Anti-skeletal muscle glycolipid antibodies in human heart transplantation as predictors of acute rejection: comparison with other risk factors

In forty-five patients who underwent orthotopic heart transplantation, the titer of anti-human skeletal muscle glycolipid antibodies (AGA) present in the sera at the moment of transplantation was correlated with the number of histologically diagnosed cellular grade 3A and humoral acute rejection episodes during the first 120 days after transplantation. Determination of a cutoff value of 0.800 for the AGA level was determined by a receiver operating characteristic curve. Thirteen of 19 patients (68.4%) with an AGA titer above 0.800 developed 24 severe rejection episodes, and of the 26 patients with an AGA titer below 0.800, only 4 (15.3%) presented 6 severe rejection episodes during that time. This was especially evident for the humoral rejection episodes, which were diagnosed in only 1 of the 26 patients with AGA below 0.800 and in 7 of the 19 with AGA above 0.800. Comparison by univariate analysis of other well-known risk factors for a greater number of rejection episodes during the early posttransplant period with the AGA level at the moment of transplantation revealed that the latter distinguished a greater number of patients at risk than the other factors, such as a female donor, the lymphocyte direct cross-match, or the status of the patients at transplantation; the odds ratios were 6.33 for the AGA level, 3.17 for the direct cross-match, and 2.76 for the status at transplantation. By multiple logistic regression analysis, the only relevant risk factors in our group of patients were the AGA level (P=0.0009) and the status at transplantation (P=0.0285). These results indicate that determination of the AGA level at the moment of transplantation could represent a useful method for distinguishing which patients are at risk for a greater number of rejection episodes during the early posttransplant period, with a greater sensitivity than other risk factors.     

Follicular fluid immunoreactive-inhibin concentrations in relation to follicular diameter and estradiol-17 beta, progesterone and testosterone concentrations in individual ovarian follicles in buffalo, Bubalus bubalis

BACKGROUND: Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation. METHODS: In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11]. RESULTS: During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS). CONCLUSIONS: Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.     

Effect of panel reactive antibody on live related donor kidney transplantation: Indian experience

Serum samples from 95 recipients, transplanted with kidneys from live related donors, were tested for the presence of panel reactive antibodies (PRA) in pre- and post-transplant serum samples by the extended microdroplet lymphocytotoxicity test. The immunoglobulin class of antibodies was tested by treatment of serum with dithiothreitol. A significant correlation was found between the high PRA found in the 75 pretransplant sera tested and the subsequent rejection episodes. In addition, the level of pretransplant PRA activity was associated with graft survival in that patients with low PRA had significantly superior graft survival than those with high PRA. Furthermore, the present data show that patients with historical high PRA, but current low PRA, had graft survival similar to that in recipients who had moderate PRA in their current sera. High PRA patients had more often a positive crossmatch than patients with low PRA. The PRA level was also associated with prolonged waiting period. Immunoglobulin class of antibodies was related to graft acceptance in that the presence of IgM antibodies was not detrimental to transplantation. The results in the present study suggest that PRA of < 10% is negligible, while more attention should be paid to patients with PRA > 10%.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

Pulmonary transplantation

OBJECTIVE: More than 2700 lung transplants have been performed since the initial clinical success in 1983. The evolution in the techniques of lung transplantation and patient management and the effects on results are reviewed. SUMMARY BACKGROUND DATA: Improvements in donor management, lung preservation, operative techniques, immunosuppression management, infection prophylaxis and treatment, rejection surveillance, and long-term follow-up have occurred in the decade following the first clinically successful lung transplant. A wider spectrum of diseases and patients treated with lung transplant have accentuated the shortage of suitable lung donors. The organ shortage has led to the use of marginal donors and a limited experience using living, related donors. METHODS: Changes in techniques and patient selection and management are reviewed and controversial issues and problems are highlighted. RESULTS: One-year survival of greater than 90% for single-lung transplant recipients and greater than 85% for bilateral lung transplant recipients have been achieved. Complications caused by airway complications has been reduced greatly. Obliterative bronchiolitis develops in 20% to 50% of long-term survivors and is the leading cause of morbidity and mortality after the first year after transplant. CONCLUSIONS: Lung transplantation has evolved into an effective therapy for a wide variety of causes of end-stage lung disease. Wider applicability requires solutions to the problems of donor shortage and development of obliterative bronchiolitis.     

Comparison of theory and experiment in pulsatile flow in cat lung

OBJECTIVE: A retrospective analysis was performed to examine the role of HLA antibodies and cytomegalovirus mismatch on the development of bronchiolitis obliterans syndrome and survival after lung transplantation. METHODS: Of 339 consecutive lung transplantations performed over a 102-month interval, 301 patients survived at least 3 months. There was a minimum follow-up period of 13 months. Bronchiolitis obliterans syndrome was defined as a decline in forced expiratory volume in 1 second less than 80% of posttransplantation baseline and/or histologic presence of obliterative bronchiolitis and was defined as occurring "early" if documented within 3 years of transplantation. Variables analyzed included preoperative donor and recipient cytomegalovirus status and the development of antibodies to human leukocyte antigens after transplantation. Microcytotoxicity was used to determine the presence of antibodies to human leukocyte antigens. Variables were subjected to Kaplan-Meier analysis to determine their impact on freedom from bronchiolitis obliterans syndrome and survival. RESULTS: The development of antibodies to human leukocyte antigens after transplantation correlated significantly with bronchiolitis obliterans syndrome (P = .02). The development of antibodies to human leukocyte antigens did not affect survival (P = .33) unless they were detected within 2 years of transplantation (P = .04). There was greater frequency of early bronchiolitis obliterans syndrome in cytomegalovirus seronegative patients who received allografts from seropositive donors compared with all other combinations (P = .02). There was also a trend toward worse survival of cytomegalovirus seronegative patients who received allografts from seropositive donors (P = .13). CONCLUSION: These data suggest that bronchiolitis obliterans syndrome is the result of an immune-mediated process in which HLA antibodies and cytomegalovirus may play a significant role.     

Pediatric and adult lung transplantation for cystic fibrosis

OBJECTIVE: This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. METHODS: Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. RESULTS: Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. CONCLUSION: Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.     

Prospective study of the value of transbronchial lung biopsy after lung transplantation

Transbronchial lung biopsy (TBB) has become the gold standard for the diagnosis of acute rejection and cytomegalovirus (CMV) pneumonia in lung transplant recipients. The aim of this study was to assess the value of regular surveillance TBB in stable asymptomatic patients and to establish the role of TBB as a follow-up procedure 1 month after a previous pathological biopsy result. We prospectively evaluated 76 TBBs performed in 17 lung transplant recipients. A definite pathological results was found in 14 of 15 TBBs performed for clinical indications: CMV pneumonia (5), acute rejection grade > or = A2 according to the criteria of the International Society for Heart and Lung Transplantation (ISHLT) (4), bronchiolitis obliterans (3), and desquamative interstitial pneumonitis (2). Fifteen of 45 surveillance TBBs performed in asymptomatic patients revealed significant abnormalities. Ten episodes of acute rejection ISHLT grade > or = A2 and three episodes of CMV pneumonia detected by TBB had direct therapeutic consequences. Nine of 16 follow-up TBBs performed 1 month after a pathological biopsy result again showed relevant pathological findings. With the exception of one severe haemorrhage, no life-threatening complications occurred. Our results suggest that transbronchial lung biopsies performed on a regular basis after lung transplantation are important for the detection of asymptomatic and/or persistent acute rejection or injection. In the long-term, this strategy might be the most effective tool in reducing the incidence of bronchiolitis obliterans, which is still the main obstacle for further improvement of long-term survival after lung transplantation.     

Lung transplantation in chronic airflow limitation

Lung transplantation is an option for appropriately selected patients with end-stage chronic airflow limitation. The functional results have been excellent after single or bilateral lung transplantation, and the medium-term survival results have been good. Obliterative bronchiolitis, however, thought to be a manifestation of chronic rejection, occurs in approximately 40% of recipients, and it is the major cause of late morbidity and mortality in lung transplant recipients.     

Pediatric lung transplantation. Indications, techniques, and early results

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.     

Obliterative bronchiolitis after lung and heart-lung transplantation

Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.     

Positive panel reactive antibody titers in patients bridged to transplantation with a mechanical assist device: risk factors and treatment

Patients who are bridged-to-transplantation with mechanical support have a high incidence of pretransplant sensitization defined by panel reactive antibody (PRA) titers greater than 10. Risk factors for positive PRA in patients with assist devices were investigated. From 1993 to 1997, 17 patients underwent implant surgery with CardioWest C-70 total artificial hearts (TAHs; CardioWest Technologies, Inc., Tucson, AZ), and 13 with Novacor left ventricular assist systems (LVASs; Baxter Healthcare, Novacor Division, Oakland, CA) for bridge-to-transplantation at this institution. Two patients died during implantation of the assist devices. Of the remaining 28 patients, four (14%) were women (3 with TAHs and 1 with an LVAS). All four women (100%) had a positive PRA, whereas only two of the 24 men (8%) had positive PRA (p < 0.0001). The transfusion histories of these patients were reviewed. Using chi-squared analysis (alpha = 0.05), the PRA levels were independent of transfusion of packed red blood cells and fresh frozen plasma. There was an association, however, between platelet transfusions and PRA levels. The times on device awaiting cardiac transplantation were also compared between the PRA positive and PRA negative groups. The average time to transplantation for PRA positive patients was 116 days, whereas the average waiting time for the PRA negative patients was 55 days (p = 0.05). Based on these data, a female patient with consistently positive PRA (93%) after TAH implantation underwent a transplant on post implant day 25 despite a positive lymphocytotoxic crossmatch with the donor. She was treated with plasmapheresis during cardiopulmonary bypass at the time of transplantation, and with four further treatments post transplant. As of this writing, she is alive and well on our standard triple immunotherapy. Therefore, women who are bridged-to-transplantation with assist devices are at risk for positive PRA. It is recommended that patients who are bridged-to-transplantation with assist devices and have high PRA levels be treated with perioperative plasmapheresis. With this aggressive approach, it may no longer be necessary to keep patients on mechanical support for prolonged periods, but possible to perform transplants as soon as suitable donors become available.     

Bronchiolitis obliterans syndrome: thin-section CT diagnosis of obstructive changes in infants and young children after lung transplantation

PURPOSE: To characterize the thin-section computed tomographic (CT) appearance of bronchiolitis fibrosa obliterans syndrome in infants and young children after lung transplantation. MATERIALS AND METHODS: Thin-section CT studies in six patients with bronchiolitis obliterans syndrome (age range, 2 months to 5 1/2 years) and in 15 control patients without obstructive airway disease (age range, 2 months to 7 years) who underwent bilateral lung transplantation were retrospectively reviewed. The thin-section CT scans were obtained during quiet sleep at a median of 24 months (range, 6-36 months) after transplantation. The CT studies were evaluated for mosaic perfusion, bronchial dilatation, bronchial wall thickening, and mucous plugging Final diagnoses in all patients were based pulmonary function test results. RESULTS: Thin-section CT findings in the six patients with clinically proved bronchiolitis obliterans syndrome were mosaic perfusion in five (83%) bronchial dilation in three (50%), and bronchial wall thickening in one (17%). Of the 15 control patients with normal pulmonary function test results, six (40%) had mosaic perfusion; none had bronchial dilatation or bronchial wall thickening. Mucous plugging was not seen in either group. Only the association of bronchial dilatation with bronchiolitis obliterans syndrome was significant (P = .02). CONCLUSION: Infants and young children with bronchiolitis obliterans syndrome after lung transplantation are more likely to have CT abnormalities than those with normal pulmonary function test results.     

Bronchiolitis obliterans syndrome in heart-lung transplantation: surveillance biopsies

Transbronchial biopsies (TBBs) are useful to diagnose acute rejection and infection in patients with lung transplants. The value of routine surveillance biopsies (S-TBBs) is not known, and such biopsies with a clinical indication are not without risk and are expensive. One hundred twenty-six 6-mo survivors of heart-lung transplantation (HLT) were studied to determine the effect of stopping S-TBBs on the development of bronchiolitis obliterans syndrome (BOS) and subsequent survival. Fifty-one received transplants while S-TBB was part of routine care (group A), and 75 received transplants after this practice was stopped (group B). There was no difference in patient characteristics. Group A had shorter graft ischemia (p < 0.01) and longer postoperative ventilation (p < 0.01). Maintenance immunosuppression was similar, but group A had more steroid pulses in the second 6 mo after HLT (p < 0.01). The number of patients free from any functional deterioration at 49 to 60 mo after HLT declined to 39% in group A and 64% in group B. The risk of developing BOS grade 1 in group A relative to group B was 1.63 (95% confidence intervals: 0.96-2.79, p = 0.07). Patient survival was similar in the two groups. A total of 86 TBBs were taken in the absence of any signs or symptoms and had low diagnostic yield. In summary, there was no increased incidence of BOS after stopping S-TBBs.     

Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)     

The lack of long-term detrimental effects on liver allografts caused by donor-specific anti-HLA antibodies

Recent reports indicate a higher incidence of both acute and chronic liver allograft rejection when, at the time of transplantation, the recipients serum contains donor-specific anti-HLA antibodies. From 9/89 to 5/91, 133 liver allografts were performed at our institution. Thirteen liver recipients had donor-specific IgG anti-HLA antibodies (complement-fixing) at the time of transplantation. In eleven patients, antibodies reacted to donor class I antigens while in 1 patient the donor-specific antibody had class II reactivity. Twelve patients have been followed for a minimum of 12 months (median 18 months, range 28-12 months). No hyperacute rejection was seen in any of the cases and four patients had acute rejections. Thus far only one of the twelve patients has biopsy evidence suggestive of chronic liver injury. The remaining have normal liver enzymes and bilirubin. Three of these twelve patients died (one from a myocardial infarction and the others from sepsis) accounting for a one-year graft survival of 75%. There was no significant statistical difference in the one-year graft survival in those recipients without donor-specific antibodies (i.e., 80.5%). In eight of the twelve patients, pretransplant preformed antibody level (PRA) was > 50%. In six of the thirteen patients donor-specific antibody was present at dilutions greater than 1:64. As previously reported, the donor-specific antibody disappeared from the serum posttransplant within hours and did not reappear. In vitro studies demonstrated no factor in portal or hepatic artery blood that could inhibit rabbit complement mediated lysis of anti-HLA antibodies. We conclude that it is not a contraindication to do liver transplants in the presence of donor-specific anti-HLA antibodies.     

Infections in patients with cystic fibrosis following lung transplantation

BACKGROUND: There is controversy over whether colonization with drug-resistant organisms is a contraindication to lung transplantation. METHODS: We undertook a retrospective review of the results of lung transplantation for patients with cystic fibrosis (CF) at Duke University Medical Center. RESULTS: As of May 1996, 21 patients with CF underwent bilateral lung transplantation. The first patient died within 24 h of transplantation from sepsis due to Stenotrophomonas maltophilia. Of the remaining 20 patients, 17 (85%) are alive and in stable condition. The three deaths were related primarily to bronchiolitis obliterans at 4 and 18 months in two patients and to cytomegalovirus pneumonitis at 5 months in the other patient. The 17 surviving patients have been followed up for a mean of 13 months (range, 0.5 to 34 months). Most of them were colonized and infected with multidrug-resistant organisms before transplantation. Following transplantation, 11 patients had complications from infections. One patient had bacteremia due to a panresistant Burkholderia cepacia and was treated successfully. Two patients had bacteremia and wound infection due to Burkholderia gladioli, previously thought to be pathogenic only in plants. Both patients were treated successfully. Of the six patients with Aspergillus fumigatus isolated from cultures before transplantation, only one had invasive disease following transplantation and responded to treatment. CONCLUSION: The organisms present before transplantation were not the primary cause of mortality in our patient population. Our findings suggest that lung transplantation should be considered in CF patients infected with multidrug-resistant organisms.     

Humoral (antibody-mediated) rejection in lung transplantation

To confirm the existence and characterize the pathologic features of humoral (antibody-mediated) lung rejection, we prospectively studied 55 lung transplant recipients (24 male [44%] and 31 female [56%], age range 14 to 69 years [mean 45]). The time between transplantation and biopsy ranged from 2 to 1546 days (mean 274). We performed direct immunofluorescence with C3, immunoglobulin M, and immunoglobulin G antibodies on frozen sections of 106 transbronchial biopsies and one wedge biopsy and compared the results with 13 explanted lungs, one donor lung, and two controls. The histologic diagnoses of these 107 biopsies included acute cellular rejection (62, 58% [minimal 23, mild 33, moderate 5, and severe 1]), chronic rejection (eight, 7%), chronic vascular rejection (two, 2%), acute vasculitis (five, 5%), cytomegalovirus pneumonitis (two, 2%), acute pneumonia (two, 2%), acute organizing pneumonia (two, 2%), diffuse alveolar damage (one, 1%), no evidence of rejection or infection (30, 28%), lipoid pneumonia (one, 1%), and inadequate for histologic diagnosis (one, 1%). Eighty-nine of 106 (84%) transbronchial biopsies, the wedge biopsy, and control lungs were satisfactory for direct immunofluorescence, because each contained alveolate lung parenchyma and arterioles or venules. There was no demonstrable immunofluorescence in the wall of the blood vessels or in the lung parenchyma in any case. We conclude that (1) transbronchial biopsies and wedge biopsies provide adequate material to evaluate humoral rejection, and (2) in spite of the large population studied, the satisfactory material obtained, and the wide range of histologic diagnoses, we could not demonstrate the occurrence of humoral rejection in the lung.     

Mononuclear phagocyte populations in the transplanted human lung

BACKGROUND: Dendritic cells (DC) are essential for the development of alloreactivity, however, little has been published regarding the distribution and phenotype of these and related mononuclear cells in human lung transplantation. METHODS: Lung frozen sections were examined for the presence of CD1a+ DC and for mononuclear cells and alveolar macrophages expressing CD11b and CD68. The effects of transplantation and immunosuppression were assessed by comparison of normal transplant transbronchial biopsy specimens to specimens from unused donor lungs; the normal transbronchial biopsy specimens also were compared with those showing rejection or obliterative bronchiolitis. RESULTS: All biopsy specimens, including those with obliterative bronchiolitis, showed a marked depletion of CD1a+ DC in lung allografts. This has not been described previously. In addition, transplantation and immunosuppression reduced alveolar macrophage coexpression of CD68 and CD11b, and this was reversed in acute rejection. CONCLUSION: The roles of pulmonary DC and other mononuclear phagocyte subpopulations need to be further defined, and data from animal models of lung transplantation should be interpreted with caution.     

Altered binding of the NF-GMa transcription factor is involved in the upregulated production of TNF-alpha by macrophages of mammary tumor bearing mice

BACKGROUND: Despite improving results in lung transplantation, a significant number of grafts fail early or late postoperatively. The pulmonary retransplant registry was founded in 1991 to determine the predictors of outcome after retransplantation. We hypothesized that ambulatory status of the recipient and center retransplant volume, which had been previously shown to predict survival after retransplantation, would also be associated with improved graft function postoperatively. METHODS: Two hundred thirty patients underwent retransplantation in 47 centers from 1985 to 1996. Logistic regression methods were used to determine variables associated with, and predictive of, survival and lung function after retransplantation. RESULTS: Kaplan-Meier survival was 47% +/- 3%, 40% +/- 3%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the predictors of survival included ambulatory status or lack of ventilator support preoperatively (p = 0.005; odds ratio, 1.62; 95% confidence interval, 1.15 to 2.27), followed by retransplantation after 1991 (p = 0.048; odds ratio, 1.41; 95% confidence interval, 1.003 to 1.99). Ambulatory, nonventilated patients undergoing retransplantation after 1991 had a 1-year survival of 64% +/- 5% versus 33% +/- 4% for nonambulatory, ventilated recipients. Eighty-one percent, 70%, 62%, and 56% of survivors were free of bronchiolitis obliterans syndrome at 1, 2, 3, and 4 years after retransplantation, respectively. Factors associated with freedom from stage 3 (severe) bronchiolitis obliterans syndrome at 2 years after retransplantation included an interval between transplants greater than 2 years (p = 0.01), the lack of ventilatory support before retransplantation (p = 0.03), increasing retransplant experience within each center (fifth and higher retransplant patient, p = 0.04), and total center volume of five or more retransplant operations (p = 0.05). CONCLUSIONS: Nonambulatory, ventilated patients should not be considered for retransplantation with the same priority as other candidates. The best intermediate-term functional results occurred in more experienced centers, in nonventilated patients, and in patients undergoing retransplantation more than 2 years after their first transplant. In view of the scarcity of lung donors, patient selection for retransplantation should remain strict and should be guided by the outcome data reviewed in this article.