Four-year prospective study of pulmonary venous thrombosis after lung transplantation.

The objective of this study was to prospectively assess pulmonary venous anastomosis by transesophageal echocardiography after lung transplantation. Thrombus formation at the pulmonary venous anastomotic site after lung transplantation may have catastrophic consequences, including allograft failure and stroke. Eighty-seven consecutive adult lung transplant recipients underwent transesophageal echocardiography within 48 hours after surgery. Thrombosis of a pulmonary vein was diagnosed in 13 (15%) of 87 patients in the early postoperative period after lung transplantation. Mean thrombus width was 0.9 +/- 0.4 cm (range, 0.5 to 1.7 cm), with an average peak flow velocity at the site of obstruction of 127 +/- 23 cm/s (range, 90 to 150 cm/s). Five patients with pulmonary vein thrombosis died in the perioperative period, yielding a 90-day mortality rate of 38%. Larger thrombus size and greater acceleration of flow through a narrowed pulmonary vein correlated with poor clinical outcome. During each year of the study, the incidence of pulmonary vein thrombosis declined progressively. Pulmonary vein thrombosis is a potentially ominous complication in the early postoperative period after lung transplantation. Transesophageal echocardiography is a valuable tool for detecting abnormalities of the pulmonary venous anastomosis. Thrombus size and flow velocity at the anastomotic site may guide prognosis and clinical management. Complications of the pulmonary venous anastomosis are in part technical in nature.

Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation.

Obliterative bronchiolitis (OB) after lung transplantation is the end result of multiple immunologic, virologic, genetic, and environmental effects on the transplanted lung. In this study, we first analyzed risk factors for OB in a single-center population of 152 lung transplant recipients. We then examined the influence of donor and recipient HLA mismatching on progression to OB, and on the identified risk factors for OB. The median time to onset of OB for the entire study population was 2.7 yr. The significant risk factors for OB by multivariate analyses were grade A2 or A3 acute rejection (p = 0.0126) and cytomegalovirus (CMV) pneumonitis (p = 0.0358). The only significant HLA risk factor for OB was mismatching at the HLA-A locus (p = 0.0144). On the basis of Cox proportional hazards modeling, a predictive formula was derived to estimate the risk of OB after lung transplantation. Although mismatching at the HLA-DR locus was a significant risk factor for CMV pneumonitis in recipients exposed to CMV before transplantation (p = 0.0199), and protected against acute rejection, it did not independently protect against OB. These results indicate that HLA mismatches between donors and recipients significantly influence the development of OB both directly, and indirectly, by influencing the major risk factors for OB.

Superiority of end-to-end versus telescoped bronchial anastomosis in single lung transplantation for pulmonary emphysema.

OBJECTIVE: To assess the influence of surgical technique (telescoped versus end-to-end anastomosis) on the incidence of bronchial anastomotic complications in patients who underwent single lung transplantation for pulmonary emphysema. METHODS: Seventy-six adult recipients of single lung transplants for pulmonary emphysema were evaluated for the presence of 3 types of major bronchial anastomotic complications: ischemia, dehiscence, and severe stenosis. Surgical technique, clinical course, and mortality were reviewed retrospectively. RESULTS: The 3 major complications were observed in 11 (34%; ischemia), 8 (25%; dehiscence), and 11 (34%; severe stenosis) of 32 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis occurred in only 4 (9%), 1 (2%), and 2 (5%) of 44 end-to-end anastomoses (P =.0087, P =.0034, and P =.0012, respectively). The relative risk of ischemia, dehiscence, and severe stenosis in telescoped anastomoses was 2.1, 2.5, and 2.5, respectively, compared with end-to-end anastomoses. Five (13%) telescoped anastomoses required stent placement as compared with only 2 (5%) end-to-end anastomoses (P =.1244). Early postoperative pneumonia was more common in the telescoped anastomosis group (56%) than in the end-to-end group (32%; P =.0380). There was a trend toward shorter survival in the telescoped anastomosis group (mean survival 1045 +/- 145 days) as compared with the end-to-end group (mean survival 1289 +/- 156 days), but these differences did not achieve statistical significance (P =.2410). CONCLUSIONS: In patients who underwent single lung transplantation for pulmonary emphysema, telescoped anastomoses were associated with a higher incidence of bronchial anastomotic complications than end-to-end anastomoses.

Pulmonary nodules and masses after lung and heart-lung transplantation.

The authors assess clinical and radiographic findings of pulmonary nodules and masses after lung and heart-lung transplantation. One hundred and fifty nine patients who survived at least 3 months after lung and heart-lung transplantation were followed by serial chest radiographs for a median of 27 months. Single or multiple lung nodules or masses were noted at chest radiography in 15 (9.4%) of 159 patients. Imaging findings and causes of these nodules and masses were reviewed retrospectively. Infection was found in 10 (6%) of 159 patients. Specific pathogens (11 pathogens in 10 patients) were Aspergillus (n = 4), Mycobacteria (n = 4), and other bacteria (n = 3). Noninfectious causes were found in 5 (3%) of patients and included B-cell lymphoma (n = 2), bronchogenic carcinoma (n = 2), and pulmonary infarcts (n = 1). Nodules and masses appeared a median of 11 months after transplantation (range: 0.2 to 36 months). Five patients (33%) had single lesions; the other 10 (67%) patients had multiple lesions (range 2 to 50). Aspergillus lesions were most commonly located in the upper lobes, were cavitary in three of four patients, and all were fatal. Nodules and masses arose in the transplanted lung in 12 (80%) of the patients, and in the native lung in 3 (20%) of the patients (2 bronchogenic carcinoma, 1 M. tuberculosis simulating bronchogenic carcinoma). Nodules and masses detected by chest radiography are not uncommon (9.4%) after lung and heart-lung transplantation. Infections are more common than noninfectious causes of posttransplant nodules and masses. Specific clinical and imaging characteristics may provide clues to etiology.

Deleterious effects of telescoped bronchial anastomosis in single and bilateral lung transplantation.

PURPOSE: To compare complication rates of telescoped versus end-to-end bronchial anastomoses in single and bilateral lung transplantation. METHODS: One hundred and thirty adult lung transplant recipients were evaluated during a seven-year period for the presence of three types of major bronchial anastomotic complications (ischemia, dehiscence, and severe stenosis). Surgical technique, clinical course, and mortality in all patients were reviewed retrospectively. RESULTS: The three major complications, ischemia, dehiscence, and severe stenosis, were observed in 13 (32%), 10 (24%), and 13 (32%), respectively, of 41 telescoped bronchial anastomoses. In contrast, ischemia, dehiscence, and severe stenosis, occurred in 25 (19%), 14 (10%), and 11 (8%) of 135 end-to end anastomoses. These differences were statistically significant for the occurrence of dehiscence and severe stenosis (p=0.0350 and 0.0004, respectively), and not statistically significant for ischemia (p=0.0846). Five (12%) telescoped anastomoses required stent placement as compared with six (4%) end-to end anastomoses (p=0.1313). Early postoperative pneumonia was more common in the telescoped anastomosis group (57%) as compared to the end-to-end group (35%; p=0.0271). There was a trend to shorter survival in the telescoped anastomosis group (mean survival 1172+/-149 d) as compared to the end-to-end group (mean survival 1542+/-126 d), but these differences did not achieve statistical significance (p=0.2400). CONCLUSION: In single and bilateral lung transplants, telescoped anastomoses are associated with a higher incidence of bronchial anastomotic complications and postoperative pneumonia than end-to-end anastomoses.

Influence of lung injury on early postoperative survival after lung transplantation.

OBJECTIVES: To identify the various risk factors for early (90 day) mortality after lung transplantation and to evaluate the relationship between lung injury and postoperative survival. METHODS: 152 recipients of single (100) or bilateral (52) lung allografts were evaluated for the presence of postoperative lung injury assessed by a composite four-component lung injury score. Preoperative variables, postoperative course, and mortality were reviewed retrospectively. RESULTS: There was a high risk of death during the first 90 d after transplantation, followed by a decline in risk during the remainder of the first postoperative year. By univariate analysis, lung injury score (p = 0.0001), chest radiograph score (p = 0.0001), and hypoxemia (PaO2/FIO2) ratio (p = 0.0002) were the most statistically significant risk factors for 90-day mortality. Other parameters such as length of intensive care stay (p = 0.0175), length of intubation (p = 0.0212), and preoperative diagnosis of pulmonary fibrosis (p = 0.0123) were also significant risk factors for 90-day mortality. By multivariable analysis, only lung injury score (p = 0.0001) was a statistically significant risk factor for 90-day mortality. The risk of 90-day mortality increased by a factor of 4.4 for each 1 point increment in lung injury score. However, none of the analyzed preoperative or postoperative variables were able to statistically predict lung injury score. CONCLUSIONS: Postoperative lung injury is the most important risk factor for early postoperative mortality after lung transplantation.

Insufficiency fractures of the sacrum: a cause of low back pain after lung transplantation.

Insufficiency fractures of the sacrum were diagnosed during the first year after successful transplantation in four (5.6%) of 71 lung and heart-lung transplant recipients. Each patient had development of low back pain after minor or no trauma; all had osteoporosis. In each instance, plain radiographs failed to demonstrate the fracture, and the diagnosis was established by radionuclide bone scanning that demonstrated the characteristic "butterfly" (bilateral sacral fracture) or "half-butterfly" appearance (unilateral sacral fracture). Sacral insufficiency fractures, a significant cause of low back pain in lung transplant recipients, may be underdiagnosed in this population because routine radiographs do not usually reveal the fracture; bone scanning is the preferred diagnostic modality.

Late pulmonary venous complications after lung transplantation.

Although abnormalities of the pulmonary venous anastomosis in the early postoperative period after lung transplantation have been reported from several centers, late complications related to the pulmonary venous anastomosis have not been described. In the present study, we describe the clinical and transesophageal echocardiographic findings of pulmonary vein anastomotic complications in two patients at 1.9 and 2.3 years after lung transplantation. Both pulmonary venous abnormalities, stenosis in the first instance and thrombosis in the second instance, impaired venous outflow on the affected side causing unilateral edema and pleural effusion. Pulmonary venous abnormalities late after lung transplantation can mimic allograft rejection, opportunistic infection, or heart failure and are best diagnosed by transesophageal echocardiography.

Pulmonary tuberculosis after lung transplantation.

During a 5-year study period, we diagnosed pulmonary tuberculosis in two (2%) of 94 lung and heart-lung transplant recipients. Each infection occurred 3 months after bilateral lung transplantation in the presence of evidence implicating donor-to-recipient transmission of the pathogen. The radiographic patterns of pulmonary tuberculosis were subtle: narrowing of the middle lobe bronchus of the right lung caused by an endobronchial granulomatous mass (n = 1) and a focal cluster of small nodules in the upper lobe of the left lung and small bilateral pleural effusions (n = 1). Each patient achieved complete clinical and radiographic response after antituberculous therapy. We conclude that Mycobacterium tuberculosis may be transmitted directly by a donor lung and may involve bronchial mucosa, pulmonary parenchyma, and pleura.

Adhesion molecules (E-selectin and ICAM-1) in pulmonary allograft rejection.

Vascular endothelial cells act as antigen-presenting cells in the lung allograft and stimulate alloreactive host lymphocytes. Activated lymphocytes and cytokines can induce expression of leukocyte-endothelial adhesion molecules that facilitate invasion of the allograft by circulating leukocytes. To define the role of endothelial HLA class II antigen and adhesion molecule expression in lung allograft rejection, we prospectively analyzed endothelial expression of HLA class II, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) antigens in 52 transbronchial biopsy specimens from 24 lung allograft recipients as compared to normal control subjects. Thirty-one of 52 specimens showed histologic rejection and 8 of 24 patients developed histologic obliterative bronchiolitis (OB) by the end of the study period. Increased expression of HLA class II antigen was seen in 32 of 52 (62%) lung allograft specimens, but increased expression did not correlate with acute rejection or OB. In contrast, E-selectin expression was seen in 30 of 52 (58%) biopsy specimens and was associated with acute rejection (p < 0.005) and with the development of OB (p < 0.05). Increased expression of ICAM-1 was seen in only 18 of 52 (35%) biopsy specimens and did not correlate with acute rejection or OB. These data suggest that E-selectin expression may be a tissue marker of acute and chronic lung rejection possibly by promoting leukocyte adhesion to the allograft endothelium. The high levels of endothelial HLA class II expression may reflect long-term antigenic stimulation of the allograft even in the absence of rejection.

Variability of right ventricular functional recovery after lung transplantation.

BACKGROUND: The purpose of this study was to assess by echocardiography the effects of lung transplantation on recovery of right ventricular (RV) function in patients with preoperative RV dysfunction. METHODS: Fourteen (20%) of 71 lung transplant recipients were identified by echocardiography as manifesting abnormal RV function before lung transplantation. These 14 patients were selected for follow-up echocardiographic study 8 months after transplantation. RESULTS: RV function improved significantly in the study group. Mean RV end-diastolic area decreased from 26.8 +/- 7.9 cm2 to 20.1 +/- 4.7 cm2 (P < 0.01); mean RV end-systolic area decreased from 21.5 +/- 6.8 cm2 to 13.1 +/- 4.2 (P < 0.01); and mean RV fractional area change (FAC) increased from 20.4 +/- 3.3% to 35.8 +/- 8.9% (P < 0.001). A subgroup of four patients, however, exhibited no change in RV function. Patients who achieved improvement in RV function tended to be younger, had shorter duration of disease before transplantation, and had higher pulmonary arterial (PA) pressures before transplantation (PA systolic, 89 +/- 28 mmHg vs. 38 +/- 11 mmHg, P < 0.001; PA diastolic, 42 +/- 11 mmHg vs. 19 +/- 3 mmHg, P < 0.002). Each of the eight patients with primary pulmonary hypertension exhibited improvement in RV function (mean delta FAC +20.6 +/- 5.9%), while two of three patients with emphysema and both patients with idiopathic pulmonary fibrosis failed to achieve improvement in RV function (mean delta FAC +2.3 +/- 1.2%). CONCLUSIONS: Improvement of RV function assessed by echocardiography occurs after lung transplantation, even in patients with severe preoperative RV dysfunction. However, the degree of improvement is variable and may depend on the degree of RV after-load reduction and the presence or absence of intrinsic myocardial disease. RV ejection parameters do not distinguish between these two possibilities.

Opportunistic bronchopulmonary infections after lung transplantation: clinical and radiographic findings.

PURPOSE: To assess clinical and radiographic findings in opportunistic bronchopulmonary infections after lung transplantation. MATERIALS AND METHODS: Forty-five episodes of opportunistic bronchopulmonary infection occurred in 27 (35%) of 77 lung transplant recipients during a 4-year period. Causative organisms, radiographic patterns, and mortality were reviewed. RESULTS: Cytomegalovirus (CMV) was the most common pathogen (25 episodes), followed by Aspergillus species (seven episodes), Pneumocystis carinii (six episodes), herpes simplex virus (four episodes), Mycobacterium avium complex (two episodes), and M tuberculosis (one episode). Eighteen of the 25 episodes (72%) of CMV pneumonitis occurred in the first 4 months after transplantation; 24 (96%) occurred within the 1st year. Radiographic patterns of symptomatic CMV pneumonitis were diffuse haziness (60%), focal haziness (33%), and focal consolidation (7%). Aspergillus species locally invaded a necrotic bronchial anastomosis in three patients, each within 4 months of transplantation. P carinii was seen as focal haziness and caused no symptoms. Radiographic findings, when present, were seen almost exclusively in the transplanted lung. Despite three deaths attributable to opportunistic bronchopulmonary infection, the difference between the survival rates of patients with and those of patients without bronchopulmonary infection was not statistically significant (82% and 81%, respectively, 1 year after transplantation). CONCLUSION: Opportunistic bronchopulmonary infections are common after lung transplantation. The most common pathogen is CMV, which causes diverse chest radiographic patterns. Opportunistic bronchopulmonary infections do not adversely affect overall mortality.

Incidence of pulmonary vein complications after lung transplantation: a prospective transesophageal echocardiographic study.

OBJECTIVES: This study attempted to document the incidence of pulmonary vein complications and their potential relation to clinical outcome in patients after lung transplantation. BACKGROUND: Several case reports have documented the presence of pulmonary venous thrombosis causing graft failure in patients after lung transplantation. Because the presentation of these complications mimics that of other postoperative problems, the true incidence of pulmonary vein abnormalities remains unclear. Transesophageal echocardiography is ideally suited to examine the pulmonary veins in the postoperative setting. METHODS: Twenty-one consecutive patients undergoing lung transplantation at our institution underwent transesophageal echocardiography within 32 days of transplantation (mean [+/- SD] 6.5 +/- 7.8 days). Special attention was placed on visualizing the pulmonary veins. RESULTS: Six (29%) of the 21 patients were noted to have abnormalities of the pulmonary veins in the vicinity of the anastomotic site. After follow-up of 30 days, 4 of these patients (67%) had significant cardiovascular morbidity, and 2 died, compared with 1 (7%) of 15 patients with normal pulmonary veins (p = 0.03). The degree of obstruction of the pulmonary vein appeared to correlate with short-term outcome. CONCLUSIONS: Abnormalities of the pulmonary veins are common after lung transplantation and are easily identified by transesophageal echocardiography. Occlusive thrombi appear to be detrimental to short-term outcome.

Coronary angiography in smokers undergoing evaluation for lung transplantation: is routine use justified?

Many patients referred for lung transplantation have a history of smoking. For the exclusion of the possibility of asymptomatic coronary artery disease, these patients undergo coronary angiography as part of their preoperative evaluation. The usefulness of this approach remains unknown. We reviewed the records of all smokers referred for lung transplantation who underwent coronary angiography (n = 77). Nine patients (12%) had significant coronary artery disease; six (8%) of these patients had their clinical management altered because of findings on angiography. Eight of nine patients with coronary artery disease (89%) and all of the six patients (100%) whose management was altered had coronary artery disease risk factors other than a history of smoking; therefore, no patient with clinically significant coronary artery disease had history of smoking as the only risk factor. The presence of other coronary artery disease risk factors was significantly associated (p < 0.0001) with the positive findings on angiography. A nonsignificant trend toward older age was found, and a higher proportion of male patients existed in the group with coronary artery disease. Routine angiography for all patients with a history of smoking referred for angiography is unjustified. A subset of patients with high risk identified primarily by the presence of additional coronary artery disease risk factors may benefit from routine angiography.