Complications following lung transplantation may impede allograft function and threaten patient survival. The five main complications after lung transplantation are primary graft dysfunction, post-surgical complications, alloimmune responses, infections, and malignancy. Primary graft dysfunction, a transient ischemic/reperfusion injury, appears as a pulmonary edema in almost every patient during the first three days post-surgery. Post-surgical dysfunction could be depicted on computed tomography (CT), such as bronchial anastomosis dehiscence, bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size mismatch. Alloimmune responses represent acute rejection or chronic lung allograft dysfunction (CLAD). CLAD has three different forms (bronchiolitis obliterans syndrome, restrictive allograft syndrome, acute fibrinoid organizing pneumonia) that could be differentiated on CT. Infections are different depending on their time of occurrence. The first post-operative month is mostly associated with bacterial and fungal pathogens. From the second to sixth months, viral pneumonias and fungal and parasitic opportunistic infections are more frequent. Different patterns according to the type of infection exist on CT. Malignancy should be depicted and corresponded principally to post-transplantation lymphoproliferative disease (PTLD). In this review, we describe specific CT signs of these five main lung transplantation complications and their time of occurrence to improve diagnosis, follow-up, medical management, and to correlate these findings with pathology results.
Key Points
• The five main complications are primary graft dysfunction, surgical, alloimmune, infectious, and malignancy complications.
• CT identifies anomalies in the setting of unspecific symptoms of lung transplantation complications.
• Knowledge of the specific CT signs can allow a prompt diagnosis.
• CT signs maximize the yield of bronchoscopy, transbronchial biopsy, and bronchoalveolar lavage.
• Radiopathological correlation helps to understand CT signs after lung transplantation complications.
Hinweise
Xavier Montet and Anne-Lise Hachulla contributed equally
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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
AFOP
Acute fibrinous organizing pneumonia
BOS
Bronchiolitis obliterans syndrome
CLAD
Chronic lung allograft dysfunction
CMV
Cytomegalovirus
CT
Computed tomography
PGD
Primary graft dysfunction
PTLD
Post-transplantation lymphoproliferative disease
RAS
Restrictive allograft syndrome
Introduction
Complications following transplantation may impede allograft function and threaten patient survival. Five principal complications have been described: primary graft dysfunction (PGD), post-surgical complications, alloimmune responses, infections, and malignancy [1, 2].
Improvement in surgical procedures, in particular bronchial anastomosis techniques and the endoscopic management of stenosis or leakage, has contributed to reduce airway complications [3, 4]. Furthermore, systematic infection prophylaxis and a trend for virus serology matching have significantly reduced post-operative morbidity and improved long-term survival with reduced chronic allograft dysfunction [5].
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Nevertheless, these advances are currently unable to completely prevent these complications and clinical follow-up is required with regular lung function assessments, bronchoscopy exams, and computed tomography (CT) scans.
Chest X-ray is performed systematically every year or whenever clinical symptoms occur. Chest CT is a key tool in active follow-up or when chest X-ray is abnormal by allowing early identification and diagnostic clues in the setting of unspecific acute respiratory symptoms, regardless of their origin. Knowledge of the specific CT signs can improve medical management by allowing a prompt diagnosis, by guiding bronchoscopic procedures for bronchoalveolar lavage and transbronchial biopsy. Likewise, the decline of lung function may not always be discriminative between infection or rejection, either acute or chronic, and further investigation by chest CT may help clinicians in establishing a diagnosis before more invasive bronchoscopic procedures.
Complications after lung transplantation vary depending on the delay of their occurrence. Figure 1 summarizes the mean time of occurrence and the greatest incidence of complications depending on the time after the procedure and according to the literature [4, 6, 7].
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In this review, we describe specific CT signs of these five main lung transplantation complications and their time of occurrence to improve diagnosis, follow-up, medical management, guide bronchoscopic procedures, and to correlate these findings with pathology results.
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Primary graft dysfunction
The first lung transplantation complication to occur is primary graft dysfunction. This corresponds to a transient ischemic/reperfusion injury that appears as a pulmonary edema in almost every patient during the first three days post-surgery [8].
PGD is clinically assessed and graded according to the ratio of arterial oxygen pressure to inspired oxygen concentration (PaO2/FiO2) and presence of lung allograft consolidations on the chest radiograph [4]. Ischemia reperfusion injury should be considered after the exclusion of an infectious or cardiogenic etiology. CT signs are pleural or scissural effusions, septal and peribronchovascular thickening, perihilar consolidations, without cardiomegaly, and sparing of the native lung in cases of single lung transplantation (Fig. 2) [7]. It is interesting to note that exudative and hemorrhagic pleural effusions are a normal finding early after thoracic surgery that may persist until the second month.
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Post-surgical dysfunction
Four different post-surgical complications have been described: bronchial anastomosis dehiscence, bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size mismatch, as listed in Table 1.
Table 1
Computed tomography (CT) findings of post-surgical complications
Bronchial anastomosis dehiscence
Bronchial stenosis
Bronchomalacia
Pulmonary artery stenosis
Size mismatch
Time of occurrence
2–4 weeks
2–4 months
2–4 months
0–2 weeks
0–2 weeks
Clinical keys
Dyspnea and recurrent infections
Dyspnea
Recurrent post-obstructive infections
Dyspnea
Recurrent post-obstructive infections
Dyspnea and chest pain
Dyspnea
CT signs
Focal parietal defect
Pneumomediastinum
Pneumothorax
Subcutaneous emphysema
Fixed reduction of bronchial lumen diameter
Dynamic collapse of the bronchus on expiratory acquisition
Reduced caliber
Homolateral hypoperfusion
Dilatation of main PA and right cavities
Allograft atelectasis
Bronchial dehiscence of the anastomosis results mainly from bronchial ischemia because of the absence of reanastomosis of bronchial arteries [9]. It may appear as a focal parietal defect or may be suggested indirectly by pneumomediastinum, pneumothorax, or subcutaneous emphysema 2 weeks after surgery (Fig. 3) [10].
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Afterwards, lesions of bronchial healing from ischemia may also occur, either as bronchial anastomosis stenosis or bronchomalacia [7]. Bronchial stenosis is a fixed reduction of the bronchial lumen diameter and bronchomalacia appears as a dynamic collapse of the bronchus on expiratory acquisition. Both can cause recurrent post-obstructive infections of the involved ventilated regions [4, 5, 7] (Fig. 4).
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Pulmonary artery stenosis could be depicted by a significant difference of the pulmonary arterial diameter between donor and receiver, responsible for ipsilateral pulmonary hypoperfusion depicted on the iodine cartography perfusion map with dual-energy CT (Fig. 5) [11]. Dilatation of the main pulmonary artery and right heart cavities have been described.
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Size mismatch between the donor lung and the recipient thoracic cage can cause areas of atelectasis, or even complete collapse of the allograft in extreme cases (Fig. 6).
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Alloimmune responses
Lung-transplanted patients are at particular risk for alloimmune responses. Acute rejection and chronic lung allograft dysfunction (CLAD) have been described and Table 2 summarizes the alloimmune response findings on CT.
Table 2
Specific CT pattern with alloimmune complications
Alloimmune responses
Acute rejection
BOS
RAS
AFOP
Time of occurrence
1–12 weeks
6–18 months
6–18 months
6–18 months
Clinical keys
Acute dyspnea
Chronic dyspnea, cough
Decrease in FEV1 and FEV1/FVC ratio
Chronic dyspnea
Decrease in FEV1 and TLC
Acute dyspnea
Decrease in FEV1
CT signs
Ground-glass opacities
Interlobular septal thickening
Pleural effusions
Volume loss
“Obstructive phenotype”
Bronchiectasis
Bronchial thickening
Expiratory air-trapping
“Restrictive phenotype”
Bronchiectasis
Peripheral consolidations or ground-glass opacity
Subpleural thickening
Architectural distortion
Upper lobe predominance
Volume loss
Inter-/intralobular septal thickening
Peripheral ground-glass opacity and consolidations
Acute allograft rejection occurs mostly during the first year following transplantation in almost 30% of recipients and may occur as repetitive episodes [1]. Prompt diagnosis and management are necessary because early and repeated exacerbations of acute rejection may lead to CLAD. Many attempts have been made to identify specific signs of acute rejection on CT, but, considered individually, none seem accurate nor have a good predictive value for acute rejection and the degree of severity [12]. Nevertheless, recognition and reporting of CT signs of potential acute allograft rejection are warranted to guide transbronchial biopsy for histopathological analysis.
Typical CT signs are ground-glass opacities, pleural effusions, lung volume loss, and interlobular septal thickening, associated with graduate perivascular and interstitial mononuclear cells infiltration depending on the grade (from minimal perivascular mononuclear infiltrates [grade A1] to severe infiltrates [grade A4]) on histopathology examination (Figs. 7, 8, and 9) [7, 13].
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CLAD
The prevalence of CLAD 5 years after transplantation is 40–50% of patients [1, 14]. CLAD has two distinct phenotypes: obstructive, namely, bronchiolitis obliterans syndrome (BOS) and restrictive, namely, restrictive allograft syndrome (RAS) [15, 16]. CT scans along with lung functions may help in distinguishing between subtypes.
BOS is a constrictive bronchiolitis [13]. CT signs of BOS are bronchiectasis, bronchial thickening, and air-trapping on expiratory acquisition (Figs. 10 and 11) [4, 17‐19].
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Conversely, RAS is a pleuroparenchymal fibroelastosis on histopathology [20], with a more fibrotic pattern on CT and poorer survival. CT signs of RAS are peripheral consolidations or central or peripheral ground-glass opacities, septal or non-septal lines, subpleural thickening, bronchiectasis, architectural distortion, and volume loss with an upper lobe predominance (Fig. 12) [21].
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Some authors have advocated acute fibrinoid organizing pneumonia (AFOP) as a third potential form of chronic allograft dysfunction, with decline of lung functions as for CLAD but with distinct histopathology and imaging findings [22]. Inter- and intralobular septal thickening, extensive ground-glass infiltration, and peripheral consolidations have been described and are consistent with a distinct histopathology entity, either post-infectious or as a distinct form of chronic allograft dysfunction (Fig. 13) [22].
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Infections
Lung-transplanted patients are at particular risk of allograft infections and radiologists should be aware of the epidemiology of pneumonias according to their time of onset. Table 3 summarizes different patterns according to the type of infection.
Table 3
Specific CT pattern with various infections
Infectious diseases
Bacterial germs
Viral germs
Angioinvasive aspergillosis
Time of occurrence
0–4 weeks
4 weeks to 6 months
4–18 months
Clinical keys
Productive cough and high-grade fever/sepsis
Bronchoalveolar lavage
Sputum culture
Productive cough and high-grade fever
General alteration and productive cough
Bronchoalveolar lavage: branching filaments
CT signs
Lobar or patchy consolidations
Air bronchogram
Branching centrilobular nodules
Cavitation
Pleural effusion
Ground-glass nodules
Tree-in-bud nodules
Peribronchovascular thickening
Interlobular septal thickening
Vascular-centered nodules
Ground-glass “halo sign”
Subpleural wedged ground-glass opacity or dense consolidation
The aim of prompt recognition of allograft infection is to reduce immediate morbidity related to symptomatic disease thanks to prompt targeted therapy and to prevent failure of anastomotic healing and long-term chronic allograft dysfunction [5].
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The first post-operative month is mostly associated with bacterial and fungal pathogens [6, 23]. Bacterial infections are the most common. CT signs of bacterial infections include extensive consolidations with air bronchogram, disseminated patchy consolidations, branching centrilobular nodules (Figs. 14 and 15), or cavitation or abscess (Fig. 16).
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CT signs of angioinvasive aspergillosis are isolated or multiple vessel centered nodular consolidations with peripheral ground-glass “halo sign” consistent with hemorrhagic infarcts (Fig. 17) [24].
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From the second to sixth months, long-term immunosuppression of T-cells is responsible for viral pneumonias. CT signs are ground-glass opacities or tree-in-bud nodules (Fig. 18). Fungal and parasitic opportunistic infections can also occur, either from reactivation of latent germs, in particular from cytomegalovirus (CMV), or by community-acquired or nosocomial transmission [6]. CT signs are also ground-glass opacities, tree-in-bud nodules, or an interstitial pattern with peribronchovascular and septal thickening [7].
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After six months, immunosuppression is usually reduced with less opportunistic infections or reactivation of latent pathogens. The most commonly encountered pathogens are community-acquired viral and bacterial, or reactivation of latent Mycobacterium tuberculosis and other mycobacteriae [6, 7]. Individual CT signs are of limited accuracy to distinguish between germs [24]; yet, recognition of some specific patterns of involvement, such as consolidations with air bronchogram, tree-in-bud, or nodules in the context of fever, may favor infection over an alloimmune reaction.
Malignancy
Finally, malignancy remains an important cause of long-term mortality, occurring in almost 25% of patients 5 years after lung transplantation [1, 2]. Malignancy may be confined to the lung allograft or involve distant organs. Post-transplantation lymphoproliferative disease (PTLD) includes a spectrum from lymphoid proliferation to monoclonal lymphoma, affecting 1.8–20% of lung-transplanted patients, with am association with Epstein–Barr virus infection [6, 25]. The manifestation of PTLD includes an isolated nodule or mass of the lung allograft, disseminated micronodules with an interstitial topography, or mediastinal or abdominal lymphadenopathies (Fig. 19) [25].
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Skin malignancies are also predominant, including melanoma, reaching nearly 20% at 10 years. Other cancers could also occur, such as primary epidermoid lung carcinoma (Fig. 20).
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Conclusion
Chest computed tomography (CT) scanning is an important tool in the follow-up of lung transplantation, allowing the diagnosis of pathologies depending on their time of onset in order to improve patient management.
Acknowledgements
All authors declare no support from and no financial relationships with any organization that might have an interest in the submitted work.
Compliance with ethical standards
IRB statement
The local institutional review board approved the study.
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