Spirometric assessment of lung transplant patients: one year follow-up.

Abstract

The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation.
Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections.
We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed.
The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) in comparison to the pre-transplant values (p <0.05). Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation.
The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery.
Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

Full text

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CLINICS 2009;64(6):519-25
CLINICAL SCIENCE
Disciplina de Cirurgia Torácica, Hospital das Clínicas da Faculdade de
Medicina da Universidade de São Paulo - São Paulo/SP,Brazil.
Email: paulopego@incor.usp.br
Tel: 55 11 3069-5351
Received for publication on January 07, 2009
Accepted for publication on March 03, 2009
SpIromEtrIC ASSESSmENt of LuNg
trANSpLANt pAtIENtS: oNE yEAr foLLow-up
Paulo M. Pêgo-Fernandes, Fernando Conrado Abrão, Frederico Leon Arrabal
Fernandes, Marlova L. Caramori, Marcos Naoyuki Samano, Fabio B. Jatene

doi: 10.1590/S1807-59322009000600006
Pêgo-Fernandes PM, Abrão FC, Fernandes FLA, Caramori ML, Samano MN, Jatene FB. Spirometric assessment of lung
transplant patients: one year follow-up. Clinics. 2009;64(6):519-25.
OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-
lung transplantation the first year after transplantation.
INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a thera-
peutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, im-
munosuppressive therapy and treatment of post-operative infections.
METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between
August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed.
RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung
transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1)
and the forced vital capacity (FVC) in comparison to the pre-transplant values (p <0.05).
Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant
difference in lung function beginning in the 3rd month after transplantation.
DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the
superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in
the double-lung group, this difference was no longer significant in the subsequent months after surgery.
CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to
greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved
lung function.
KEYWORDS: Lung transplantation; Spirometry; Respiratory function tests; Emphysema; Insufflation.
INTRODUCTION
Lung transplantation, which was initially described as
an experimental method in 1963, has become a therapeutic
option for patients with advanced pulmonary diseases due
to improvements in organ conservation, surgical technique,
immunosuppressive therapy and treatment of post-operative
infections.
In agreement with the International Society for Heart and
Lung Transplantation, the procedure is indicated for patients
with advanced chronic pulmonary disease without control
in spite of maximal medical therapy or for those for whom
there is no efficient medical treatment.1
Initially, pulmonary fibrosis was the only indication for
lung transplantation;2 however, indications have expanded
to include cystic fibrosis, primary and secondary forms of
pulmonary hypertension (PH), bronchiectasis and chronic
obstructive pulmonary disease (COPD), primarily of the
emphysema phenotype.3
Chronic obstructive pulmonary disease (COPD) is expected
to be the fifth leading cause of death in the world by 20204.
For many years, the only treatment that improved survival

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CLINICS 2009;64(6):519-25Spirometric assessment of lung transplant patients
Pêgo-Fernandes PM et al.
in patients with advanced COPD was chronic home oxygen
therapy.5,6 Since the 1990s, orthotopic lung transplantation has
proved to be an effective therapeutic alternative, although the
indication for this procedure is restricted by criteria of age, co-
morbidity, and feasibility of the surgery.7
There is a clear post-transplant survival benefit in patients
with advanced pulmonary fibrosis and PH. In patients with
cystic fibrosis and COPD a clear survival benefit has not
yet been demonstrated, but the post-transplantation gain in
quality of life and in physical activities tolerance appears to
be more important.8-12 We have also demonstrated that post-
transplantation bronchial stenosis can be corrected with a
self-expandable silicone stent.13
The lung transplant program at our institution began
in 1990. This program has experienced irregular patient
turnover and inactive periods. Between 1990 and 2003,
20 single-lung transplantations were performed. Between
2003 and 2007, when a permanent and exclusive team was
created, our institution performed 60 transplants. Of those 60
procedures, 36 were double-lung transplants. We performed
an annual mean of 15 transplants between 2006 and 2007.
When lung transplantation is indicated, a unilateral or
bilateral transplantation may be carried out. Single-lung surgery
maintains a native lung, whereas double-lung transplants require
the removal of both native lungs from the receiver.
Double lung transplant is a necessity for suppurative
diseases that attack both native lungs. In these cases, the
persistence of an infected lung in a transplanted individual
who needs immunosuppressive therapy can lead to infectious
exacerbations and risk of respiratory complications, such
as chronic sputum production and progressive physical
limitation after the operation.
Since the unilateral transplant technique is easier and
requires less surgical time, patients with non-suppurative
diseases like emphysema and pulmonary fibrosis often
initially undergo this procedure.14 However, even in
non-suppurative diseases, there seems to be prolonged
improvement when bilateral transplants are performed. For
example, in patients with COPD who underwent bilateral
lung transplantation, superior lung function and a trend
towards improved long-term survival were observed despite
apparent equity between the two methods when exercise
tolerance and quality of life were assessed.3,15
Since its initial description, the survival of lung
transplantation patients has increased. At present, some
centers report one-year survival in excess of 80%, with an
average of 60% survival after 3 years. With this increase
in life expectancy, it is important to study the methods of
follow-up and long-term control in order to quickly and
precisely diagnose infectious complications and rejection.16
Spirometry is used in the follow-up of transplanted
patients. The evaluation of FEV1 and FVC is a reproducible
method for screening for complications including rejection,
bronchiolitis obliterans and infection. This method has a low
diagnosis specificity regarding the type of complication.
In case of unilateral transplants, there is an additional
pitfall in the interpretation of spirometric data. An observed
decrease in FEV1 can be a consequence of complications in
the transplanted lung as well as progression of the disease or
hyperinsufflation in the native lung.
Decreases in FVC and FEV1 greater than 11% and
12%, respectively, are considered significant for bilateral
transplantation. In comparison, decreases in the FVC and FEV1
of greater than 12% and 13%, respectively, are considered
significant for unilateral transplantation. Such decreases
mandate investigation of rejection or infection of the organ.17
As noted previously, the surgical technique for bilateral
transplantation is more laborious than that for unilateral
transplantation. However, if this procedure presents long-
term advantages for the transplanted patient, this operation
is indicated. The advantages of bilateral transplantation
in patients with non-suppurative pulmonary diseases have
not been confirmed. Recent data show that spirometry
following double-lung transplantation is marginally superior
to that following single-lung transplantation in patients with
emphysema.18
The purpose of this study was to compare spirometry data
between patients who underwent single-lung and double-lung
transplantation at the first year after the transplant procedure.
We intend to determine whether bilateral lung transplantation
conveys a larger gain in pulmonary function and whether this
advantage persists after one year of follow-up. These results
will contribute to the growing evidence that bilateral lung
transplantation is superior to the unilateral alternative.
METHODS
We retrospectively reviewed the records of the 39
patients who underwent lung transplantation in our
institution between August 2003 and August 2006. Twenty-
nine of the patients survived to one year after surgery, and
all of them were followed. Another 10 patients (9 single-
lung transplantation and 1 double-lung transplantation) died
within the first post-operative year. These patients were
excluded from the study.
The follow-up after hospital discharge was carried out
weekly until the end of the third month, after which it was
conducted monthly or twice-monthly. In all visits, the patient
was evaluated by the performance of pulmonary function
tests, a radiological examination and blood tests.
The immunosuppressive therapy regimen used by our
group consists of induction with Basiliximab (Simulect)

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CLINICS 2009;64(6):519-25Spirometric assessment of lung transplant patients
Pêgo-Fernandes PM et al.
for suppurative patients and 1 gram of metilprednisolone
intraoperatively for all patients. The maintenance regimen
consists of tacrolimus, azathioprine and steroids. If the
patient is intolerant to tacrolimus, they receive cyclosporine
instead. In addition, azathioprine can be replaced with
mycophenolate mofetil. The standard treatment for acute
rejection is 10 mg/kg pulse therapy with metilprednisolone.
All patients underwent monthly vigilance bronchoscopies
for the first twelve months after transplantation. We collected
biopsies and bronchoalveolar lavage in order to identify
rejection and infections. After this period, the bronchoscopies
were performed according to clinical indication.
The spirometric values of these 29 patients who achieved
more than 1 year survival after lung transplantation were
analyzed. The FVC and FEV1 values were analyzed as the
percent of predicted value from the last test performed before
transplantation. These tests were performed at 1 month,
3 months, 6 months, 9 months and one year following
transplantation.
All spirometric measurements were carried out in
accordance with the guidelines of the International
Proceedings in Portable Spirometer (Koko Spirometry;
Pulmonary Data Services Instrumentation, Inc, Louisville,
Lap) or Pletsmograph (MedGraphics Elite Dx System, St
Paul, MN). The results are expressed in absolute values
and percentage of the predicted value using the equations
reported by Knudson et al.19 All tests were carried out in the
morning (Mondays from 8:30 to 11:30 am).20
The patients were divided into two groups according
to the type of lung transplant. The single-lung group
included 11 patients, and the double-lung group included
18 patients.
Each measurement passed a normality test (Kolmogorov-
Smirnov). The spirometric evolution of each group from pre-
transplant up to one year post-operation was compared using
analysis of variance (ANOVA). The comparative analysis
between unilateral and bilateral transplants at each time
point was performed by a students t-test for comparison of
averages. The value of significance was alpha = 0.05.
The sub-group of pulmonary emphysema patients (five
unilateral transplants and four bilateral transplants) was
analyzed separately with the same statistical methodology.
The statistical calculations were carried out by use of Sigma
Plot V10.0 (SPSS, Chicago, IL).
RESULTS
Demographic characteristics and lung function pre-
transplantation
The lung function of eighteen patients who underwent
bilateral lung transplantation and eleven patients who
received unilateral transplants were analyzed. Table 1
shows the baseline data of each group of patients. There
was a difference in the FVC and FEV1 on the pre-transplant
spirometry between unilateral and bilateral transplant
recipients (p=0.002 and p<0.001, respectively). The patients
who underwent double-lung transplantation had worse
lung function pre-transplantation. The FVC of transplanted
double-lung recipients was, on average, 14% less than in the
unilateral transplant group. The difference of the preoperative
FEV1 was 11%. The median age of the two groups was also
different; unilateral transplant recipients averaged 13 years
older than bilateral recipients (p=0.005).
Regarding the underlying disease, the single-lung
transplant group contained a higher number of pulmonary
fibrosis patients, while the double-lung transplant group
consisted of more patients with cystic fibrosis, bronchiectasis,
lymphangioleiomyomatosis and PH. Pulmonary emphysema
was the only condition with similar numbers of unilateral
and bilateral recipients in our cohort.
Post-transplant lung function evolution
Table 3 shows the mean values for FVC and FEV1
percent predicted in both single- and double-lung transplant
recipients during follow-up.
The increase in lung function in the double-lung transplant
group was more marked, showing a statistical difference from
the 1st month in both the FEV1 (Figure 1) and FVC (Figure
Table 1 - Demographic data of lung transplant recipients:
Single- vs. Double-lung transplant. (alpha = 0.05)
Single Lung
N=11
Double Lung
N=18

Sex 4F, 7M5F, 13M p = 0.694
Age (y)53.9 +/- 7.10 40.83 +/- 12.86 p = 0.005
Height (cm)160 +/- 9.06 164 +/- 8.0p = 0.206
Weight (Kg) 61.09 +/- 10.75 58.55 +/- 12.32p = 0.578
FVC % 54.27 +/- 7.70 40.23 +/- 12.45 p = 0.002
FEV1% 44.11 +/- 18.5923.68 +/- 9.18 p < 0.001
Disease p = 0.007
Emphysema54
Pulmonary Fibrosis61
Bronchiectasis 6
Cystic Fibrosis 5
Lymphangioleiomyo-
matosis
1
Pulmonary
Hypertension
1

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CLINICS 2009;64(6):519-25Spirometric assessment of lung transplant patients
Pêgo-Fernandes PM et al.
2) in comparison to the pre-transplant values (p <0.05). The
FVC of this group continued to increase during the first post-
operative year. We observed a significant increase between
the values in the 9th and 12th month as compared with the first
post-operative month (p <0.05).
In the single-lung transplant group, there was significant
increase of FVC after 3 months (p=0.002) and FEV1 after 6 months (p=0.004). After 3º and 6º months, the FVC and
FEV1 of the unilateral group did not vary significantly,
respectively.
Comparison of FEV1 and FVC post-transplant values (1,
3, 6, 9 and 12 months) between the unilateral and bilateral
transplant groups did not show any statistically significant
differences. Both groups improved from a functional point
of view.
The bilateral transplant group had a proportionally
higher gain since their pre-transplant lung function was
more compromised. In double-lung transplant recipients, the
FEV1 increased 3.75-fold from pre-transplantation values
at 12 months post-transplantation. By contrast, a 1.66-fold
increase was observed in the single-lung group over the
same period of time (p<0.001). The FVC increased 2.14-
fold in the bilateral group versus a 1.37-fold increase in the
unilateral group (p<0.001).
Sub-group of emphysema patients
During the period analyzed in our study, nine patients
Table 2 - Demographic data of lung transplant emphysema recipients: Single- vs. Double-lung transplant (alpha=0.05)
VariableTransplant PRE1 mo.3 mo.6 mo. 9 mo. 12 mo.
FVC Single55,71%** 65,55%73,99%*76,66%*79,01%* 77,37%*
Double 40,37%59,06%* 72,22%*76,10%* 81,64%*82,31%*
FEV1Single44,11%** 61,55%64,26%* 67,39%*70,86%*70,29%*
Double23,72%62,41%* 76,53%* 78,13%*82,17%* 85,41%*
Table 3 - Lung Function values in all single and double lung
transplant recipients during follow-up
Single Lung
N=5
Double Lung N=4
Sex 3F, 2M4M p = 1.000
Age (y) 52.2 +/- 8.1356.25 + / - 6.39 p = 0.444
Height (cm) 155 +/- 9.0 165 +/- 7.1p = 0.128
Weight (Kg)55.4 +/- 7.463.8 +/- 16.2p = 0.331
FVC %52.98 +/- 8.70 51.02 +/- 11.73 p = 0.781
FEV1%27.15 +/- 5.5821.08 +/- 4.75 p = 0.128
Values expressed in % predicted value. ** Statistically significant differ-
ence between single and double transplant groups. * Statistically signifi-
cant difference compared to pre-transplant values. Alpha = 0.05
Figure 1 - Forced vital capacity of lung transplant recipients (Single- vs.
Double-lung transplant group)
Figure 3 - Forced vital capacity of lung transplant recipients with emphysema
(Single- vs. Double-lung transplant group)

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Pêgo-Fernandes PM et al.
with pulmonary emphysema underwent pulmonary
transplantation, five single-lung and four double-lung
transplants. We compared the two techniques in this sub-
group of patients.
When the pre-transplant variables of each group were
compared, there was no observed difference in age, height,
weight or pulmonary function (Table 2).
Figures 3 and 4 show the evolution of the functional
data (FVC and FEV1) during the one year follow-up of the
emphysema patients subjected to lung transplantation. There
was no significant variation in the FVC in the unilateral
group during the post-transplant months in comparison with
pre-transplant values (p=0.861). For the same group, the
post-transplant FEV1 values increased from the sixth month
post-transplantation onwards (p=0.002). The double-lung
transplant group showed significant increases in FVC and
FEV1 from the third month post-transplantation onwards (p
<0.001 and p=0.002).
Comparisons between the two groups show a difference
in lung function beginning in the third month post-
transplantation. The unilateral transplant group had an
average FVC of 72.7 + 5.8% of the predicted value, and the
bilateral group had an average of 96.8 + 5.6% (p=0.001)
of the predicted value. This finding is reproducible when
comparing FEV1: the value for the unilateral group was 53.4
+ 15.1 % of predicted value and the value for the bilateral
group was 99.1 + 22.2% of the predicted value (p=0.015).
The difference in lung function between the groups was
maintained in all follow up measurements.
DISCUSSION
This study compared the spirometric evolution of single-
and double-lung transplant patients in the first year after
surgery. The results of the analyses of the whole group and
the sub-group of emphysema patients suggest the superiority
of bilateral transplantation over the unilateral alternative.
The values of the FVC and FEV1 pre-transplantation
were lower in patients who underwent double-lung
transplantation when compared to unilateral transplantation.
This difference is explained by the selection of younger
and more functionally impaired patients, such as those
with cystic fibrosis and bronchiectasis, for the bilateral
procedure.
Although the pre-transplant lung function values
were worse in the double-lung transplantation group, this
difference was not observed in the months following surgery.
After one year of follow-up, we observed an average 2.14-
fold gain in the initial value of the FVC and a 3.75-fold
increase in the FEV1 in bilateral transplant patients. By
contrast, we observed a 1.37-fold increase in the initial FVC
value and a 1.66-fold increase in the FEV1 in unilateral
transplant recipients. (P=0.004 and P=0.001, respectively).
Despite the initial disparities in lung function, we
demonstrated equality between the groups at one month
post-transplantation. This equality persisted through the
end of the first year. There were no statistically or clinically
significant differences between these groups. In summary, in
spite of worse initial lung function, double-lung transplant
patients exhibited functional performance, as measured by
spirometry, that was equal to or better than the single-lung
recipients during the observed period of follow-up.
Figure 2 - Forced expiratory volume in one second of lung transplant re-
cipients (Single- vs. Double-lung transplant group)
Figure 4 - Forced expiratory volume in one second of lung transplant recipi-
ents with emphysema (Single- vs. Double-lung transplant group)