 26.4 (n ¼ 13) 0.06
100 (n ¼ 20) 99.0 � 20.1 (n ¼ 20)
100 (n ¼ 19) . 156.2 � 43.7 (n ¼ 13) 0.22
100 (n ¼ 20) 175.7 � 44.7 (n ¼ 20)
� 119 (n ¼ 8) 0.79 483 � 147 (n ¼ 9) 0.88
� 106 (n ¼ 7) 474 � 114 (n ¼ 10)
7 � 1.8 (n ¼ 10) 0.03 17.4 � 3.2 (n ¼ 10) 0.11
9 � 4.1 (n ¼ 10) 20.1 � 3.8 (n ¼ 10)
FEV1 ¼ forced expiratory volume in 1 second; FVC ¼ forced vital
Fig 4. Donor graft forced vital ca-
pacity (FVC) and 6-minute walk
distance in the flat chest group and
normal chest group. (A) The ratio of
the donor graft FVC to the preoper-
atively estimated FVC in the flat
chest group (solid line) was signifi-
cantly lower than that in the normal
chest group (dashed line) 1 year after
lung transplantation (p ¼ 0.002). (B)
There were no significant differences
in 6-minute walk distances between
the flat chest group (solid line) and
normal chest group (dashed line)
1 year after lung transplantation
(p ¼ 0.88).
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relatively short follow-up period. The DLCO could not be
measured in some patients because of FVC values less
than 1 L. The assessment of function in each lung graft
rather than of overall pulmonary function in each patient
is also a limitation, although we assessed postoperative
lung graft function as precisely as possible using the
percentage of ventilation counts on pulmonary ventila-
tion scintigraphy [5, 11, 15]. To exclude the influence of
growth, we did not include patients whose heights
changed during the study period. Various original dis-
eases presented in both groups may also have imposed
an important limitation. For example, patients who had
lung injury after hematopoietic stem cell transplantation
(especially the restrictive type rather than the obstructive
type) often had flat chest shapes, which might be related
to pleuroparenchymal fibroelastosis being frequently
seen in these patients, as previously described [19]. These
disease-specific characteristics would likely affect the re-
sults of studies like ours. Moreover, the flat chest shapes
Fig 5. Changes in the thoracic anteroposterior diameter to transverse
diameter ratio in the flat chest group (solid line) and normal chest
group (dashed line). A significant increase was observed in the
thoracic anteroposterior diameter to transverse diameter ratio before
and 1 year afterlung transplantation in the flat chest group (28.5% �
5.5% and 32.0% � 7.0%, respectively; p ¼ 0.02). Alternatively, there
were no significant differences in this ratio before and 1 year after
lung transplantation in the normal chest group (40.6% � 5.1% and
38.7% � 7.3%, respectively; p ¼ 0.90). (NS ¼ not significant.)
of the patients in this study were the result of underlying
lung disease, not chest wall malformations.
Another important limitation in this study was that all
included patients underwent LDLLT, which is different
from the international trend, although the preoperative
measurement of donor graft function and volume was an
important advantage of LDLLT over cadaveric lung
transplantation. Because it would be difficult to measure
donor graft volume during the limited time before
cadaveric lung transplantation, lobar reduction could be
useful for patients with flat chests to avoid using over-
sized donor lung grafts. A preoperative comparison be-
tween the thoracic volumes of patients with flat chests
and the thoracic volume predicted by the height and sex
of patients without flat chests might also be helpful for
using properly sized donor lung grafts in cadaveric lung
transplantation for patients with flat chests. Therefore,
although we cannot measure actual donor graft function
preoperatively in cadaveric lung transplantation, a mul-
tiinstitutional study with a larger sample size including
patients undergoing cadaveric lung transplantation,
longer follow-up times, and patients with the same orig-
inal disease is warranted in the future.
In conclusion, in contrast to postoperative pulmonary
function, exercise capacity in patients with flat chests was
equivalent to that in patients with normal chests after
lung transplantation. We also found that the severity of
flat chest shape significantly improved after lung trans-
plantation. Our study is the first to investigate the post-
operative functional status in patients with flat chests. It
clearly shows that it is possible to perform lung trans-
plantation in such patients and obtain acceptable out-
comes for 1 year after the transplantation.
The authors wish to thank Dr Toshi Menju, Dr Toshihiko Sato,
and Dr Makoto Sonobe in the Department of Thoracic Surgery,
Kyoto University, for helpful discussions.
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	Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation
	Patients and Methods
	Statistics
	Results
	Comment
	References