LUNG TRANSPLANTATION
Clinical lung transplantation was first attempted in the 1960s, but little success was achieved until the availability of more effective immunosuppressive drugs (cyclosporine) and improved surgical techniques in the early 1980s. The annual number of lung transplant procedures has increased steadily from fewer than 100 per year in the 1980s to more than 2700 transplants reported by 150 worldwide transplant centers in 2007. Lung transplantation is now an accepted therapy for all forms of advanced lung disease.
The most common indications for transplantation are
diseases or conditions that produce extreme disability, are unresponsive to
medical therapy, and are responsible for limited life expectancy. With the
exception of a small number of cases of sarcoidosis and lymphangioleiomyomatosis,
the original lung disease does not usually recur after lung transplantation.
Emphysema accounts for half of all lung transplants performed each year, and
pulmonary fibrosis and cystic fibrosis (CF) each account for 15% of cases
annually. Candidate selection and listing are determined by distinct sets of
disease-specific guidelines. Likewise, a number of standard donor criteria
(e.g., age, size match, tobacco history) must be met in determining donor
selection.
Currently, four types of lung transplantation procedures
are performed. Single-lung transplantation is typically performed through a
posterolateral thoracotomy incision and requires three anastomoses: the
main-stem bronchus, pulmonary artery, and pulmonary veins or left atrium. The
contralateral lung is not removed, so single-lung transplantation is not
performed in patients with bilaterally infected lungs (e.g., patients with CF
or bronchiectasis). Cardiopulmonary bypass is required if there is associated
pulmonary hypertension. More than half of single-lung transplants are performed
for emphysema, and an additional 30% are for fibrotic lung diseases, including
sarcoidosis.
Bilateral lung transplantation was initially performed as
an en bloc procedure with a distal tracheal anastomosis but is currently performed
in a sequential fashion that is functionally equivalent to two single-lung
transplantations completed during a single operation, most commonly through a
transverse sternotomy (“clam-shell”) incision. It requires six anastomoses:
both main-stem bronchi, both pulmonary arteries, and both sets of pulmonary
veins. It is the procedure of choice for patients with bilaterally infected
lungs (e.g., CF or bronchiectasis) and is also performed in certain patients
with emphysema, primary pulmonary hypertension, and other diseases, especially
if there is secondary pulmonary hypertension. Cardiopulmonary bypass is more
likely to be needed in such cases. There has been a trend over the past decade
in favor of bilateral transplants for nearly all indications. This has been
driven by statistically superior late survival; 2007 data demonstrate the
expected half-life of a single lung recipient as 4.6 years; a double lung
recipient can expect a half-life of 6.6 years.
Heart-lung transplantation was initially the most common
type of lung transplant procedure but is now performed infrequently (75 cases
in the United States in 2007). It is an en bloc procedure with right atrial,
aortic, and distal tracheal anastomoses. It is performed in patients with
advanced lung disease and coexistent irreparable cardiac disease usually
associated with fixed pulmonary hypertension, such as those with Eisen-menger
syndrome.
The most recently introduced lung transplant procedure is
living donor lobar transplantation. This procedure involves the removal of a
lower lobe from each of two living donors, with the implantation of one in each
hemithorax of the recipient in a manner similar to bilateral sequential single
lung transplantation.
Postoperative complications of lung transplant include airway
ischemia, dehiscence, and stenosis. Three types of graft rejection may occur:
primary graft dysfunction caused by acute lung injury from ischemia or
reperfusion; acute cellular rejection, manifested by perivascular and
interstitial lymphocytic infiltration; and chronic rejection, seen
histologically as obliterative bronchiolitis. Infection is also a common
complication and is caused not only by the immunosuppression required but also
by the loss of the cough reflex as a result of denervation of the transplanted
lungs.
Bacterial, viral, and fungal pathogens are all seen, with
cytomegalovirus (CMV), human herpesvirus, Aspergil-lus spp., and Candida
spp. common. Prophylaxis against Pneumocystis jiroveci, CMV, and
fungal organisms is used to reduce the incidence of infection.
Immunosuppression is the key to prolonged survival of
transplanted patients but carries the risks of increased infection, especially
with opportunistic organisms; increased malignancy; including posttransplant lymphoproliferative
disorder; and drug toxicity, especially nephrotoxicity. Common induction
regimens use OKT3 or antithymocyte globulin to acutely reduce circulating
lymphocytes. Maintenance therapy usually involves an antiproliferative agent
(calcineurin inhibitor), such as cyclosporine A or tacrolimus (FK506); an
antimetabolite, such as mycoph nolate mofetil or azathioprine; and a
corticosteroid.
