March 2009, VOLUME 192
NUMBER 3_supplement

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Volume 192, Number 3_supplement

AJR Integrative Imaging: LIFELONG LEARNING FOR RADIOLOGY

Imaging of Lung Transplantation: Review

+ Affiliations:
1CT Unit, Jubilee Wing, Department of Clinical Radiology, Leeds General Infirmary, Leeds LS1 3EX, West Yorkshire, United Kingdom.

2Present address: Department of Diagnostic Radiology, Singapore General Hospital, Outram Rd., Singapore 169608.

3Joint Department of Medical Imaging, Thoracic Division, University Health Network and Mount Sinai Hospital, Toronto General Hospital, Toronto, ON, Canada.

4Department of Clinical Radiology, Hope Hospital, Manchester, United Kingdom.

5Division of Thoracic Surgery and Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.

Citation: American Journal of Roentgenology. 2009;192: S1-S13. 10.2214/AJR.07.7061

ABSTRACT
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OBJECTIVE

Lung transplantation is an established treatment for end-stage pulmonary disease. Complications of lung transplantation include airway stenosis and dehiscence, reimplantation response, acute rejection, infection, posttransplantation lymphoproliferative disorder, and bronchiolitis obliterans syndrome. The incidence of graft rejection and airway anastomosis experienced in the early years of lung transplantation have been significantly reduced by advances in immunosuppression and surgical techniques. Infection is currently the most common cause of mortality during the first 6 months after transplantation, whereas chronic rejection or obliterative bronchiolitis is the most common cause of mortality thereafter. This article reviews the radiologic findings of different surgical techniques as well as the common early and late complications of lung transplantation.

CONCLUSION

Radiology plays a pivotal role in the diagnosis and management of complications of lung transplantation. Advancements in surgical technique and medical therapy influence the spectrum of expected radiologic findings. Familiarity with the radiologic appearances of common surgical techniques and complications of lung transplantation is important.

Keywords: lung transplantation

Introduction
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The first successful isolated single-lung transplantation procedure was performed by the Toronto General Hospital group at the University of Toronto in 1983 [1]. Lung transplantation has since become an established treatment for end-stage pulmonary disease [2]. The registry of the International Society for Heart and Lung Transplantation (ISHLT) recorded an all-time high of 2,169 lung transplantations in 2005 [3]. The main indications for lung transplantation in the 18 months before this writing were chronic obstructive pulmonary disease (COPD, 38%), idiopathic pulmonary fibrosis (IPF, 19%), cystic fibrosis (16%), and α1-antitrypsin deficiency emphysema (8%) (Table 1). The reported survival rates from January 1994 to June 2005 were 87% at 3 months, 78% at 1 year, 62% at 3 years, 50% at 5 years, and 26% at 10 years [3]. Overall, sepsis was the predominant cause of death in the first 6 months after transplantation, whereas chronic graft failure was the main cause of death after 6 months [2].

TABLE 1: Distribution of Diagnoses and Procedures Among Adult Lung Transplant Recipients (January 1995 to June 2006) [ 3 ]

Surgical Techniques
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Single-lung transplantation is usually performed through a posterolateral thoracotomy. On the other hand, bilateral lung transplantation is generally performed through a transverse thoracosternotomy involving bilateral sequential single-lung transplantation [2]. The technique of en bloc double-lung transplantation with tracheal anastomosis is now rarely performed because of the increased rate of anastomotic dehiscence.

Bilateral lung transplantation accounted for 63% of lung transplantation procedures in 2005 [3]. Bilateral lung transplantation is usually performed for chronic pulmonary sepsis such as cystic fibrosis and bronchiectasis (Table 1). It is also the dominant procedure for primary pulmonary hypertension. Bilateral lung transplantation for both COPD and IPF has increased in recent years. This trend may be explained by the higher overall survival rate after bilateral transplantation, by the increased lung function to buffer complications, and by institutional preferences and practices. The lung transplantation program at our institution prefers the use of bilateral lung transplants [2, 3].

Airway anastomotic dehiscence was one of the major obstacles to success in the early years of lung transplantation [4]. The early surgical techniques aimed to reduce the incidence of bronchial dehiscence by improved healing of the anastomoses using intercostal muscle, pericardium, or omentum to wrap the end-to-end bronchial anastomoses [5, 6]. However, the development of significant complications such as diaphragmatic hernias associated with the omental wrap technique [6] encouraged the refinement of surgical techniques and the development of the “telescope technique” (Figs. 1A, 1B, 1C and 1D), which does not require a wrap procedure [7]. With further advances in surgical technique and donor preservation, end-to-end anastomoses without a wrap procedure have been performed with good success [2, 8].

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Fig. 1A —Bronchial anastomosis. Schematic diagram shows end-to-end and “telescope” anastomoses.

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Fig. 1B —Bronchial anastomosis. 41-year-old woman who underwent bilateral lung transplantation in 1980s. CT scan shows area of fat attenuation (asterisk) in thorax, representing omentum used to wrap bronchial end-to-end anastomoses.

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Fig. 1C —Bronchial anastomosis. Axial (C) and coronal (D) CT reformations show normal posttransplantation appearance of telescope anastomoses. Note bronchial overlap; smaller bronchus is “telescoped” into larger bronchus. Internal margin of anastomosis is not sutured and may result in endoluminal flap (arrowhead, D).

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Fig. 1D —Bronchial anastomosis. Axial (C) and coronal (D) CT reformations show normal posttransplantation appearance of telescope anastomoses. Note bronchial overlap; smaller bronchus is “telescoped” into larger bronchus. Internal margin of anastomosis is not sutured and may result in endoluminal flap (arrowhead, D).

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Fig. 2 —Bronchial dehiscence in 28-year-old woman 11 days after bilateral lung transplantation. Patient developed persistent bilateral pneumothoraces (curved arrows) despite bilateral thoracostomy drains (arrowheads). Cause was revealed on CT, which shows focal defect at right bronchial anastomosis and extraluminal air (straight arrow). Note also left lower lobe pneumonia causing consolidation and atelectasis.

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Fig. 3A —Bronchial stricture in 36-year-old man 6 weeks after bilateral lung transplantation. Low-dose (50-mA) axial CT scan (A) and coronal reconstruction (B) show focal tight stenosis at left bronchial anastomosis (arrows).

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Fig. 3B —Bronchial stricture in 36-year-old man 6 weeks after bilateral lung transplantation. Low-dose (50-mA) axial CT scan (A) and coronal reconstruction (B) show focal tight stenosis at left bronchial anastomosis (arrows).

The telescope technique is preferentially used in our institution when there is bronchial size discrepancy. The smaller bronchus is intussuscepted into the larger bronchus, which then helps to maintain an adequate bronchial lumen and act as an anastomotic stent. When bronchial size is equivalent, end-to-end anastomosis is performed [2]. After bronchial anastomosis, the pulmonary artery and vein anastomoses are performed. The bronchial arterial circulation is not reestablished during transplantation, and rearterialization via recipient bronchial arteries requires an estimated 2-4 weeks after surgery [6, 9].

Airway Complications
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The incidence of airway complications has decreased with improved surgical and donor preservation techniques, immunosuppression, and posttransplantation surveillance [4, 8, 10]. Airway complications have been estimated to occur in approximately 5-15% of lung transplants. [4, 6, 9, 10]. The healing of bronchial anastomoses relies on healthy retrograde collateral perfusion from the pulmonary arterial circulation in the initial postoperative period because bronchial arteries are not reanastomosed during transplantation [6, 11]. A suboptimal vascular supply predisposes to ischemia and subsequent ulceration, leading to bronchial dehiscence, stricture formation, and bronchomalacia [6, 12]. Infection and rejection may also play a role.

Airway complications such as bronchial dehiscence and stricture are usually diagnosed by bronchoscopy. However, CT is valuable and is more sensitive than chest radiography in the diagnosis of airway complications [13].

Bronchial dehiscence is the most common airway complication in the early postoperative period, affecting 2-3% of cases [2, 6, 12] and typically occurring 2-4 weeks after transplantation [6, 9, 10]. CT typically shows the presence of extraluminal gas and, occasionally, the focal bronchial wall defect that is pathognomonic of this condition [14] (Fig. 2). Indirect signs of bronchial dehiscence include the presence of a new or persistent air leak, pneumothorax, and pneumomediastinum.

Bronchial stricture formation is seen in approximately 10% of cases; it occurs later in the postoperative period, an average of 3 months after surgery [6, 9, 10]. There is thought to be an increased incidence of stricture formation with the use of the telescope anastomosis technique [8]. CT with multiplanar reconstructions is helpful in depicting strictures and webs and is particularly useful in assessing the extent of bronchial stenoses in order to plan bronchoscopic stent insertion [15] (Figs 3A and 3B).

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Fig. 4A —Pneumothorax after transbronchial biopsy in 45-year-old man. This patient experienced right pleuritic pain after surveillance bronchoscopy and transbronchial biopsy. Immediate chest radiograph shows localized right basal pneumothorax (asterisk).

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Fig. 4B —Pneumothorax after transbronchial biopsy in 45-year-old man. This patient experienced right pleuritic pain after surveillance bronchoscopy and transbronchial biopsy. Subsequent CT scan confirms localized right basal hydropneumothorax associated with right lower lobe atelectasis and bronchiectasis.

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Fig. 5 —Pleural empyema and hematoma in 49-year-old man whose condition deteriorated clinically 8 days after bilateral lung transplantation. CT scan reveals focal fluid collection (single asterisk) in left anterior hemithorax containing gas, suggestive of empyema. Note also large focal collection in right basal hemithorax with higher-attenuation hematoma (double asterisks). Findings were confirmed at thoracotomy.

Vascular Complications
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Vascular anastomotic stenoses, which are more common at the arterial anastomoses, are rare, occurring in fewer than 4% of cases [16]. The risk of pulmonary infarction is greatest in the immediate postoperative period because the transplanted lung does not have an alternative bronchial blood supply. Perfusion scintigraphy may aid in making the diagnosis. The prognosis is usually dismal, but successful outcomes have recently been reported with angioplasty and stent insertion [8].

Mechanical Complications
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Size mismatch between donor lung and recipient thoracic cavity may cause mechanical complications. Most centers will accept size differences of within 25% [17, 18]. If the donor lung is too large for the recipient, distortion of airways and atelectasis may occur, with retained secretions and secondary infections. This may lead to scarring. The oversized lung graft may be intraoperatively reduced to match the capacity of the recipient. If the donor lung is too small for the recipient, graft hyperexpansion may lead to hemodynamic compromise, limited exercise tolerance, or frank pulmonary hypertension, all because of an inadequate vascular bed [17]. In patients with emphysema who undergo single-lung transplantation, the small graft may be compressed by the emphysematous native lung, resulting in restrictive pulmonary function [18]. Lung volume reduction surgery may be performed during the transplantation procedure.

Pulmonary torsion is a rare but serious complication that may occur in the immediate postoperative period. Imaging features of pulmonary torsion are related to the torquing of the hilar structures, the airway, and the vasculature, and include a collapsed lobe (due to airway compromise) or an expansile consolidated lobe (due to hemorrhagic infarction) in an atypical location [19]. Other features that may be present are bronchial cutoff, inappropriate hilar displacement associated with an atelectatic lobe, abnormal position of pulmonary vasculature and bronchi, rapid opacification of a lobe or lung, and change in position of an opacified lobe on sequential radiographs. Once pulmonary torsion is suspected, immediate surgery is indicated to avoid death from lobar infarction.

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Fig. 6 —Diagram shows typical time course for onset of pulmonary parenchymal complications after lung transplantation. PTLD = posttransplantation lymphoproliferative disorder.

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Fig. 7A —Reimplantation response in 33-year-old woman 2 days after bilateral lung transplantation. Chest radiograph shows typical features of reimplantation response: bilateral perihilar and basal consolidation.

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Fig. 7B —Reimplantation response in 33-year-old woman 2 days after bilateral lung transplantation. CT scan shows bilateral patchy ground-glass opacities and septal thickening in addition to consolidation.

Pleural Complications
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Pleural complications are seen in 22-34% of patients after transplantation [20, 21]. Bilateral-lung and heart-lung transplantations frequently result in a single communicating pleural space. Therefore, fluid and gas collections are often bilateral [8].

Pneumothorax is the most common pleural complication; it usually resolves with the insertion of thoracostomy drains [8, 21]. New, persistent, or enlarging pneumothoraces should prompt further investigations to elucidate the cause of the air leak (Fig. 2). Pneumothorax may also occur after transbronchial biopsy (Figs. 4A and 4B).

Pleural effusions develop in almost all patients because of increased capillary permeability and impaired lymphatic clearance of the transplanted lung [12, 20]. They are usually self-limiting and resolve within 2 weeks. Persistent or delayed effusions suggest complicated effusions such as empyema, organized hematoma, rejection, and posttransplantation lymphoproliferative disorder (PTLD). Empyema occurs in approximately 4% of patients and may affect both hemithoraces, with potential disastrous consequences [8, 20] because it is the only pleural complication associated with an increased mortality rate [21]. Therefore, empyema should be excluded in the presence of a new or enlarging pleural effusion (Fig. 5).

Pulmonary Parenchymal Complications
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Many pulmonary parenchymal complications after lung transplantation have nonspecific radiologic findings. Correlation with the time interval from transplantation is helpful to narrow the differential diagnoses (Fig. 6). Clinical correlation and bronchoscopy with transbronchial biopsy are also often required.

Reimplantation Response
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Reimplantation response, also known as reperfusion edema, is a form of noncardiogenic pulmonary edema that occurs in more than 95% of patients [22] (Figs. 7A and 7B). It frequently begins by postoperative day 1, is always present by day 3, peaks by day 4 or 5, and resolves by day 10 [8, 11]. Persistence beyond the first week suggests infection or acute rejection. Reimplantation response is usually diagnosed after exclusion of left ventricular failure, fluid overload, transplant rejection, and infection [22, 23].

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Fig. 8A —Acute rejection diagnosed on transbronchial biopsy in 51-year-old woman 7 days after bilateral lung transplantation. Portable chest radiograph shows nonspecific pulmonary opacities in perihilar, mid, and lower lung bilaterally.

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Fig. 8B —Acute rejection diagnosed on transbronchial biopsy in 51-year-old woman 7 days after bilateral lung transplantation. CT images show bilateral patchy ground-glass opacities, consolidation, and interlobular septal thickening (arrows, B).

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Fig. 8C —Acute rejection diagnosed on transbronchial biopsy in 51-year-old woman 7 days after bilateral lung transplantation. CT images show bilateral patchy ground-glass opacities, consolidation, and interlobular septal thickening (arrows, B).

Chest radiography and CT typically show bilateral perihilar and basal air-space consolidation [22]. The pathogenesis is probably multifactorial: increased vascular permeability due to ischemia and subsequent reperfusion, lymphatic interruption, lung denervation, decreased surfactant production, and surgical trauma [12].

Acute Rejection
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Acute rejection usually occurs within the first 3 weeks, typically between postoperative days 5 and 10 [8] (Figs. 8A, 8B and 8C). Most patients experience two or three significant rejection episodes in the first 3 months after transplantation [12]. Repeated episodes of acute rejection are associated with an increased risk of chronic rejection (i.e., bronchiolitis obliterans syndrome) [24].

The radiographic features may be similar to those of reimplantation response and infection. The presence of new, persisting, or progressive perihilar and basal opacities or pleural effusions with septal lines 5-10 days after transplantation without other signs of left ventricular failure is suggestive of acute rejection [8, 25]. CT findings include ground-glass opacities, interlobular septal thickening, nodules, consolidation, and volume loss. Ground-glass opacities are often patchy and localized in mild rejection but wide-spread in severe rejection [26]. However, CT has limited accuracy in the diagnosis or grading of severity of acute rejection [24].

Patients may be asymptomatic or may present with dyspnea, fever, leukocytosis, and decreased exercise tolerance. Investigations reveal a decrease in arterial oxygenation and forced expiratory volume in 1 second (FEV1). The most useful feature is the dramatic clinical and radiographic response to corticosteroids and increased immunosuppression [8, 23]. Transbronchial biopsy is often performed to confirm the diagnosis and to exclude infection [8].

Infection
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Infection is the most common complication after transplantation and is a major cause of morbidity and mortality [2]. Patients have increased susceptibility to infection because of immunosuppression, lung denervation and loss of the cough reflex, impaired mucociliary function, and lymphatic drainage [8, 27].

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Fig. 9A —Infections with Aspergillus organisms in two patients. 26-year-old man developed aspergillosis 1 month after bilateral lung transplantation. CT scan shows multiple nodules (curved arrows), some with surrounding ground-glass halo sign (arrowheads) and cavitation (straight arrow).

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Fig. 9B —Infections with Aspergillus organisms in two patients. CT scan in 37-year-old man 3 weeks after bilateral lung transplantation shows patchy ground-glass opacities in left lower lobe. Culture of bronchial washings was positive for Aspergillus organisms.

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Fig. 10A —Cytomegalovirus pneumonia in seropositive 44-year-old man after bilateral lung transplantation. Chest radiograph shows nonspecific bilateral basal patchy and hazy opacities.

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Fig. 10B —Cytomegalovirus pneumonia in seropositive 44-year-old man after bilateral lung transplantation. CT scan shows bilateral patchy ground-glass attenuation and micronodules.

Bacterial infections predominate in the first 4 weeks after transplantation; viral infections are generally not seen until the following month. Fungal infections can occur at any period after transplantation. Pneumocystis pneumonia is now uncommon because of the routine use of trimethoprim-sulfamethoxazole prophylaxis [12].

Bacterial Infection

Bacterial infections account for at least 50% of all infections [11]. The incidence is highest in the first month, but remains a significant complication throughout the patient's life [8, 27]. Death is unusual in the immediate postoperative period because of the wide use of broad-spectrum antibiotics.

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Fig. 11A —Posttransplantation lymphoproliferative disorder (PTLD) in 26-year-old man 4 months after bilateral lung transplantation. Multiple lung nodules were detected incidentally on surveillance chest radiograph.

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Fig. 11B —Posttransplantation lymphoproliferative disorder (PTLD) in 26-year-old man 4 months after bilateral lung transplantation. CT scan shows multiple nodules with surrounding halo of ground glass (arrows). Percutaneous CT-guided biopsy confirmed diagnosis of PTLD.

The most common causative organisms are gram-negative bacilli such as Klebsiella organisms, Pseudomonas aeruginosa, and Enterobacter cloacae. Gram-positive organisms such as Staphylococcus aureus are also observed [8, 11]. In patients with cystic fibrosis, the presence of Burkholderia cepacia is associated with severe postoperative infections and reduced survival rates [2].

Radiologic features are similar to those of nontransplant patients: lobar or multifocal consolidation, ground glass opacity, cavitation, and lung nodules [8, 27].

Fungal Infection

Fungal infections, most commonly Candida and Aspergillus organisms, usually occur between 10 and 60 days after transplantation [27]. They are less common but are associated with a higher mortality rate than viral infections [8]. Candida species frequently colonize the airways, but invasive pulmonary infection is uncommon.

Aspergillosis is more prevalent in lung transplantation patients than in other immunocompromised patients. Locally invasive or disseminated infection with Aspergillus organisms accounts for 2-33% of infections after lung transplantation and 4-7% of all lung transplantation deaths [27]. Aspergillus organisms can cause indolent pneumonia or fulminant angio-invasive infection with systemic dissemination (Figs. 9A and 9B). CT commonly reveals a combination of ill-defined nodules, cavitary opacities, consolidation, and ground-glass opacity [27]. Symptoms are nonspecific and include fever, cough, pleuritic chest pain, and hemoptysis [8].

Aspergillus infections in the airway are seen in 5% of patients, mostly in the first 6 months. They are usually asymptomatic and are detected on surveillance bronchoscopy. Such an infection may cause ulcerative tracheobronchitis that is usually radiologically occult and can lead to bronchial dehiscence, stenosis, or bronchomalacia [8].

Viral Infection

Cytomegalovirus (CMV) is the second most common cause of pneumonia in lung transplantation patients and is the most common opportunistic infection [8] (Figs. 10A and 10B). CMV pneumonia most commonly occurs between 1 and 12 months, with a peak incidence at 1-4 months [27].

Chest radiographs may be normal or may show diffuse parenchymal haziness or reticulonodular interstitial opacities. CT findings include areas of ground-glass attenuation, micronodules, consolidation, reticulation, and small pleural effusions [8, 27].

Patients may be asymptomatic or develop fulminant pneumonia. Clinical manifestations include dyspnea, fever, cough, and malaise [12]. CMV pneumonia is associated with an increased risk of superadded bacterial and fungal infections as well as the development of bronchiolitis obliterans syndrome. Diagnosis can be made by bronchoalveolar lavage and transbronchial biopsy.

Primary infection occurs in CMV-seronegative recipients who receive a graft from a seropositive donor. Infection develops in more than 90% and is serious in 50-60% of cases [27]. Thus, CMV matching between donor and recipient is performed whenever possible. Secondary infection develops from reactivation of a latent virus after immunosuppression or from infection with a different CMV strain and is usually less serious than the primary infection [8].

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Fig. 12A —Obliterative bronchiolitis in two patients. Chest radiograph (A) in 35-year-old woman 9 months after bilateral lung transplantation shows decreased vascular markings and increased lung volumes. CT scan (B) shows minor bronchial dilatation and mosaic attenuation. Transbronchial biopsy revealed obliterative bronchiolitis.

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Fig. 12B —Obliterative bronchiolitis in two patients. Chest radiograph (A) in 35-year-old woman 9 months after bilateral lung transplantation shows decreased vascular markings and increased lung volumes. CT scan (B) shows minor bronchial dilatation and mosaic attenuation. Transbronchial biopsy revealed obliterative bronchiolitis.

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Fig. 12C —Obliterative bronchiolitis in two patients. Inspiratory (C, 50 mAs) and expiratory (D, 20 mAs) CT scans show bronchial dilatation and air trapping in right lower lobe in 45-year-old man with known obliterative bronchiolitis.

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Fig. 12D —Obliterative bronchiolitis in two patients. Inspiratory (C, 50 mAs) and expiratory (D, 20 mAs) CT scans show bronchial dilatation and air trapping in right lower lobe in 45-year-old man with known obliterative bronchiolitis.

Other viral agents include herpes simplex virus, adenovirus, and respiratory syncytial virus.

Posttransplantation Lymphoproliferative Disorder
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PTLD is a spectrum of diseases that vary from a histologically benign polyclonal lymphoid proliferation to aggressive high-grade lymphoma [28]. It may manifest from 1 month to several years after transplantation but tends to occur within the first year, peaking at 3-4 months [23] (Figs. 11A and 11B). The incidence is approximately 5% (range, 1.8-20%), and it is more common with lung transplantation than with other solid organ transplantations [11, 28]. The variability in the incidence probably reflects differences in immunosuppression, ages of the study population, rates of Ebstein-Barr viral (EBV) infections, and CMV prophylaxis.

Radiographically, PTLD usually manifests as solitary or multiple pulmonary nodules or masses [28]. Extrapulmonary involvement—hilar or mediastinal adenopathy, thymic enlargement, pleural effusions, and pericardial masses—is less common [11]. Clinical manifestations include low-grade fever, lethargy, and weight loss. Patients may also be asymptomatic.

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Fig. 13A —Recurrent disease in three patients. Recurrent disease in 52-year-old woman 2 years after bilateral lung transplantation for sarcoidosis. CT scan shows nonspecific opacities in right lower lobe; transbronchial biopsy revealed noncaseating granulomas.

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Fig. 13B —Recurrent disease in three patients. 47-year-old woman with lymphangioleiomyomatosis (LAM) underwent bilateral lung transplantation. She developed chylothorax (arrow indicates fat-fluid level) and retroperitoneal lymphadenopathy, which proved at histology to be recurrent LAM.

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Fig. 13C —Recurrent disease in three patients. 58-year-old woman underwent bilateral lung transplantation 18 months earlier for multifocal bronchioloalveolar carcinoma. CT scan shows multiple nodules. Transbronchial biopsy confirmed recurrent disease.

PTLD is thought to be secondary to B-lymphocyte proliferation in response to EBV infection [11]. It is more commonly seen in EBV-seronegative recipients who receive an EBV-seropositive donor lung. Aggressive immunosuppression regimens are also thought to be a cause [28]. Most cases respond to antiviral agents (e.g., acyclovir) and a reduction or cessation of immunosuppressive therapy.

Obliterative Bronchiolitis
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Obliterative bronchiolitis is thought to be a manifestation of chronic rejection, affecting up to 50% of patients (Figs. 12A, 12B, 12C and 12D). It is a major source of morbidity and mortality and is now the greatest limitation to long-term survival after lung transplantation [2, 8, 11]. It usually develops within 6-18 months after transplantation but may occur as early as the second month. Significant association with previous multiple episodes of acute rejection and CMV pneumonia has been reported. Other potential risk factors include other lung infections, gastroesophageal reflux, and human leukocyte antigen mismatching [29].

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Fig. 14A —56-year-old man who developed bilateral upper lobe fibrosis 2 years after bilateral lung transplantation. Chest radiograph shows bilateral upper lobe reticular opacities and volume loss.

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Fig. 14B —56-year-old man who developed bilateral upper lobe fibrosis 2 years after bilateral lung transplantation. CT scan shows coarse reticulation, architectural distortion, traction bronchiectasis (arrowhead), and honeycombing (arrow).

Obliterative bronchiolitis is a histologic diagnosis; changes affect the small airways in a patchy distribution. Transbronchial biopsy may not be diagnostic, particularly in the early stages [30]. Therefore, the disorder is frequently diagnosed clinically, using the term “bronchiolitis obliterans syndrome,” on the basis of an otherwise unexplained decline in lung function [29]. Patients generally present with a cough and worsening dyspnea [11].

The chest radiograph may be normal or may show attenuated pulmonary vessels, bronchial cuffing, subsegmental atelectasis, and irregular linear opacities [13, 31]. Lung volumes can be normal or mildly increased. CT typically shows bronchial dilatation, bronchial wall thickening, and mosaic attenuation that are most marked in the lower lobes [31]. Air trapping is frequently depicted on expiratory CT in patients with obliterative bronchiolitis and can also be seen on inspiratory CT in areas of lower attenuation with attenuated pulmonary vessels. However, the presence of air trapping is of limited sensitivity for the early diagnosis of obliterative bronchiolitis [32].

Recurrent Disease
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Recurrent disease in the transplanted lung is uncommon, affecting approximately 1% of recipients. Sarcoidosis, lymphangioleiomyomatosis, bronchioloalveolar carcinoma, and Langerhans cell histiocytosis have been reported to recur in the transplanted lung [8, 33]. The radiologic features of recurrent disease in the donor lung are similar to those of the original disease, but they may mimic other posttransplantation complications such as infection, rejection, and PTLD.

Sarcoidosis is the most commonly reported disease to recur, with a frequency of 35% [34] (Fig. 13A). Recurrence of sarcoidosis has been reported as early as 2 weeks and as late as 2 years after transplantation. It is an incidental finding at transbronchial lung biopsy in most cases. Transbronchial biopsy shows multiple noncaseating giant cell epithelioid granulomas. Because granulomas can also be seen with mycobacterial or fungal infection, it is important to exclude these diagnoses. A negative transbronchial lung biopsy does not exclude recurrent sarcoidosis because of the patchy nature of the disease.

Patients who have undergone lung transplantation for lymphangioleiomyomatosis have increased morbidity and mortality due to complications related to their underlying disease—for example, native lung pneumothorax, chylothorax, chylous ascites, hemorrhagic renal angiomyolipomas, and recurrence of disease—from 1 to 5 years after transplantation [34] (Fig. 13B).

Recurrence of bronchioloalveolar carcinoma has occurred in approximately 50% of patients who survive the transplantation [33] (Fig.13C). Recurrence is usually limited to a transplant graft and is slow-growing despite immunosuppression. Lung transplantation for the treatment of multifocal bronchioloalveolar carcinoma is not widely established, and represents only approximately 0.1% of transplantations recorded by the ISHLT [3] (Table 1). Lung transplantation is unlikely to be curative but can achieve a 5-year survival rate of 39%, which is similar to that for other end-stage pulmonary diseases [33].

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Fig. 15A —After transbronchial lung biopsy, nodules are confined to one lung because surveillance transbronchial biopsies are only performed from one lung, usually the right, at our institution. 42-year-old man who underwent surveillance bronchoscopy and transbronchial biopsy 7 days before surveillance CT, which showed cavitary nodules (arrowheads) surrounded by ground-glass attenuation.

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Fig. 15B —After transbronchial lung biopsy, nodules are confined to one lung because surveillance transbronchial biopsies are only performed from one lung, usually the right, at our institution. 39-year-old man who underwent surveillance transbronchial biopsy 3 days before surveillance CT, which showed solid nodules (arrows) surrounded by ground-glass attenuation.

Upper Lobe Fibrosis
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Upper lobe fibrosis is uncommon, reported to occur 18-72 months (average, 42 months) after lung transplantation [35] (Figs. 14A and 14B). The exact pathogenesis is unknown but is hypothesized to be a rare manifestation of chronic rejection. Pathologic assessment may show nonspecific inflammation and fibrosis.

High-resolution CT findings include interlobular septal thickening, gradual development of coarse reticular opacities, and mild peripheral ground-glass opacities. The progression of established fibrosis may occur with traction bronchiectasis, honeycombing, architectural distortion, and volume loss. The upper lobes are initially involved, with the subsequent development of smaller volumes of fibrosis in the superior segments of the lower lobes [35]. The basal segments are minimally involved.

Patients develop progressive dyspnea. Pulmonary function tests may show a mixed obstructive and restrictive pattern.

Complications After Transbronchial Biopsy
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Solid and cavitary nodules (2-15 mm) with surrounding ground-glass attenuation may be identified on CT up to 1 month after transbronchial biopsy [36] (Figs. 15A and 15B). The ground-glass attenuation represents hemorrhage secondary to biopsy. The nodules may not be immediately evident on chest radiographs. The temporal relationship to the biopsy and the location at known biopsy sites should prevent confusion with infection or rejection.

Summary
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Radiology plays a pivotal role in the diagnosis and management of complications of lung transplantation. Radiologists should be familiar with the radiologic appearances of common surgical techniques as well as those of complications of lung transplantation. Because the radiologic pattern of disease may be nonspecific, it is critical to know the time course from lung transplantation and relevant postoperative history in order to generate a clinically useful and relevant radiologic opinion.

Address correspondence to Y. L. Ng ().

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