is an Associate Professor of Radiology, Department of Radiology,
Medical University of South Carolina, Charleston, SC.
is a Professor of Radiology, Department of Radiology, Duke
University Medical Center, Durham, NC.
In 1983, lung transplantation became a clinical reality and the
number of procedures performed is steadily increasing.
Approximately 1400 lung transplants are performed worldwide each
and there are now >17,000 patients in the International Society
for Heart and Lung Transplantation (ISHLT) registry.
Although the procedure itself remains limited to various regional
centers, as more and more patients with lung transplants return to
their home communities, it will be important for radiologists to
appropriately image as well as recognize complications that can
result from the procedure. The purpose of this article is to
discuss the important imaging considerations related to lung
transplantation, particularly those that are expected to develop
outside the transplant center.
Overview of lung transplantation
For many patients with end-stage lung disease, lung transplant
is the only option available, and it offers the chance for their
quality of life to be significantly improved. In the adult, the
vast majority of lung transplants are performed for 4 conditions:
chronic obstructive pulmonary disease (COPD) (39%), idiopathic
pulmonary fibrosis (17%), cystic fibrosis (16%), and
alpha-1-antitrypsin deficiency (9%).
Whenever possible, bilateral lung transplants are preferred;
however, in cases of pulmonary fibrosis and selected cases of
emphysema, single-lung transplants are acceptable and help to
distribute needed organs to a larger population of critically ill
patients. Because of the risk of infection and cross-contamination,
unilateral lung transplants are contraindicated in patients with
cystic fibrosis and bronchiectasis. Overall, an equal number of
single- and double-lung transplants have been performed annually
The benefit of lung transplantation comes in the form of both
survival and quality of life.
However, the benefit is not realized until 3 to 6 months following
transplant and comes with up-front risk. Even in experienced
transplant programs, operative mortality rates may be as high as 8%
and 3month survival is approximately 84%.
From 1992 to 2003, overall survival at 1, 3, 5, and 10 years was
74%, 58%, 47%, and 24%, respectively, with the average life
expectancy following transplant just more than 3 years. In general,
patients with COPD, emphysema, and cystic fibrosis fare better than
those who received transplants for other conditions.
Preoperative imaging considerations
The preoperative imaging evaluation is designed to assess the
transplant candidate for suitability and to select the most
appropriate hemithorax in those considered for single-lung
transplantation. To that end, these patients will undergo chest
radiography, computed tomography (CT), and quantitative perfusion
scintigraphy, at a minimum. Important considerations include the
presence or absence of suspicious lung nodules, the presence or
absence of pleural disease, or the presence of any other anatomic
features that may impact surgical technique and differential
The presence of mycetomas, while not an absolute contraindication,
has been associated with a much higher mortality rate.
Preferably, the lung with the worse function will be transplanted.
In 11% of cases, CT findings will change the lung selected for
transplantation when compared with chest radiography.
As lung cancer is an absolute contraindication to transplant,
suspicious lesions on CT should be evaluated thoroughly prior to
transplant. The rate of cancer detection is similar to that of
screening a high-risk population (1% to 2%).
In young patients with cystic fibrosis who are being considered for
bilateral lung transplantation, CT has limited utility and has not
been shown to change the surgical approach and, thus, may be
omitted in this limited circumstance.
Inherent difficulties in the management of potential organ
donors following brain death put a strain on the number of
available organs. Fortunately, a more aggressive approach to donor
selection and extended acceptance criteria has been successful at
increasing available donor organs without adversely affecting
In an optimal situation, donors should have a normal chest
radiograph and no evidence of chest trauma or aspiration. However,
the presence of improving air-space opacities, contusion,
pneumothorax, or pleural effusion does not appear to impact the
postoperative course. Worsening or persistent air-space opacities
in a potential donor remains a contraindication to using the lungs
Imaging in the immediate postoperative period
In the postoperative period, there are 3 major complications:
Reperfusion edema, acute rejection, and infection. Reperfusion
edema (Figure 1) is the most frequent immediate postoperative
complication that occurs within several hours up to 48 hours
following the procedure and is characterized radiographically by
mixed interstitial and air-space opacities in the transplanted
lung(s) and by small pleural effusions.
Risk factors include poor organ preservation, prolonged ischemic
time, unsuspected donor pathology such as contusion and aspiration,
interrupted lymphatic supply, and cytokine-mediated injury.
Treatment consists of diuresis and mechanical support. With
appropriate therapy, the condition generally improves over the next
24 to 48 hours and resolves over 7 to 10 days, rarely contributing
to morbidity and mortality by itself.
Acute rejection has a radiographic appearance similar to
reperfusion injury (Figure 2)-that is, mixed interstitial and
air-space opacities with associated pleural effusions.
Therefore, the timing of edema is important, as acute rejection
usually does not develop until 7 to 10 days following the procedure
at the earliest. Reperfusion edema and acute rejection are best
distinguished by the temporal relationship to the transplant
procedure. CT is of limited utility in the diagnosis. Ground-glass
opacities, septal lines, and pleural effusions are often present
Most patients will have at least 1 episode of acute rejection in
the first year following transplant.
It is important to recognize that infections may occur at any
time during the postoperative period and may coexist with edema and
acute rejection. Infection has a major impact on survival and is a
primary cause of postoperative mortality in up to 50% of cases.
The radiographic manifestations are varied and reflect the nature
of the organism and the host response. Bacterial organisms (usually
, and other gram-negative organisms) are the most frequent cause of
infection in the immediate postoperative period.
Because of impaired fluid clearance through the pleura,
effusions (frequently transudative effusions) occur in almost every
While not all effusions require drainage, small-bore catheter
drainage is usually successful.
Occasionally, effusions may require protracted drainage to effect a
Imaging of complications after discharge
Although bacterial infections predominate in the first month
following lung transplant, viral infections, particularly
cytomegalovirus (CMV), become more frequent in the second and third
months and continue thereafter. While the exact incidence of CMV
pneumonia after lung transplant is unclear, it is estimated to
occur in up to 86% (range 35% to 86%) of transplant recipients,
even with appropriate prophylaxis. Mortality for CMV pneumonia
ranges from 2% to 12%.
Also, CMV infection remains an important cause of bronchiolitis
obliterans syndrome (BOS), described later.
The radiographic manifestations (Figure 3) have been described
in small series and include heterogeneous air-space opacities,
ground-glass opacities, nodules, septal lines, and pleural effusion
in relatively similar frequency.
In unilateral lung transplant recipients, infection usually occurs
in the transplanted lung. Other viral organisms (including
influenza, parainfluenza, respiratory syncytial virus, and
adenovirus) have also been described. Radiographs are essentially
normal in half of the cases. In cases with abnormal findings,
nonspecific heterogeneous opacities are the rule.
Fungal infections (mainly with
species) may also occur at any time.
species cause infection in 6% of cases
and appear to have a higher incidence in patients with cystic
fibrosis and in patients who had a single-lung transplant for COPD.
Unfortunately, it can be quite difficult to separate colonization
from true infection. In the majority of cases, the infection is
either a tracheobronchitis or an anastomotic infection, whereas
invasive pulmonary infections and disseminated disease are less
infection in the airways include both stenosis and anastomotic
dehiscence. Overall mortality is approximately 50%.
Radiographic findings are primarily based on the site of
disease. Chest radiographs are generally normal in
tracheobronchitis. CT, including virtual bronchoscopy, may reveal
surface mucosal irregularities (Figure 4) and be useful to document
stenosis and dehiscence in certain circumstances.
However, since the diagnosis must be established by bronchoscopy,
there is no primary role for CT in this regard. Nodules and focal
consolidation are the primary manifestations of invasive disease
both with chest radiographs and CT,
and findings are similar to those of invasive
infection in other settings.
Acute rejection, described previously, may occur at any time,
although the ma-jority of episodes occur within the first year
(Figure 5). Chronic rejection, also termed
bronchiolitis obliterans syndrome
(BOS), is quite common and probably develops in all transplant
patients given sufficient time. Risk factors include frequent or
severe bouts of acute rejection, infection, and gastroesophageal
The diagnosis is established by pulmonary function testing and
graded by criteria developed by the ISHLT (Table 1).
Bronchiolitis obliterans syndrome remains the most significant
barrier to long-term survival, and, unfortunately, it is difficult
to establish the diagnosis early.
Initially, it was hoped that high-resolution CT (HRCT) would
provide early clues to BOS and predict those who are at risk for
development of BOS, thus allowing for earlier treatment. Chief
among possible clues was the presence of air trapping on expiratory
CT; various strategies have been developed to document air trapping
(Figure 6). Early reports put the sensitivity of air trapping on
expiratory HRCT between 75% to 90%.
With the revision of the ISHLT grading system, expiratory CT has
been found to be less sensitive than had been previously thought,
and this undoubtedly reflects the greater reliance on more subtle
physiologic changes for the diagnosis. When air trapping is
present, the specificity of CT has been found to be quite good in
Other CT findings of BOS include mosaic attenuation, cylindrical
bronchiectasis (Figure 7), and bronchial wall thickening. These
features have been shown to be weak correlates of disease severity,
With refinements in surgical technique, bronchial complications
are less frequent. Complete dehiscence is quite rare and requires
surgical intervention. More commonly (but still rarely) an
incomplete dehiscence will occur. Chest radiographs may reveal an
expanding pneumothorax or pneumomediastinum but most often do not
reveal acute abnormalities.
At CT, focal defects of the bronchial wall and perianastomotic air
collections may be seen.
The majority of incomplete dehiscence can be managed
conservatively, and some may heal spontaneously.
An important mimicker of dehiscence is the telescoping bronchus.
This technique results in an end-to-end anastomosis of the
posterior membranous portion of the bronchus and invagination of
the cartilaginous portion of the smaller bronchus into the larger
The telescoping segment, therefore, arises from either the donor or
the recipient. On axial CT images, the telescoped segment may have
the appearance of a bronchial wall defect or an apparent
extraluminal gas collection.
Thin sections with oblique coronal reformatted images are valuable
in separating the telescoping bronchus from dehiscence.
Stenosis at the anastomotic site is a more common occurrence
(Figure 8). Both CT and virtual bronchoscopy are accurate for
; however, as fiberoptic bronchoscopy is required for definitive
diagnosis and management, the utility of CT is limited. Management
strategies include debridement of granulation tissue or stent
Posttransplant lymphoproliferative disorder
Posttransplant lymphoproliferative disorder (PTLD) is an
uncommon complication in transplant recipients and occurs in <6%
Posttransplant lymphoproliferative disorder covers a wide spectrum
of lymphoid proliferation that ranges from hyperplastic colonies of
polyclonal B-cells to aggressive monoclonal high-grade lymphoma. A
slight majority occurs in the first year after transplant.
Intrathoracic disease is most common in the first year, whereas
late development of PTLD is associated with extra-thoracic sites of
disease (Figure 9).
The most important risk factors include immunosuppression with
cyclosporine and Epstein-Barr virus infection. The most common
findings, both at chest radiography and CT, are multiple
well-circumscribed pulmonary nodules with or without a ground-glass
Other reported radiographic findings include hilar and mediastinal
adenopathy, parenchymal consolidation, and pleural masses. Disease
outside the thorax most frequently occurs in the gastrointestinal
tract but may also be seen in the skin, oropharynx, and solid
Lung cancer develops in the native lung of single-transplant
recipients in approximately 1% of cases, with slightly higher rates
overall for those with emphysema and pulmonary fibrosis (Figure
In a multicenter series, 9 of 24 lung cancers (38%) were stage I.
Recurrence of the primary disease has been described with many
conditions, including sarcoidosis, lymphangio-leiomyomatosis,
Langerhans cell histiocytosis, talc granulomatosis, diffuse
panbronchiolitis, and alveolar proteinosis. Although the overall
incidence of recurrence is approximately 1% of all transplant
recipients, it is a relatively common phenomenon in patients with
sarcoidosis (35% recurrence rate).
Disease recurrence often occurs without overt radiographic findings
or is found incidentally at transbronchial biopsy. When
radiographic findings are present, they generally follow the
typical features of the underlying disease. In sarcoidosis, rather
than adenopathy, fine interstitial opacities and miliary nodules
are the most common manifestations of recurrent disease (Figure
Complications in the native lung should not be overlooked in
single-lung transplant recipients. In up to 50% of cases of
emphysema, progressive hyperinflation develops (Figure 12). This,
in turn, can have adverse effects on the transplanted lung through
compression and an increase in pulmonary vascular resistance.
In one transplant center, native lung complications (aside from
hyperinflation) occurred in 15%, most often infectious, and caused
serious morbidity and mortality in 70% of patients.
Lung transplantation is increasingly utilized in the management
of end-stage pulmonary diseases. Practicing radiologists who are
not affiliated with transplant centers need to be aware of the
various conditions and complications related to lung
transplantation so that appropriate management can be implemented