PERSPECTIVE
LUNG TRANSPLANTATION
Duilio Divisi, MD, François Tronc, MD, Jean Paul Gamondes, MD.
Department of Thoracic Surgery, University Lyon Sud, L. Pradel Hospital,
Lyon-France.
 1. Brief Historical Overview
2. Indications Of Lung Transplantation
3. Contemporary Lung Transplantation: Results
4. Personal Experience
5. Management Of Problems In Lung Transplantation
Transplantation of organs is the great adventure of this century. Alexis Carrel
developed methods of joining blood vessels, which
made the transplantation of organs feasible. Demikhov
performed the first intra-thoracic canine lung
and heart transplantation in the 1940s. In the
early 1950s, Metras demonstrated that canine lung
transplantation is technical feasible. In 1963,
the first human lung transplant was performed
and during the subsequent 15 years, about 40 clinical
lung transplants were performed around the world.
Successful lung transplant was achieved in 1982.
The discovery of cyclosporine and its use as an
immunosuppressant drug permitted prolonged survival
in all transplanted organs especially in lung
transplants. At present, lung transplantation
is successfully used worldwide The remarkable
progress and improved results in lung transplantation
is due to superior immunosuppression strategies,
improved donor and recipient selection, new antibiotics,
improved strategies of preservation using prostaglandine
E1 have decreased reperfusion injury, and prevention
of post-operative sepsis due to bacterial, fungal,
viral and parasitic infections, especially in
cystic fibrosis. Heart-lung transplant is indicated
for patients with pulmonary vascular disease,
congenital heart disease and cystic fibrosis.
These represent 72% of indications. Double lung
transplant is reserved for bilateral lung anomalies
without consequences on cardiac function: infectious
diseases, bronchiectasies, cystic fibrosis, lymphangioleiomyomatosis,
bronchioloalveolar carcininoma, and emphysema.
Single lung transplant is reserved for patients
who have no infection of their native lungs such
as primary pulmonary hypertension without cardiac
insufficiency, idiopathic fibrosis, histiocytosis
X and emphysema without distension. The operative
mortality rate is in the range of 10%. The five-year
survival rate is about 60%. Despite advances in
treatment of complications such as infection and
chronic rejection, they are still responsible
for half of the deaths after transplantation.
However, in young patients with end-stage lung
disease, lung transplantation is the sole treatment.
(Heart Views. 2001;2(2): 53-56) © 2001 Hamad Medical
Corporation.
Key Words:
lung
transplant
pulmonary vascular disease cystic
fibrosis
cyclosporine
immunosuppression
Transplantation of organs is the great adventure of this century. In the first
half century, two surgeons, Carrel and Demikhov
and considered the Father (s) of Transplantation,
were responsible for the initial breakthroughs.
Carrel was ahead of his times. He developed methods
of joining blood vessels, which made the transplantation
of organs feasible. He advanced this technique
further and stimulated the use of transplantation
in experimental biology,conducting experiments
on reimplantation of limbs in dogs, transplantation
of organs and related vascularsurgery, which have
become common today. The importance of his primary
surgical work,the culture oftissue and organ preservation,
for which he was awarded the Nobel Prize in Medicine
in 1912, has not beenobscured by the passage of
time. Demikhov performed the first intra-thoracic
canine lung and heart transplantation in the 1940s.
In the early 1950s, Metras (1) demonstrated the
technical feasibility of canine lung transplantation.
In 1963, Hardy et al (2) reported the first clinical
lung transplant but the patient died after 18
days. During the subsequent 15 years, about 40clinical
lung transplants were performed around the world.
Derom et al (3) had the only patientdischarged
from the hospital eight months after lung transplantation.
The patient (a 23 -year-old male) died a short
time after as a result of sepsis, chronic rejection,
and bronchialstenosis. Subsequent development
of experimental canine lung transplantation enabled
a new technique of homolateral and bilateral lung
allografts (4). Successful lung transplant was
achieved in 1982. Reitz et al (5) reported their
clinical experience with heart-lung transplantation
(HLT) in patients with pulmonary vascular disease.
The Toronto Lung Transplantation Group (6) performed
the first unilateral lung transplant in a 58-year
old man with idiopathic pulmonary fibrosis, using
omentopexy, avoiding peri-operative corticosteroids.
Cyclosporine A discovered by Borel in 1978, has
impressive immunosuppression properties on T lymphocytes,
permitting prolonged survival in all transplanted
organs especially lung transplant. Subsequent
development of an experiment by Dark et al (7)
and clinical en bloc double-lung replacement technique
by Patterson et al (8) enabled bilateral replacement
of the lungs in patients for whom a single lung
transplant was not appropriate. But this replacement
needs a cardiac arrest and an extracorporeal circulation.
This complex procedure had clinical complications:
airway ischemia and cardiac denervation. Innovation
and technical advances have been achieved in a
simplified method of bilateral sequential lung
replacement: the “ bilateral single” lung transplantation
described by Bisson and Bonnette in 1992 (9).
Successive replacement of both lungs is usually
done by a horizontal thoracotomy in the 4th intercostal
space. This technique often avoids cardio-pulmonary
by-pass.
The indications are at present well established. HLT is indicated for patients
with pulmonary vascular disease, congenital heart
disease and cystic fibrosis. These represent 72%
of indications (10). Double lung transplant (DLT)
is reserved for bilateral lung anomalies without
consequences on cardiac function: infectious diseases,
bronchiectasies,cysticfibrosis lymphangioleiomyomatosis,
bronchioloalveolar carcininoma, and emphysema.
Single lung transplant (SLT) is reserved for patients
who have no infection of their native lungs such
as primary pulmonary hypertension (PPH) without
cardiac insufficiency, idiopathic fibrosis, histiocytosis
X and emphysema without distension. SLT is sometimes
very useful when there is only one suitable lung
donor.
At present, lung transplantation is successfully used worldwide. The registry
of the International Society for Heart and Lung
Transplantation was closed as of February 7, 1997.
This report represents data on 2186 HLT, 2543
DLT, 3939 SLT (10).
The remarkable progress and improved results in
lung transplantation is due to the following:
1) Superior immunosuppression strategies, improved
donor and recipient
selection, and new antibiotics.
2) Shortened donor bronchial lung reduces the
incidence of anastomotic
complications. Omentopexy
is no longer necessary.
3) Improved strategies of preservation using prostaglandine
E1 (PGE1), cold
extra-cellular pneumoplegia
(cold modified blood and low potassium
University of Wisconsin
solutions) have decreased reperfusion injury.
4) Prevention of post-operative sepsis due to
bacterial, fungal, viral and parasitic
infections, especially
in cystic fibrosis. These infectious complications
are
potentially fatal.
Appropriate matching
of donor and recipient CMV serology status and
the
prophylactic use of ganciclovir
markedly reducesinfectious complications.
The operative mortality
rate is in the range of 10%. The five-year survival
rate
is about 60%.
These improved results
are due also to improved management of problems
during and after transplantation.
But significant problems
remain, the most notably chronic pulmonary rejection
manifested by Bronchiolitis
Obliterans.
Methods
Between July 14, 1988 and February 14, 1996, 110 patients (F = 45 (41 %), M = 65 (59%),
mean age: 40 ± 15 years (1-64) underwent a primary transplant: 33 HLT, 22 DLT and 55 SLT.
Indications were:
 Vascular diseases (37 cases),
Infectious diseases (19 cases),
Emphysema (27 cases),
Miscellaneous (27 cases).
Results
Five patients required retransplantation (1 due to cardiac dysfunction and
4 due to Bronchiolitis Obliterans). In emphysema,
better functional results are observed in DLT
(FeV1/VC: 76 ± 17 %) than in SLT (FeV1/VC: 49
± 9 %) (p = 0,01). Cardiac output on exercise
is better after DLT (10,08 ± 01) than in SLT (7.8
± 18) (p = 0,04). Overall actuarial survival rates
after 1, 3, 5 years were respectively: 56, 4 +
4, 7%; 34, 4 + 4, 6% 29, 6 + 4, 6%. No difference
was noted between the 3 surgical techniques (p
= 0.53) or between HLT and SLT for PPH (p = 0.57).
There is no difference according to the age of
the recipient (p = 0.51) and the pathologies (p
= 0.32).
SLT is possible in primary pulmonary hypertension (PPH) without cardiopulmonary bypass (CPB).
Example:
A 40-year-old man with a history of primary portal hypertension presented with
12 months of progressive dyspnea. The diagnosis
of primary pulmonary hypertension was made on
the basis of clinical history and paraclinical
explorations.
Because of major esophageal varices, thrombocytopenia
(n = 70,000) and chronic fibrinolysis, a right
SLT without CPB was planned to minimize hemorragic
risk (CPB would have required 300 UI/kg of heparin).
During pulmonary artery clamping, the decrease
in cardiac index and the increase in pulmonary
vascular resistance can be tolerated provided
the O2 consumption is low and the right ventricular
perfusion pressure is maintained with combination
of PGE1 and epinephrine (11). In PPH, HLT does
not lead to better results when compared to SLT
since none of the functional parameters were significantly
different except for the resting pulmonary pressure
that was lower in HLT (14.3 ± 23 mmHg) than in
SLT (22.4 ± 5 mmHg) (12).
DLT is possible with good long-term result in bronchioloalveolar carcinoma (13).
Example:
A 41-year-old woman with history of smoking 20 packs of cigarettes a year was referred to our
institution for treatment of relapsing bronchioloalveolar carcinoma.
She had undergone left
inferior lobectomy in 1989.
She presented with dyspnea on mild exertion, chronic cough,
and massive bronchorrhea.
Clincal evaluation revealed limited extension of the carcinoma to both
lungs without adenopathy, and CT scans of abdomen and brain were negative for metastatic lesions.
These findings justified surgery. She underwent a DLT.
Typical bronchioloalveolar carcinoma wasobserved in the explanted lung.
Post-transplant, she experienced several complications:
Early stenosis of the right pulmonary artery was treated by balloon stent dilatation.
Bilateral bronchial stenosis was successfully treated by Gianturco expandable stents.
Aspergillus bronchitis occurred 5 months after transplantation and was successfully
treated with intravenous amphotericin infusion for 6 months.
She is living 6 years after transplantation. She has, however, resumed smoking
and developed severe depression, which has not
recurred over the last two years.
Airway complications were formerly a frequent cause of morbidity and mortality.
Superior preservation, improved sepsis prophylaxis,
and immunosuppression have reduced the incidence
of airway complications. No bronchial dehiscence
occurred in our series but out of a total of 132
anastomoses, 23 bronchial complications (stenosis
and bronchomalacia) occurred in 20 patients. They
have required the placement of a Gianturco endobronchial
stent. Indications were based on endoscopic and
spirometric data. The mean time between transplantation
and stenting was 5 ± 7.5 months. One lethal complication
(oesotracheal fistula) and six minor complications
resulted. The observed incidence of airway complications
does not justify in our opinion direct revascularization
of the bronchial arteries, considering the increased
operative morbidity and mortality associated with
this technique as reported in literature (14).
The evaluation of lung size is imprecise. Important differences of size between donor and
recipient are acceptable in lung transplantation. Strict criteria of equivalence were used.
We studied (15) the differences of total lung capacity (TLC) in the recipient (Helium dilution
and Plethysmography) and in the donor by Quanjer tables (16) in 44 patients. Significant
differences of size were sometimes observed with extremes: - 1800 ml, + 2300 ml without bad
outcome.
Pulmonary reperfusion edema delayed the closure of the chest in two cases.
The theoretical difference in TLC between donor and recipient are acceptable up to 2 litres.
Also we have to choose a donor’s lung whose theoretical TLC is between theoretical TLC and
plethysmography TLC of the recipient. Calculation of theoretical TLC is as follows:
For male
Theoretical TLC: [7.99 x length (meter)] - 7.08
For female Theoretical TLC: [6.60 x length (meter)]
- 5.78
A number of issues remain in lung-transplantation:
The necessity of using (CPB) in lung-transplantation.
There is a significant difference on survival during the first three years after transplant.
Best survival is remarkable when CPB is not necessary (p = 0.02).
CPB induces general inflammatory reaction characterised by neutrophile activation and its consequences.
The limitation of ischemia-reperfusion.
iinjury must be obtained by a good preservation technique using pneumoplegia with extracellular fluid with donor blood and prostaglandin E1 before and during pneumoplegia.
Infection and chronic rejection are the most frequent complications following lung
transplantation.
They are responsible for half of the deaths after transplantation. Despite
these complications, lung transplantation is the
sole treatment for young patients with end-stage
lung disease.
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Successful double lung transplantation for bronchioalveolar carcinoma.
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15. Bertocchi M, Mornex JF, Gamondes JP et al.D’importantes différences de
taille entre Donneur et Receveur sont acceptables pour les transplantations
pulmonaires.
Abstract Societé de Pneumologie de Langue Française 1992;
Strasbourg: 04-06 June.
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