Assessment of survival benefit after lung transplantation by patient diagnosis.

BACKGROUND: Lung transplantation has become an established procedure for treating patients with endstage lung disease, resulting in broadening criteria for recipient selection. The survival benefit for some patient groups has yet to be established. METHODS: We reviewed 653 patients accepted for lung transplantation at our center. Patients were categorized into 6 diagnosis groups: cystic fibrosis (174), obstructive lung disease (163), pulmonary fibrosis (100), Eisenmenger's syndrome (76), pulmonary hypertension (68), bronchiectasis (51), and other (21). Using Cox regression, we estimated the time at which early operative risk of death fell below pre-operative risk levels (crossover point) and the point at which early high post-operative risk was offset by later low risk (equity point). The relative benefits of single lung vs double lung/heart-lung transplantation were assessed for patients with obstructive lung disease and pulmonary fibrosis. RESULTS: Post-operative risk of death fell below pre-operative risk levels for all diagnosis groups, indicating a survival advantage. The equity point was achieved for all distinct diagnosis groups (except Eisenmenger's); this survival benefit was significant for patients with obstructive lung disease, cystic fibrosis, and pulmonary hypertension. Single lung vs double lung/ heart-lung comparisons showed no significant difference in survival benefit. CONCLUSION: All survival benefit patient groups achieve after lung transplantation, with the exception of patients with Eisenmenger's syndrome, who may have prolonged survival while listed. Differences in survival benefit between single lung and double or heart-lung transplantation are not significant for patients with obstructive lung disease or pulmonary fibrosis.     

Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation.

OBJECTIVE: Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation. METHODS: Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg. RESULTS: Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure. CONCLUSIONS: Severe PTRI increased short-term morbidity and mortality. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia. The use of aprotinin in the perioperative patient management in lung transplantation had strong beneficial effects on the patient outcomes and decreased the incidence of post-transplant ischemia-reperfusion injury significantly.     

Outcome of infants listed for lung or heart/lung transplantation

BACKGROUND: Little is known about outcome, characteristics, or organ availability for infants listed for lung or heart/lung transplantation. METHODS: Within a 45-month period at one institution, all pediatric patients who were listed for primary lung or heart/lung transplantation and who reached the end point of either transplant or death prior to transplant were identified. Outcomes for those patients listed as younger than and older than 1 year of age were compared. RESULTS: Among 48 pediatric patients, 19 were infants less than one year of age. The median age among infants at listing was 3.7 months (range 0.5 to 8.9 months). Death before transplant occurred in 10 of 19 infants (53%) compared with 14 of 29 (48%) children. When comparing those infants who died prior to transplant with those who received organs, there were no significant differences with respect to size, blood type, age at listing, presence of pulmonary hypertension, or type of transplant for which the patient was listed. There was a trend toward poorer pre-transplant survival for infants when compared with children. Waiting times were significantly shorter for infants vs children (p = 0.02). The incidence of acute cellular rejection and serious infection was similar in the 2 groups. Infants had significantly longer hospitalization post-transplant and a trend toward poorer hospital survival, although survival at 1 year was comparable between the 2 groups. CONCLUSION: The outcome for infants listed for lung or heart/lung transplantation is similar to that of children; thus, very young age should not be considered a contraindication to lung or heart/lung transplantation. Earlier diagnosis and listing may decrease pre-transplant mortality.     

Association of lung perfusion disparity and mortality in patients with cystic fibrosis awaiting lung transplantation.

BACKGROUND: The risk of death for patients with end-stage cystic fibrosis awaiting lung transplantation remains high and most patients succumb to respiratory failure. This study was conducted to evaluate the usefulness of ventilation-perfusion scintillation scans, obtained during the pre-transplant period, to identify patterns that predict prognosis while on the waiting list. These patterns were compared with other pulmonary physiologic markers of ventilation and perfusion obtained from pulmonary function and cardiopulmonary exercise tests. METHODS: From November 1990 to January 1999, 46 patients with cystic fibrosis were listed for bilateral lung transplantation. Fourteen (30.4%) died while waiting for a transplant (Group 1), whereas 32 were transplanted successfully or remain alive and waiting (Group 2). Mean arterial blood gas values, Brasfield radiograph scores, cardiopulmonary exercise data and the degree of scintillation scan abnormalities between lungs were compared for each group. RESULTS: Mean survival for Group 1 was 10.2 +/- 1.7 months, and for Group 2 was 23.5 +/- 3.0 months (p < 0.001). The right upper lung zone was the most severely affected segment. The Cox proportional hazards model revealed an increased perfusion disparity and resting hypercapnia as the main predictors of death while on the transplant list. The Kaplan-Meier analysis indicated greater survival for the groups with <30% disparity between lungs on the pre-transplant scintillation scans. CONCLUSIONS: The results suggest that severe, unilateral perfusion abnormalities seen on scintillation scans in patients with cystic fibrosis are associated with an increased risk of dying while on the lung transplant waiting list and may be helpful in identifying patients who should be considered for early or living-donor transplantation.     

Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation.

BACKGROUND: At many lung transplant centers, right heart catheterization and transthoracic echocardiogram are part of the routine pre-transplant evaluation to measure pulmonary pressures. Because decisions regarding single vs bilateral lung transplant procedures and the need for cardiopulmonary bypass are often made based on pulmonary artery systolic pressures, we sought to examine the relationship between estimated and measured pulmonary artery systolic pressures using echocardiogram and catheterization, respectively. METHODS: We retrospectively reviewed all patients in our program who had measured pulmonary hypertension (n = 57). Patients with both echocardiogram-estimated and catheterization-measured pulmonary artery systolic pressures performed within 2 weeks of each other were included (n = 19). We analyzed results for correlation and linear regression in the entire group and in the patients with primary pulmonary hypertension (n = 8) and pulmonary fibrosis (n = 8). RESULTS: In patients with primary pulmonary hypertension, pulmonary artery systolic pressure was 94 +/- 27 and 95 +/- 15 mm Hg by echocardiogram and catheterization, respectively, with r(2) = 0.11; in patients with pulmonary fibrosis, 57 +/- 23 and 58 +/- 12 mm Hg with r(2) = 0.22; and in the whole group, 76 +/- 29 and 75 +/- 23 mm Hg with r(2) = 0.50. Thirty-two additional patients had mean pulmonary artery systolic pressure = 48 +/- 16 mm Hg by catheterization but either had no evidence of tricuspid regurgitation by echocardiogram (n = 22) or the pulmonary artery systolic pressure could not be measured (n = 10). CONCLUSIONS: In patients with pulmonary hypertension awaiting transplant, pulmonary artery systolic pressures estimated by echocardiogram correspond but do not serve as an accurate predictive model of pulmonary artery systolic pressures measured by catheterization. Technical limitations of the echocardiogram in this patient population often preclude estimating pulmonary artery systolic pressure.     

Post-transplant survival after lowering fixed pulmonary hypertension using left ventricular assist devices.

OBJECTIVE: We have previously shown that fixed pulmonary hypertension in cardiac transplant candidates can be lowered using left ventricular assist devices (LVADs). The post-transplant survival of these patients is uncertain as pulmonary hypertension may reappear, possibly affecting post-transplant survival. MATERIALS AND METHODS: Between 01/2000 and 01/2005 a total of 26 cardiac transplant candidates (92% male; mean age 56.2 years) in whom fixed pulmonary hypertension was lowered by LVAD implantation (pulmonary vascular resistance (PVR) before implantation: 5.1+/-2.8wood units (WU); PVR before cardiac transplantation: 2.0+/-.9WU) underwent cardiac transplantation at our institution. These patients were age and sex matched with 52 cardiac transplant candidates without pulmonary hypertension undergoing cardiac transplantation during the same time period. Study endpoints were peri-transplant complications and long-term survival. Mean follow-up was 36+/-14 months. RESULTS: Peri-transplant mortality was 5% in patients after LVAD therapy and 7% in patients without prior LVAD therapy (p=.089). We observed 2 cases (4%) of acute right heart failure requiring mechanical support in patients without prior LVAD therapy. None of the patients with LVAD therapy developed peri-transplant right heart failure requiring mechanical support. Incidence of other peri-transplant complications was comparable between the two groups. Log-rank (p=.124) revealed comparable long-term survival between patients with (1 year: 85%, 2 year: 85%, 3 year: 85%) and without (1 year: 90%, 2 year 82%, 3 year prior 79%) prior LVAD therapy. CONCLUSION: LVAD therapy lowers fixed pulmonary hypertension in cardiac transplant candidates with fixed pulmonary hypertension. Thereafter, long-term post-transplant survival is comparable to cardiac transplant recipients without pulmonary hypertension.     

Lung transplantation--10-year experience.

OBJECTIVE: The experience at our institution with various forms of lung transplantation (heart-lung, double lung and single lung) from December 1987 to September 1998 is reviewed and discussed. METHODS: During this decade, 282 procedures (46 heart-lungs (HLTx), 142 double lungs (DLTx) and 94 single lungs (SLTx)) have been performed in 258 patients (140 male, 118 female; age: 38 +/- 13 years). Major indications included pulmonary fibrosis (n = 73), obstructive lung disease (n = 55), cystic fibrosis (n = 48), primary pulmonary hypertension (n = 36), secondary pulmonary hypertension (majority Eisenmenger's syndrome) (n = 30), and retransplantation (n = 24). RESULTS: Early postoperative mortality (<90 days) was 13.9% (n = 36). The 1-, 3-, and 5-year survival rates in all recipients was 77, 70 and 63%, respectively. There was no significant difference in 1-year survival rates between the different procedures (HLTx: 78%, DLTx: 77%, SLTx: 77%). Significantly better 1-year survival was achieved in patients with cystic fibrosis (89%), pulmonary fibrosis (81%), obstructive lung disease (74%), and Eisenmenger's syndrome (83%) when compared to patients with primary pulmonary hypertension (55%). Survival rates remained unchanged during this period despite expanding indications during the last years. Causes of death in 90 recipients (HLTx: n = 19, DLTx: n = 37, SLTx: n = 34) included sepsis (n = 42), obliterative bronchiolitis (n = 28), cardiac failure (n = 5), and early allograft dysfunction (n = 2). Freedom from bronchiolitis obliterans syndrome (BOS) (>stage I ISHLT) was 80% at 1 year and 45% at 5 years. CONCLUSIONS: Lung transplantation offers a true therapeutic option with good early and midterm results. Yet, chronic graft dysfunction represents a major obstacle for long-term benefit of this procedure.     

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis

BackgroundLittle is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence.MethodsRetrospective study of individuals who had undergone a lung transplant (2000–2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records.ResultsThe cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24–35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period.ConclusionsThese findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.     

Rapid Resolution of Proteinuria of Native Kidney Origin Following Live Donor Renal Transplantation

To assess the contribution of the protein content of urine from the native kidneys to post-transplant proteinuria, we prospectively studied 14 live donor transplant recipients with a pre-transplant random urine protein to creatinine ratio (UPr:Cr) >0.5. Seven patients received preemptive transplants, and seven patients were on dialysis pre-transplant (with residual urine output). Resolution of proteinuria was defined as UPr:Cr < 0.2. Immunosuppression consisted of tacrolimus, mycophenolate mofetil and corticosteroids. Anti-hypertensive drugs that might reduce proteinuria were avoided during the study. The serum creatinine was 8.7 +/- 0.7 mg/dL pre-transplant, and the nadir post-transplant serum creatinine was 1.4 +/- 0.1 mg/dL. The pre-transplant UPr:Cr ranged between 0.5 and 9.2 (mean = 2.9 +/- 0.6). The UPr:Cr decreased to <0.2 in all 14 patients at a mean of 4.5 weeks post-transplant (range 1-10 weeks). In conclusion, in live donor renal transplant recipients with immediate graft function, proteinuria of native kidney origin resolves in the early post-transplant period. After the immediate post-transplant period, proteinuria cannot be attributed to the native kidneys, and work up for proteinuria should focus on the allograft.     

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.     

Influence of hypercholesterolemia on patient and graft survival in recipients of kidney transplants

AIM: The aim of this retrospective, single centre study, was to study the effect of pre- and post-transplant serum total cholesterol (TC) on patient and graft survival. We also sought to see whether patients who had very high TC (>8 mmol/L) had a higher incidence of graft failure and patient mortality compared with those whose cholesterol was only moderately elevated. METHODS: Records of 935 cadaver kidney transplants between 1984 and 1998 were examined. Patients were placed into three groups based on TC level: <5.5 mmol/L (group 1), 5.5-8 mmol/L (group 2) and >8 mmol/L (group 3). The mean TC value from the first five post-transplant years was taken to seek a correlation between TC and post-transplant events. RESULTS: The mean graft follow-up was 66.9 +/- 50.1 months, ranging from 0.1 to 191 months, while mean patient follow-up was 83.8 +/- 50.1 months, ranging from 0.5 to 191.6 months. Pre-transplant TC was available in 201 patients (21.5%), and post-transplant data was available (for first 5 yr) in 655 patients (70%). During the study period, 220 patients (23.5%) had died, 285 (30.5%) of the grafts had failed during the follow-up, while 129 (13.8%) of the patients died with a functioning graft. We found significantly longer survival of patients having a pre-transplant TC below 5.5 mmol/L vs. patients whose pre-transplant TC was above 5.6 mmol/L (p = 0.02). We also compared patients who had very high pre-transplant TC (>8 mmol/L) level with those whose TC was moderately elevated (5.5-8 mmol/L) and found that there was no higher incidence of graft failure (p = 0.77) nor patient mortality (p = 0.83). No difference could be found in graft survival based on pre-transplant TC. We also did not find a detrimental influence of post-transplant TC on the patient or graft survival. Diabetes mellitus (p = 0.006) and age over 50 yr (p = 0.007) affected patient survival, while low cyclosporine levels (p = 0.02) and acute rejection episodes (p = 0.009) affected graft survival. The mode of dialysis and time on dialysis prior to transplantation did not affect patient and graft survival. CONCLUSIONS: We found significantly greater survival of patients having a pre-transplant TC below 5.5 mmol/L. No difference could be found in graft survival based on pre-transplant TC. Post-transplant TC did not adversely affect patient or graft survival.     

Nasal polyposis in lung transplant recipients with cystic fibrosis

BackgroundChronic rhinosinusitis with nasal polyposis is common in patients with cystic fibrosis (CF). There are still many open questions regarding factors related to this condition. Furthermore, the prevalence of nasal polyposis and its implications for the outcomes in lung transplant recipients with cystic fibrosis are unknown.MethodsAll CF patients who underwent lung transplantation at our centre between November 1992 and December 2009 were included. Nasal polyp status was determined endoscopically at time sinus surgery and its relationships to gender, age at lung transplantation, Liou raw score, body mass index, FEV₁%predicted, diabetes mellitus, pre-transplant pseudomonas colonisation of the sinuses and the lungs, pre-transplant corticosteroid use and type of mutation of the CFTR gene were analysed. The post-transplant survival times and the incidence of bronchiolitis obliterans syndrome in patients with or without nasal polyposis were compared.ResultsNasal polyps were found in 19% (17 patients) of the 89 lung transplant recipients, whose data was available for statistical analysis. None of the factors analysed was related to the nasal polyp status. The post-transplant survival times and the incidence of bronchiolitis obliterans syndrome did not significantly differ between patients with or without nasal polyposis.ConclusionsCF-related nasal polyposis occurs in a relevant fraction of lung transplant recipients. A specific effect of nasal polyposis on post-transplant outcome could not be confirmed. Nevertheless, there was a trend to NP recurrence in patients with post‐transplant sinonasal pseudomonas colonisation and is a tendency of less chronic rejection in CF patients with nasal polyps.     

Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis

OBJECTIVE: Although lung transplantation is viewed as an acceptable option for patients with end-stage idiopathic pulmonary fibrosis, the survival benefit of this approach is still debated. This study examined whether there was a survival benefit of lung transplantation in a cohort of patients referred to our transplant center with a diagnosis of idiopathic pulmonary fibrosis according to American Thoracic Society criteria. METHODS: Forty-six patients accepted for lung transplantation during a 12-year period with a diagnosis of idiopathic pulmonary fibrosis form the basis of this study. Survival benefit offered by lung transplantation was assessed using Cox proportional-hazards modeling, with patients on a waiting list as the control group. RESULTS: Twenty-eight patients underwent lung transplantation (27 single and 1 double), 16 patients died while waiting, and 2 patients remained on the active waiting list. Diagnosis of idiopathic pulmonary fibrosis was made on histologic examination of the explanted lung or lung biopsy before lung transplantation. There was a pattern of usual interstitial pneumonia in 31 cases (67%). The 15 remaining patients fulfilled all American Thoracic Society criteria for idiopathic pulmonary fibrosis. The median waiting time for organs was 51 days. Survival after lung transplantation was 79.4% at 1 year, 63.5% at 2 years, and 39% at 5 years. The multivariable analysis showed that lung transplantation reduced the risk of death by 75% (95% confidence interval, 8%-86%; P =.03) after adjustment on potential confounding variables. CONCLUSIONS: Lung transplantation is effective in improving the survival of selected patients affected by idiopathic pulmonary fibrosis.     

Pre-transplant mechanical ventilation and outcome in patients with cystic fibrosis.

Mechanical ventilation for ventilatory failure has been considered a relative contraindication to subsequent lung transplantation. The purpose of this study was to test the hypothesis that patients with cystic fibrosis (CF) who are intubated and mechanically ventilated before transplantation have poorer post-transplant outcomes than do patients who are not ventilated.We compared the outcomes of 8 patients with CF who underwent mechanical ventilation for 62 +/-20 days (range, 3-153 days) before bilateral lung transplantation with outcomes of 24 patients with CF who did not undergo pre-transplant mechanical ventilation.Although time to extubation after transplantation was prolonged significantly (11 vs 4 days) for the pre-transplant ventilated group, days to hospital discharge, forced expiratory volume in 1 second (percent predicted) at 1 year after transplantation, and post-transplant survival as determined using the Kaplan-Meier method did not differ statistically between the 2 groups.Patients with CF who undergo pre-transplant endotracheal intubation and mechanical ventilation for respiratory failure have outcomes that do not differ significantly from those of patients with CF who do not require invasive ventilatory support before bilateral lung transplantation.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Outcomes of Lung Transplantation in Patients With Combined Pulmonary Fibrosis and Emphysema: A Single-Center Experience

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is a distinct clinical entity that can progress to end-stage lung disease. Patients with CPFE may develop pulmonary hypertension and face a predicted 1-year mortality of 60%. Lung transplantation is the only curative therapeutic option for CPFE. This report describes our experience after lung transplantation in patients with CPFE.MethodsThis retrospective, single-center study describes short- and long-term outcomes for adult patients who underwent lung transplant for CPFE.ResultsThe study included 19 patients with explant pathology-proven diagnosis of CPFE. The patients were transplanted between July 2005 and December 2018. Sixteen recipients (84%) had pulmonary hypertension before transplant. Of the 19 patients, 7 (37%) had primary graft dysfunction at 72 hours post-transplant. 1-, 3-, and 5-year freedom from bronchiolitis obliterans syndrome was 100%, 91% (95% CI, 75%–100%), and 82% (95% CI, 62%–100%), respectively. One-, 3-, and 5-year survival was 94% (95% CI, 84%–100%), 82% (95% CI, 65%–100%), and 74% (95% CI, 54%–100%), respectively.ConclusionOur experience demonstrates the safety and feasibility of lung transplant for patients with CPFE. Significant morbidity and mortality without lung transplant coupled with favorable post-transplant outcomes merit prioritization of CPFE in the Lung Allocation Score algorithm for lung transplant candidacy.     

Bronchogenic carcinoma complicating lung transplantation.

BACKGROUND: Malignancy is a well-recognized complication of solid-organ transplantation. Although a variety of malignancies have been reported in lung transplant recipients, a paucity of information exists regarding the incidence and clinical course of bronchogenic carcinoma in this patient population. METHODS: We conducted a retrospective cohort study of our lung transplant experience at the University of Pennsylvania. RESULTS: We identified 6 patients with bronchogenic carcinoma detected at the time of, or developing after, transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients with lung cancer had a history of smoking, with an average of 79 +/- 39 pack-years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had idiopathic pulmonary fibrosis. Lung cancers were all of non-small-cell histology and first developed in native lungs. Three patients had bronchogenic carcinoma at the time of surgery. The remaining 3 patients were diagnosed between 280 and 1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid course suggestive of an infectious process. The 1- and 2-year survival rates after diagnosis were 33% and 17%, respectively. CONCLUSION: Lung transplant recipients are at risk for harboring or developing bronchogenic carcinoma in their native lungs. Rapid progression to locally advanced or metastatic disease commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should be considered in the differential diagnosis of pleuroparenchymal processes involving the native lung.     

Lung and heart-lung transplantation. Evolution and new applications.

Heart-lung transplantation (HLT) and lung transplantation (LT) are effective treatment modalities for patients with advanced pulmonary parenchymal or vascular disease. Lung transplantation offers potential advantages over HLT, including reduced pretransplant waiting time and improved efficiency of organ utilization, and is currently being offered to patients formerly treated by HLT. To explore the relative merits of these procedures, the authors examined the results in 44 procedures (23 HLT and 21 LT) in 42 patients transplanted at their institution. Heart-lung transplant recipients included 20 adults and three children (ages 5,5 and 3). Most HLT patients had primary pulmonary hypertension (PPH) (n = 9) or Eisenmenger's syndrome (ES) (n = 8). Twenty-two of twenty-three patients have been long-term survivors (mean follow-up = 17.8 months, Kapaln-Meier survival at 12 months = 85%). Obliterative bronchiolitis (OB) has occurred in five patients (22%), and all have died. Of 21 LTs in 19 patients, nine had obstructive and eight had restrictive lung diseases. Three single-LT (SLT) patients had PPH, and one had ES secondary to a ventricular septal defect. Mean pulmonary artery pressures fell from 55 +/- 6 mm Hg before SLT to 21 +/- 3 mm Hg after SLT; p less than 0.001. Three pediatric patients (ages 4, 10, 17, and 17[re-transplant]) have undergone four SLTs. With mean follow-up of 6.4 months, LT patients have survival at 12 months of 80% (Kaplan-Meier). Lung transplant patients wait a far shorter time for their transplant than do HLT patients (166 vs. 384 days, p less than 0.03). Three patients (19%) have evidence of OB after SLT, with one death. By virtue of equal intermediate-term outcomes, shorter waiting times, and better use of donor organs in comparison with HLT, LT should be offered whenever possible to patients with end-stage pulmonary parenchymal or vascular disease. The authors' pediatric LT and HLT experience (7 treatments in 6 patients) is the largest reported to date and demonstrates the utility of these procedures in this group. Chronic rejection (OB) remains the greatest impediment to long-term survival in both LT and HLT pts.     

Interpreting Post-Transplant Proteinuria in Patients with Proteinuria Pre-Transplant

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.     

Lung transplantation for pulmonary vascular disease

BACKGROUND: Pulmonary hypertension (PHT) is a lethal condition resulting in markedly diminished life expectancy. Continuous prostaglandin I2 infusion has made an important contribution to symptom management, but it is not a panacea. Lung or heart-lung transplantation remains an important treatment option for end-stage PHT patients unresponsive to prostaglandin I2. This study reviews the outcomes after transplantation for PHT in our program. METHODS: A retrospective chart review was performed for 100 consecutive patients with either primary PHT (48%) or secondary PHT (52%) transplants since 1989. Living recipients were contacted to confirm health and functional status. RESULTS: Fifty-five adult and 45 pediatric patients underwent 51 bilateral lung transplants, 39 single lung transplants, and 10 heart-lung transplants. Mean age was 23.7 years (range, 1.2 months to 54.8 years) and mean pre-transplant New York Heart Association class was 3.2. Pre-transplant hemodynamics revealed a mean right atrial pressure of 9.6+/-5.4 mm Hg and mean pulmonary artery pressure of 64+/-14.4 mm Hg. Hospital mortality was 17% with early death predominantly because of graft failure and infection. With an average follow-up of 5.0 years, 1- and 5-year actuarial survival was 75% and 57%, respectively. Mean pulmonary artery pressure on follow-up catheterization was 22+/-6.0 mm Hg, and mean follow-up New York Heart Association class was 1.3 (p < 0.001 for both compared with pre-transplant). Diagnosis and type of transplant did not confer a significant difference in survival between groups. CONCLUSIONS: Whereas lung or heart-lung transplant for PHT is associated with higher early mortality than other pulmonary disease entities, it provides similar long-term outcomes with dramatic improvement in both quality of life and physiologic aspects.