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(Radiology. 2001;218:233-241.)
© RSNA, 2001

Thoracic Imaging

Complications (Excluding Hyperinflation) Involving the Native Lung after Single-Lung Transplantation: Incidence, Radiologic Features, and Clinical Importance1

H. Page McAdams, MD, Jeremy J. Erasmus, MD and Scott M. Palmer, MD

1 From the Departments of Radiology (H.P.M., J.J.E.) and Medicine, Division of Pulmonary and Critical Care Medicine (S.M.P.), Duke University Medical Center, Box 3808, Durham, NC 27710. Received February 22, 2000; revision requested April 7; revision received May 17; accepted June 1. Address correspondence to H.P.M. (e-mail: mcada003@mc.duke.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To determine the incidence, importance, and radiologic features of native lung complications after single-lung transplantation.

MATERIALS AND METHODS: Seventeen (15%) of 111 single-lung transplant recipients developed native lung complications (excluding hyperinflation) 0–58 months (mean, 17 months) after transplantation. Complaints at presentation, culture or histopathologic results, diagnostic or therapeutic procedures, and outcome were recorded. Chest radiographs (n = 17) and computed tomographic (CT) scans (n = 8) obtained at time of diagnosis were reviewed. Serial radiographs were assessed for disease progression or improvement.

RESULTS: The most common complications were infection (n = 10), caused by bacteria (n = 4), fungi (n = 4), or mycobacteria (n = 2), typically manifested as lobar or segmental opacities on chest radiographs or CT scans. Lung cancer manifested as a solitary well-circumscribed nodule (n = 1), multiple nodules (n = 1), or a hilar mass (n = 1). Five (29%) of 17 patients died of native lung complications. Seven patients underwent mediastinoscopy (n = 3), lobectomy (n = 2), thoracoscopic wedge resection (n = 2), tube thoracostomy (n = 2), or pneumonectomy (n = 1) for diagnosis or treatment.

CONCLUSION: Native lung complications occurred in 17 (15%) single-lung transplant recipients, were most commonly due to infection or lung cancer, and caused serious morbidity or mortality in 12 (71%) of 17 patients affected.

Index terms: Lung, abnormalities, 60.20, 60.2059, 60.21, 60.32, 60.458, 60.72, 60.731, 60.76 • Lung, transplantation, 60.458


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Lung transplantation is now considered acceptable therapy for many forms of end-stage lung disease. Single-lung transplantation is the most commonly performed procedure; as of the time this article was written, more than 5,400 single-lung transplantations had been performed worldwide (1). The most common indications for single-lung transplantation are chronic obstructive pulmonary disease, pulmonary fibrosis, and sarcoidosis (1). Most typical posttransplantation complications such as reperfusion edema, acute and chronic rejection, and infection occur either preferentially or exclusively in the allograft and have been well studied (2–7). Complications that preferentially involve the native lung, other than hyperinflation, have received less attention (8–11). The purposes of this study were to determine the incidence of native lung complications (excluding hyperinflation) in a large group of single-lung transplant recipients, characterize the radiologic features of these complications, and evaluate their clinical importance.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
During a 6-year period (1992–1999), 200 patients received lung transplants at our institution. Of these, 111 received single-lung transplants (on the right side in 70 and on the left in 41) and formed the study population. There were 57 women and 54 men, who ranged in age from 30 to 66 years (mean age, 55 years). Mean and median follow-up times were 24 and 18 months, respectively; 74 patients were alive at the time of our evaluation. Indications for transplantation were emphysema or chronic obstructive pulmonary disease (n = 86), pulmonary fibrosis (n = 15), sarcoidosis (n = 4), pulmonary hypertension (n = 2), pulmonary Langerhans cell histiocytosis (n = 2), rheumatoid lung (n = 1), and silicosis (n = 1).

At our institution, routine follow-up of lung transplant recipients includes chest radiography and surveillance fiberoptic bronchoscopy; computed tomography (CT) is not routinely performed. Chest radiographs are obtained daily during hospitalization, weekly during the 1st month after discharge, and at 3-month intervals thereafter. Bronchoscopy is performed 1, 3, 6, and 12 months after transplantation. Chest radiography, CT, or bronchoscopy with bronchoalveolar lavage or transbronchial biopsy is performed if patients develop clinical or radiologic abnormalities at any time after transplantation.

The clinical and radiologic records of the 111 patients were reviewed by a thoracic radiologist (H.P.M.) and pulmonary clinician (S.M.P.) for clinical and radiologic evidence of complications that primarily involved the nontransplanted hemithorax. Patients were included if the native lung or hemithorax was involved exclusively or was definitely involved first. Patients were excluded if the allograft was involved prior to or concomitant with native lung involvement. Hyperinflation of the native lung was not evaluated, since this was the subject of several prior studies (12–16), including one from our institution.

We identified 17 patients who satisfied the inclusion criteria. In these patients, medical records were further reviewed and complaints at presentation, results of cultures or histopathologic examination, diagnostic or therapeutic procedures, and patient outcomes were noted. The clinical importance of these complications was assessed by using specific end points, which included complete recovery without invasive therapy, complete recovery after invasive therapy, and death. The time between the diagnosis of the complication and the date of transplantation, onset of symptoms, development of new radiologic abnormalities, and specified end points were recorded.

In each of the 17 patients, all radiologic studies, which included chest radiographs, chest CT scans, and any additional images obtained at the time of diagnosis, were collectively reviewed by two experienced thoracic radiologists (H.P.M., J.J.E.), and findings were recorded with consensus. Chest radiographs, which were available in all patients, were first reviewed to confirm that the native lung was the primary site of disease. Initial chest radiographs were then reviewed for consolidation, nodule(s), cavitation, pleural fluid, hilar or mediastinal lymphadenopathy, or pneumothorax. Serial chest radiographs, which also were available in all patients, were assessed for progression or improvement of disease. Chest CT scans, obtained in eight patients, were reviewed for the same findings as the chest radiographs and for ground-glass opacity or endobronchial mass. 2-[Fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomographic (PET) scans (in two patients) were evaluated for uptake within lesion(s) that had been identified on chest radiographs or CT scans and within mediastinal or hilar lymph nodes. Bone scintigrams (in two patients) were reviewed, with notation of foci of abnormal radiotracer accumulation. Ventilation-perfusion (V-P) scans (in two patients) were reviewed, with notation of perfusion defects, and recorded as indicating high, intermediate, or low probability of pulmonary embolism by using the modified Prospective Investigation of Pulmonary Embolism Diagnosis, or PIOPED, criteria (17). Pulmonary arteriograms (in one patient) were reviewed for intraarterial filling defects.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Seventeen (15%) of 111 single-lung transplant recipients had a complication that primarily or exclusively involved the native lung or hemithorax. These complications occurred 0–58 months after transplantation (mean, 17 months) and included infection (n = 10), non–small cell lung cancer (n = 3), pulmonary embolism (n = 1), pulmonary infarction (n = 1), pneumothorax (n = 1), and nodules of unknown cause (n = 1). Infection was caused by bacteria (n = 4), fungi (n = 4), or mycobacteria (n = 2). Clinical and radiologic data are summarized in the Table.


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  		Clinical and Radiologic Features
 
Infection
Four patients developed bacterial pneumonia in the native lung; all had acute-onset fever, cough, and dyspnea at presentation. Chest radiographs obtained on the day of admission showed new homogeneous or heterogeneous lobar or segmental opacities that were confined to the native lung in all patients affected (Fig 1). Sputum cultures, also obtained on the day of admission, were positive for H influenzae bacteria in two patients and P aeruginosa bacteria in one. Sputum cultures were initially negative in the fourth patient, who, during the next week, developed an ipsilateral pleural effusion from which anaerobic organisms were cultured. Serial radiographs in three of the four patients showed that infection remained localized to the native lung; all three recovered completely, although tube thoracostomy for drainage of empyema was required in one. The fourth patient, who had P aeruginosa pneumonia, developed progressive bilateral opacities during the next 2 weeks and died of respiratory failure 3 weeks after admission and diagnosis.



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  		Figure 1. Patient 1. P aeruginosa pneumonia in a 60-year-old man with cough, fever, and dyspnea at presentation 26 months after right single-lung transplantation for emphysema. Transverse chest CT scan (10-mm collimation, lung window) shows severe emphysema in the native left lung and peripheral homogeneous opacity in the left lower lobe (arrows). Peribronchial opacities in the right lower lobe were unchanged from those seen at CT 2 months previously. Cultures of bronchoalveolar lavage fluid from the left lower lobe grew P aeruginosa bacteria. The patient subsequently died of respiratory failure.

 
Two patients developed mycobacterial infection in the native lung, one with M tuberculosis organisms and the other with M avium-intracellulare complex. Initial chest radiographs in the patient with tuberculosis showed new heterogeneous opacities in the lower lobe of the native lung (Fig 2). Cultures of bronchoalveolar fluid obtained from this lobe 2 days after admission grew M tuberculosis bacteria. Serial radiographs demonstrated progression to bilateral involvement 2 weeks after admission, and the patient died of respiratory failure after 1 month of antituberculous therapy. The patient with nontuberculous mycobacterial infection was asymptomatic at presentation; infection manifested on surveillance chest radiographs as new poorly defined upper-lobe nodules in the native lung. CT scans revealed two 1.0-cm nodules in the upper lobe of the native lung (Fig 3). A resected thoracoscopic wedge specimen obtained 2 months later showed granulomatous inflammation and acid-fast bacilli; cultures subsequently grew M avium-intracellulare complex. The patient recovered completely without further therapy.



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  		Figure 2. Patient 5. Tuberculosis in a 60-year-old man with cough, fever, and dyspnea at presentation 10 months after left single-lung transplantation for rheumatoid lung disease. Posteroanterior chest radiograph shows new heterogeneous opacities (arrows) in the native right lower lobe. Bilateral pleural thickening was unchanged from that seen on multiple prior radiographs. Cultures of bronchoalveolar lavage fluid from the right lower lobe were positive for M tuberculosis infection. The patient subsequently died of respiratory failure.

 


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  		Figure 3. Patient 6. Atypical mycobacterial infection in an asymptomatic 62-year-old woman with new radiographic abnormalities 16 months after right single-lung transplantation for emphysema. Transverse chest CT scan (10-mm collimation, lung window) shows severe emphysema in the native left lung and two small nodules in the left upper lobe (arrow). Resected thoracoscopic wedge specimen revealed granulomatous inflammation with numerous acid-fast bacilli. Cultures grew M avium-intracellulare complex.

 
Four patients developed fungal pneumonia in the native lung. All were acutely ill with fever, cough, and dyspnea at presentation; one also had hemoptysis. Chest radiographs obtained on the day of admission showed new homogeneous or heterogeneous lobar or segmental opacities that were confined to the native lung in all patients (Fig 4). In one patient, a diagnosis of Aspergillus pneumonia was made on the basis of sputum culture results alone because the patient was too ill to undergo fiberoptic bronchoscopy. This patient developed progressive bilateral opacities that were visible on serial chest radiographs and died 1 month later of respiratory failure. In two patients, a diagnosis of P boydii and Cladosporium species infection was made by culturing bronchoalveolar lavage fluid that was obtained within 3 days of admission. The patient with P boydii infection died of respiratory failure within 1 month of diagnosis; the patient with Cladosporium species infection recovered completely after a prolonged course of antifungal therapy. The fourth patient developed a cavitary mass with an air crescent sign on chest radiographs and CT scans (Fig 4). Rhizopus species infection was diagnosed at CT-guided needle aspiration biopsy performed 3 days after admission. The patient survived after undergoing lower lobectomy and systemic antifungal therapy.



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  		Figure 4a. Patient 10. Rhizopus species infection in a 53-year-old woman with cough, fever, and chest pain at presentation 2 months after right single-lung transplantation for emphysema. (a) Posteroanterior chest radiograph shows cavitary mass in the native left lower lobe (arrows). Opacities in the right lung (allograft) were unchanged from those seen on multiple prior radiographs. (b) Transverse chest CT scan (10-mm collimation, lung window) confirms a cavitary mass and an intracavitary mass (M) in the left lower lobe and shows the air crescent sign (arrow). CT-guided aspiration biopsy demonstrated Rhizopus species infection that was confirmed at resection of the left lower lobe.

 


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  		Figure 4b. Patient 10. Rhizopus species infection in a 53-year-old woman with cough, fever, and chest pain at presentation 2 months after right single-lung transplantation for emphysema. (a) Posteroanterior chest radiograph shows cavitary mass in the native left lower lobe (arrows). Opacities in the right lung (allograft) were unchanged from those seen on multiple prior radiographs. (b) Transverse chest CT scan (10-mm collimation, lung window) confirms a cavitary mass and an intracavitary mass (M) in the left lower lobe and shows the air crescent sign (arrow). CT-guided aspiration biopsy demonstrated Rhizopus species infection that was confirmed at resection of the left lower lobe.

 
Malignancy
Three patients, all former smokers, developed non–small cell cancer in the native lung; one admitted to continuing to smoke after transplantation. The first patient was asymptomatic at presentation; surveillance chest radiographs showed a new solitary upper lobe nodule (Fig 5). The patient underwent cervical mediastinoscopy and thoracoscopic wedge resection. All lymph nodes were negative, and the patient was alive without evidence of metastases 12 months after surgery. The second patient had cough and chest pain at presentation. Chest radiographs and CT scans revealed a hilar mass and lower lobe atelectasis. The patient underwent cervical mediastinoscopy and lower lobectomy. All lymph nodes were negative, and the patient was alive without evidence of metastases 6 months after surgery. The third patient had shoulder pain at presentation and was found to have a focal lesion of the right scapula on radionuclide bone scintigrams (Fig 6). Thoracic CT scans showed a lytic lesion of the scapula and multiple 1.0–2.0-cm nodules in the native lung. CT-guided transthoracic needle aspiration confirmed metastatic non–small cell cancer. The patient died of progressive malignancy 6 months later.



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  		Figure 5a. Patient 13. Stage I non-small cell lung cancer in an asymptomatic 56-year-old woman with new radiographic abnormalities 34 months after left single-lung transplantation for emphysema. (a) Posteroanterior chest radiograph shows a well-defined 1.5-cm nodule (arrow) in the native right upper lobe, which was confirmed at CT (not shown). This lesion was not present on surveillance radiographs that had been obtained 6 months earlier (not shown). (b) Coronal FDG-PET scan shows hypermetabolism within the right upper lobe nodule (arrow). No hypermetabolism is seen within hilar or mediastinal lymph nodes. The patient underwent mediastinoscopy and thoracoscopic wedge resection of a right upper lobe nodule. All mediastinal nodes were negative for malignancy. Histopathologic examination of the resected nodule confirmed adenocarcinoma. V = normal left ventricular activity.

 


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  		Figure 5b. Patient 13. Stage I non-small cell lung cancer in an asymptomatic 56-year-old woman with new radiographic abnormalities 34 months after left single-lung transplantation for emphysema. (a) Posteroanterior chest radiograph shows a well-defined 1.5-cm nodule (arrow) in the native right upper lobe, which was confirmed at CT (not shown). This lesion was not present on surveillance radiographs that had been obtained 6 months earlier (not shown). (b) Coronal FDG-PET scan shows hypermetabolism within the right upper lobe nodule (arrow). No hypermetabolism is seen within hilar or mediastinal lymph nodes. The patient underwent mediastinoscopy and thoracoscopic wedge resection of a right upper lobe nodule. All mediastinal nodes were negative for malignancy. Histopathologic examination of the resected nodule confirmed adenocarcinoma. V = normal left ventricular activity.

 


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  		Figure 6a. Patient 12. Stage IV non-small cell lung cancer in a 57-year-old man with severe right shoulder pain at presentation 9 months after left single-lung transplantation for pulmonary fibrosis. Posteroanterior chest radiograph (not shown) showed only end-stage fibrosis in the native right lung and no pulmonary nodules. (a) Posterior technetium 99m methylene diphosphonate bone scan shows a focal area of increased radiotracer uptake in the scapula (straight arrow). There is a second focus in the left posterior sixth rib (curved arrow). (b) Transverse chest CT (10-mm collimation, bone window) scan obtained with the patient in a prone position for biopsy shows fibrosis and multiple nodules (arrows) in the native right lung. Transthoracic needle aspiration of the scapula confirmed metastatic non-small cell cancer.

 


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  		Figure 6b. Patient 12. Stage IV non-small cell lung cancer in a 57-year-old man with severe right shoulder pain at presentation 9 months after left single-lung transplantation for pulmonary fibrosis. Posteroanterior chest radiograph (not shown) showed only end-stage fibrosis in the native right lung and no pulmonary nodules. (a) Posterior technetium 99m methylene diphosphonate bone scan shows a focal area of increased radiotracer uptake in the scapula (straight arrow). There is a second focus in the left posterior sixth rib (curved arrow). (b) Transverse chest CT (10-mm collimation, bone window) scan obtained with the patient in a prone position for biopsy shows fibrosis and multiple nodules (arrows) in the native right lung. Transthoracic needle aspiration of the scapula confirmed metastatic non-small cell cancer.

 
Pulmonary Embolism or Infarction
Two patients had pulmonary embolism or infarction that involved the native lung. The first patient had acute dyspnea at presentation 2 months after transplantation. V-P scans were interpreted as indicating intermediate probability for pulmonary embolism; pulmonary arteriograms showed thrombus in the native lower lobe artery. The patient recovered uneventfully after systemic anticoagulation. The second patient underwent single-lung transplantation for pulmonary hypertension and developed progressive peripheral opacification of the native lung, which was depicted on chest radiographs and CT scans. V-P scans obtained 10 days after transplantation showed markedly decreased perfusion to the native lung when compared with perfusion scans that were obtained immediately after transplantation. The patient developed hemodynamic instability, which was presumed to be due to native lung infarction and sepsis, and underwent pneumonectomy. Examination of the resected specimen showed diffuse hemorrhage and edema that were consistent with in situ pulmonary infarction; no clot was found in the central pulmonary arteries. The patient was discharged after prolonged hospitalization and recovered completely.

Miscellaneous Complications
One patient had acute onset of dyspnea and chest pain at presentation. Chest radiographs revealed a large pneumothorax contralateral to the transplant. The pneumothorax resolved after tube thoracostomy and did not recur. One patient who was asymptomatic had developed new poorly defined clustered nodules in the superior segment of the lower lobe at surveillance chest radiography that were confirmed at CT. FDG-PET scans showed increased metabolic activity in the lesions. The results of all cultures and transbronchial biopsy were negative for organisms or malignancy. The patient was treated with broad-spectrum antibiotics, and the lesions resolved within 3 months.

Clinical Importance
Five (29%) of the 17 patients died of complications that originated in the native lung. Four of the five patients’ deaths were due to infection; one was due to malignancy. The remaining 12 patients recovered. However, seven of these patients underwent one or more additional invasive procedures for diagnosis or treatment. Three underwent mediastinoscopy for staging presumed lung cancer. Two underwent lobectomy for resection of lung cancer (n = 1) or pulmonary mucormycosis (n = 1). Two underwent thoracoscopic wedge resection for diagnosis of small pulmonary nodules (M avium-intracellulare complex infection, [n = 1]) or resection of cancer (n = 1). Two required tube thoracostomy for drainage of empyema (n = 1) or pneumothorax (n = 1). One required pneumonectomy for removal of an infarcted native lung.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Most complications occurring after single-lung transplantation, such as acute graft dysfunction, reperfusion edema, acute and chronic rejection, and stenosis at the bronchial anastomosis, occur exclusively in the allograft. Other complications such as posttransplantation lymphoproliferative disorder and infection occur more frequently in the allograft than in the native lung (9,18). Complications related specifically to the native lung have been reported to occur in up to 25% of patients after single-lung transplantation (10). In our experience, native lung complications after single-lung transplantation occurred less frequently (in 17 [15%] of 111 patients) than previously reported. However, when these complications occurred, they were associated with high morbidity and mortality.

Infection remains a common posttransplantation complication and a major cause of morbidity and mortality in lung transplant recipients (1). Between 50% and 60% of these patients develop pneumonia after transplantation, and their risk of infection is 1.5–10 times greater than that in other solid-organ transplant recipients. The allograft is infected more commonly than the native lung after single-lung transplantation because of impaired mucociliary clearance and interrupted lymphatic drainage in the graft and denervation of the graft that results in loss of the cough reflex (19,20). Our experience suggests that, although infection in the native lung is not as common as infection in the allograft, it can be associated with high morbidity and mortality. Infection accounted for 10 (59%) of 17 serious native lung complications in our series and four of the five deaths. Although the overall incidence of infection in the native lung in our series was higher than that reported by Venuta et al (11), the high morbidity and mortality of these infections were similar between series. In our series, bacterial pathogens accounted for four (40%) of 10 infections; opportunistic fungal pathogens, for four (40%) of 10. The remainder were caused by mycobacteria. We find it interesting that we observed no native lung infections due to cytomegalovirus or respiratory viruses—pathogens that often cause infection in lung transplant recipients (7,21).

Although bacterial pneumonia in the lung transplant recipient population is usually caused by Staphylococcus aureus or gram-negative organisms (19,20), two of the four bacterial pneumonias in our series were caused by H influenzae. In addition, although the incidence of bacterial pneumonia in the transplant recipient population is highest in the 1st month after transplantation (19), all cases of bacterial pneumonia in our series occurred more than 1 year after transplantation. Patients with bacterial pneumonia in the native lung at presentation typically had, as expected, acute onset of cough, fever, and dyspnea. Chest radiographs showed focal heterogeneous or homogeneous opacities in a segmental or lobar distribution.

Although immunosuppression increases the risk of mycobacterial infection, tuberculous and nontuberculous mycobacterial infection are uncommon in the lung transplant recipient population (22–24). Mycobacterial infection has been reported as a consequence of donor-to-recipient transmission and as occurring after the augmentation of systemic steroids; however, it can occur de novo (22,24–26). Infection usually occurs in the 1st 3 months after transplantation and has a variety of radiologic manifestations, which include homogeneous and scattered heterogeneous opacities, cavitary lesions, multiple nodular pulmonary opacities, hilar lymphadenopathy, and pleural effusion (22,24–26). Similar to other reported lung transplant recipients with tuberculosis, the patient in our study had symptoms at presentation (22–26). However, the patient in our study who had tuberculosis died of progressive infection, whereas most patients who are affected respond well to standard antituberculous therapy (24).

Fungal pneumonia is less common than either bacterial or cytomegalovirus pneumonia in most series and rarely occurs in the 1st month after transplantation (19,27). It is, however, associated with high mortality that is often greater than 50% (19,27). The most common fungal pathogens in the lung transplant recipient population are Aspergillus and Candida species (28,29). However, three of the four fungal pneumonias in the patients in our series were caused by less common opportunists, which include P boydii and Rhizopus (mucormycosis) species. Our experience emphasizes the high morbidity and mortality of fungal infection in this population. Two (50%) of the four patients who were affected died, and lobectomy was required in one (50%) of the two patients who survived.

It is unfortunate that the radiographic appearance and clinical presentation of fungal pneumonia greatly overlapped that of tuberculosis and bacterial pneumonia in the patients in our series. Diagnosis of fungal pneumonia therefore requires a high index of suspicion. Confident diagnosis can be difficult, however, because many of these organisms may colonize the donor lung. Although positive sputum or bronchoalveolar lavage smears and cultures are suggestive, definitive diagnosis of invasive fungal infection may require biopsy (27).

Non–small cell lung cancer has been reported as an uncommon finding in the native lung after single-lung transplantation (10,30,31). However, the true incidence is uncertain because of the small number of patients included in studies and the relatively short follow-up period. Although immunosuppression predisposes lung transplant recipients to developing posttransplantation lymphoproliferative disorder, to our knowledge, there is no evidence to suggest an increase in non–small cell lung cancer in this group (31,32). In our series, non–small cell cancers that originated in the native lung proved to be an important, although uncommon, native lung complication. Two patients with emphysema were found to have resectable malignancies (stage I). A third patient, who had fibrosis, was found to have unresectable disease (stage IV). In the former patients, the abnormalities were easily detectable on serial chest radiographs, given the background of emphysematous lung. In the third patient, however, diagnosis may have been delayed because the pulmonary nodules were obscured by fibrotic lung. At retrospective review of the pretransplantation chest CT scans, which were obtained 20, 23, and 44 months prior to diagnosis of malignancy, no lung nodules were seen in these three patients.

There were no cases of posttransplantation lymphoproliferative disease involving the native lung in our series. This was in keeping with reports (18,33) that, in single-lung transplant recipients, posttransplantation lymphoproliferative disease typically occurs in the allograft; the native lung is rarely involved unless disease is widely disseminated.

Two patients in our series had pulmonary vascular complications. One patient had pulmonary emboli in the native emphysematous lung. Investigators in a few studies have specifically addressed the issue of pulmonary embolism in lung transplant recipients. In a large retrospective series, Kroshus and colleagues (34) found that seven (6%) of 116 lung or heart-lung transplant recipients received a diagnosis of pulmonary emboli during a 7-year period. Three (43%) of these patients died. Although most of the patients with pulmonary emboli had received single-lung transplants, the side on which emboli occurred (native lung vs allograft) was not specified.

Because blood flow is preferentially directed toward the allograft after single-lung transplantation, most emboli should, in theory, lodge in the allograft, so diagnosis of a new perfusion defect at V-P scanning should be relatively straightforward (35). Diagnosis of emboli in the native lung, however, may be more difficult because of underlying lung disease and preexistent V-P mismatch in the native lung. Unless comparison studies are available, V-P scans may be difficult to interpret in this setting (34). CT or conventional pulmonary angiography may then be required for definitive diagnosis. Our experience and that of others (10,11) emphasize either the rarity or the difficulty of diagnosing pulmonary embolism in the native lung. One patient in our series developed infarction of the native lung after single-lung transplantation for pulmonary arterial hypertension, perhaps because of extreme shift in blood flow to the allograft. This appears to be a very rare complication after single-lung transplantation for pulmonary hypertension (8,36,37).

Hyperinflation of the native lung is the one complication that occurs exclusively in the native lung after single-lung transplantation. We did not evaluate hyperinflation of the native lung in this study. However, in a prior study from our institution, Malchow and colleagues (13) found that 50% of patients with emphysema who were treated with single-lung transplantation had progressive hyperinflation of the native lung on postoperative radiographs. Their data and those of other investigators (14,15,38) suggest that severe hyperinflation of the native lung may adversely affect graft function by compressing the graft and increasing pulmonary vascular resistance. Such patients may have clinical improvement after contralateral lung volume reduction surgery (14,15,38). However, in some instances, native lung hyperinflation may be a compensatory phenomenon due to graft fibrosis that is caused by infection or chronic rejection. Identifying which patients with native lung hyperexpansion will benefit from lung volume reduction surgery has proved to be a difficult task, however (12,16).

Our study had several limitations. First, because it was a retrospective study in which clinical and radiologic records were used to identify patients, it is possible that some patients with native lung complications were not included. However, given the intense clinical and radiologic surveillance of these patients, it is unlikely that clinically important complications, particularly those leading to hospitalization, were excluded. Second, because physicians at our institution preferentially treat patients with lymphangioleiomyomatosis by performing bilateral, not single, lung transplantation, complications such as pneumothorax or chylous effusion were probably underrepresented in our study (39). A multiinstitutional study might have had different results in this regard. Third, because we did not specifically evaluate allograft complications in our patients, we could not, strictly speaking, compare the frequency of complications in the native lung with that in the allograft. It is clear, however, from our experience and the extensive literature on the subject (3,4, 6,7,21,40–48), that the frequency of clinically important complications in the native lung pales in comparison with that in the allograft.

In summary, our experience emphasizes the importance of native lung complications in single-lung transplant recipients. Although probably uncommon when compared with complications affecting the allograft, native lung complications can lead to major morbidity and mortality. In our series, infection and non–small cell lung cancer were the most common native lung complications. Non–small cell lung cancer is a particular concern in this population because most single-lung transplant recipients are former smokers with emphysema.


   FOOTNOTES
 
Abbreviations: FDG = 2-[fluorine-18]fluoro-2-deoxy-D-glucose, V-P = ventilation-perfusion

Author contributions: Guarantor of integrity of entire study, H.P.M.; study concepts and design, H.P.M., S.M.P.; definition of intellectual content, H.P.M., J.J.E.; literature research, H.P.M., J.J.E.; clinical studies, H.P.M., S.M.P.; data acquisition, H.P.M., S.M.P.; data analysis, H.P.M.; manuscript preparation and editing, H.P.M., J.J.E.; manuscript review, H.P.M., J.J.E., S.M.P.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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