Early colonization with pseudomonas in cystic fibrosis (CF) lung transplant recipients is associated with poor long-term survival

The Journal of Heart and Lung Transplantation Volume 21, Number 1 thromboembolic cerebrovascular events was significantly lower in group II (6%) than in group I (20%), p ⫽ 0.018. The incidence of bleeding was mildly increased in group I. Pocket infections occurred in 24% in group I vs 11% in group II, p ⫽ 0.010. Only one patient (5%) in group II died while on the device, vs 9 (36%) in group II, p ⫽ 0.009. Conclusion: Our results proved that preperitoneal implantation, use of a new generation of vascular grafts, extensive drainage and a more restricted anticoagulation regimen result in better outcome following LVAS treatment for advanced heart failure. 144 OUTCOME OF MINIMAL ACUTE REJECTION (GRADE A1) IN LUNG TRANSPLANT RECIPIENTS: THE NEED FOR CAREFUL OBSERVATION P.M. Hopkins, C.L. Aboyoun, P.N. Chhajed, M.L. Plit, S.P. Rainer, M.A. Malouf, A.R. Glanville, The Lung Transplant Unit, St. Vincent’s Hospital, Sydney, Australia The clinical significance of minimal acute rejection (AR), ISHLT grade A1, on transbronchial lung biopsy (TBB) in surveillance protocols is unknown. Current evidence suggests that asymptomatic A1 lesions progress infrequently and have no association with subsequent development of obliterative bronchiolitis (OB). Aim: To describe the occurrence and outcome of A1 TBB in our lung transplant (LT) population. Methods: Prospective analysis of 1329 TBB performed in LT recipients between January 1995 to December 2000. Surveillance biopsy was performed at 3,6 weeks, 3,4,6 months post transplant and diagnostic biopsy in symptomatic patients. Patients with A1 rejection on surveillance TBB did not receive a steroid pulse. Results: The patient population n⫽245 (M:F,120:125) included 38 heart-lung, 76 single and 131 bilateral LT recipients of mean age 39.4 ⫾13.3 years. 299 of 1329 TBB (22%) in 143 (58%) study participants confirmed A1 histology at a mean postoperative day (POD) of 263 ⫾353 (range 11-2045). 78 of 245 patients (32%) experienced multiple (ⱖ2) A1 TBB in the first 12 months post transplant. 33(11%) A1 biopsies were symptomatic and received a steroid pulse, with only 2 cases progressing to ⱖA2 rejection at 3 months follow-up. 64 of 266 surveillance A1 biopsies (24%) proceeded to AR at follow up with new lymphocytic bronchiolitis (LB) developing in 40 cases. 44(14.7%) of initial A1 lesions had associated LB that persisted in 19 cases at follow up. Progression to AR was significantly (p⬍0.05) reduced by administration of steroids and not associated with initial B grade inflammation. OB developed in 68% of patients with multiple A1 TBB at a mean POD of 599 ⫾435, compared to 43% of patients with ⱕ1 A1 lesion at a mean of 819 ⫾526 (t test; p⫽0.0146). The survival of each group on logrank Kaplan-Meier analysis was not significantly different (p⫽0.1196). Conclusions: Asymptomatic grade A1 rejection has a moderate risk of progressing to acute rejection within 3 months. Patients who experience multiple A1 lesions in the first 12 months post transplant develop earlier onset obliterative bronchiolitis and may warrant augmented immunosuppression. 145 LYMPHOCYTIC BRONCHIOLITIS ON TRANSBRONCHIAL LUNG BIOPSY IN LUNG TRANSPLANT RECIPIENTS- THE PERSISTING NEMESIS

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C.L. Aboyoun, P.M.A. Hopkins, P.N. Chhajed, M.L. Plit, S.P. Rainer, M.A. Malouf, A.R. Glanville, The Lung Transplant Unit, St. Vincent’s Hospital, Sydney, Australia Background: Lymphocytic bronchiolitis (LB) on transbronchial lung biopsy (TBB) has been linked to the ultimate development of bronchiolitis obliterans syndrome (BOS) but the short-term outcome is unknown. Aim: To describe the epidemiology and outcome of LB (ISHLTⱖB2) in our lung transplant (LT) patient population. Methods: Analysis of 1329 TBB in 245 LT recipients between January 1995 to December 2000 was undertaken. Surveillance TBB was performed at 3,6,9 weeks and 3,6 months, with diagnostic biopsy in symptomatic patients. Steroids were routinely administered for ⱖB2 grade inflammation. Results: The patient population n⫽245 (M:F⫽120:125) consisted of 38 heart-lung, 76 single lung, and 131 bilateral lung transplant recipients of mean age 39⫾13 (range 12-62). 37% TBB were performed within 6 months post LT with 68% as surveillance. 309/1329(23%) TBB in 150(61%) patients showed LB at a mean postoperative day of 408⫾534 (range 8-2383). Active airway inflammation on TBB was mild (B2) in 191(14%), moderate (B3) in 116(9%), and severe (B4) in 2(0.15%). 122/309(39%) TBB with ⱖB2 had associated rejection ⱖA2. 73(30%) patients had multiple ⱖB2 grade lesions in the first 12 months post transplant. New ⱖA2 rejection at 3-month follow up was seen in 8(4%) TBB whilst 100(53%) had persistent ⱖB2 grade inflammation. 46/75(63%) of patients with multiple ⱖB2 lesions developed BOS at a mean POD of 700⫾430 (range 141-2201) compared with 41/75(55%) with a single ⱖB2 lesion at 873⫾506 (range 132-1892) (p⫽0.025). Survival of each group using Kaplan-Meier analysis was equivalent. Conclusion: Our data show LB is often refractory to steroid therapy, and demonstrate for the first time that multiple ⱖB2 lesions in the first 12 months post LT are a risk factor for early onset BOS. 146 EARLY COLONIZATION WITH PSEUDOMONAS IN CYSTIC FIBROSIS (CF) LUNG TRANSPLANT RECIPIENTS IS ASSOCIATED WITH POOR LONG-TERM SURVIVAL M.P. Steele, R.D. Davis, R.H. Messier, R. Pietrobon, B.D. Alexander, J.B. Rea, K.G. Setliff, S.M. Palmer, Duke University Medical Center, Durham, NC Background: The causes and risk factors for late death after lung transplantation are not well understood, but most late deaths are thought to be related to infection and the development of chronic rejection manifest as bronchiolitis obliterans syndrome (BOS). After transplant, some but not all, CF patients become colonized with Pseudomonas species. The relationship between early posttransplant infection with Pseudomonas and long term patient survival is unknown. Methods: We retrospectively reviewed medical records from the first 74 consecutive CF patients who underwent bilateral lung transplant at Duke and extracted data pretransplant, perioperative, and posttransplant clinical and microbiological data. Patients with ⬍ 1 yr. follow-up (14 patients), ⬍ 30 day survival (3 patients), and B. cepacia pretransplant (10 patients) were excluded from subsequent analysis. Early colonization is defined as patients having a positive bronchoalveolar lavage (BAL) culture for Pseudomonas within six months posttransplant.

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Results: 47 patients were included in the analysis, and by six months posttransplant, 23 (40%) had a positive BAL culture for Pseudomonas. In Kaplan-Meier analysis, early colonization with Pseudomonas is associated with decreased survival (p⫽0.027, by log-rank test), and a fourfold increase risk of death (hazard ratio⫽ 4.09, 95% CI 1.05,15.8, by Cox proportional hazards test). Other predictors of survival were donor age ⬍ 30 yr. old (p⫽0.04), and more than 2 episodes of acute rejection (p⫽0.003). Conclusion: Early colonization or infection with Pseudomonas aeruginosa in CF lung transplant recipients is associated with significantly worse long-term survival. Additional research is needed to define the risk factors for early posttransplant infection, mechanisms of colonization in the donor lungs, and independent contribution of colonization to late death through multivariate analyses. 147 ANTI-REFLUX SURGERY IMPROVES PULMONARY FUNCTION IN LUNG TRANSPLANT PATIENTS C.L. Lau, S.M. Palmer, D. Hadjiliadis, T.N. Pappas, W.S. Eubanks, R.D. Davis, Duke Lung Transplant Program, Duke University Medical Center, Durham, NC Background: As immediate posttransplant surgical outcomes have improved the greatest limitation of lung transplantation remains chronic allograft dysfunction. While immunologic factors are believed to be the primary cause of chronic allograft dysfunction other injuries to the lung may also play a role. Gastroesophageal reflux disease (GERD) with resultant aspiration has been implicated as a potential contributing factor in chronic allograft dysfunction. Surgical treatment of GERD has been shown to be safe with minimal morbidity in the lung transplant population. In this study we sought to determine the effect of fundoplication surgery in lung transplant patients with documented GERD. Methods: Thirty-four of the 380 lung transplants performed at Duke University Medical Center underwent anti-reflux surgery for documented GERD. Their pulmonary function and BOS level was assessed pre and post anti-reflux surgery. To be included patients had to be at least 6 months post fundoplication. Results: Twenty-one of the 34 lung transplants were bilateral and 13 were single. Thirteen of the 34 transplants were for COPD, 12 were for CF, 3 were for IPF, and 6 were for other diagnoses. The anti-reflux surgeries included 29 laparoscopic nissen fundoplications, 4 laparoscopic toupees, and one open nissen (converted secondary to extensive adhesions). Twenty four of the thirty four patients were at least six months from their anti-reflux operation. Prior to anti-reflux surgery average FEV1 was 1.8 L/min, post anti-reflux surgery average FEV1 increased to 2.2 L/min (p⬍0.00002). At the time of fundoplication the patients were in the following BOS categories: BOS 0, 13 patients; BOS 1, 11 patients; BOS 2, 6 patients; and BOS 3, 4 patients. Those patients with less severe BOS prior to anti-reflux surgery experienced a more marked improvement in their pulmonary function. Of the eleven patients with BOS 1 prior to fundoplication, 6 became BOS 0 post fundoplication. Conclusions: Anti-reflux surgery may prevent the decline and even at least temporarily improve the pulmonary function of lung transplant patients with chronic aspiration secondary to GERD. The best time to perform anti-reflux surgery remains to be determined.

The Journal of Heart and Lung Transplantation January 2002 148 PRE-TRANSPLANT PRA IN LUNG TRANSPLANT RECIPIENTS IS ASSOCIATED WITH SIGNIFICANTLY WORSE POST-TRANSPLANT SURVIVAL IN A MULTICENTER STUDY D. Hadjiliadis,1 G. Carlos,1 C. Chapparo,1 N.L. Reinsmoen,2 L.G. Singer,1 M.P. Steele,3 T.K. Waddell,1 R.D. Davis,4 M. Hutcheon,1 S.M. Palmer,3 S. Kashavjee,1 1Toronto Lung Transplant Program, University of Toronto, Toronto, Ontario, Canada; 2Pathology, Duke University, Durham, NC; 3Pulmonary/ Critical Care, Duke University, Durham, NC; 4Thoracic Surgery, Duke University, Durham, NC Purpose: The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction. Methods: A retrospective study of all first lung transplant recipients from the University of Toronto (1/83-7/01, n⫽380) and Duke University (4/92-6/00, n⫽276) was performed. Demographic data, survival information and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the KaplanMeier method, and groups were compared with the Wilcoxon test. Logistic regression of survival at 2-years was used for multivariable analysis. Results: 101/656 (15.4%) recipients had a PRA greater than zero, 37/656 (5.6%) had a PRA greater than 10% and 20/656 (3.0%) had a PRA higher than 25%. Patients with PRA greater than 25% had decreased median survival compared to the rest of the patients (1.5 vs. 5.2 years). The group with PRA greater than 25% had worse survival than the group with PRA less than 25% at 1-month (70% vs. 90%), 1-year (65% vs. 76%), and 5-years (31% vs. 50%), respectively (p⬍0.001, Wilcoxon test). This effect remained significant after multivariable analysis that included center, type of transplant, recipient age and gender. Discussion: Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments like plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated. 149 OUTCOME FOLLOWING SIMULTANEOUS AND SEQUENTIAL LUNG-LIVER TRANSPLANTATION: ANALYSIS OF THE ISHLT/UNOS JOINT THORACIC REGISTRY S. Fischer,1 L.E. Bennett,2 M. Strueber,1 T.K. Waddell,3 J. Niedermeier,1 S. Keshavjee,3 A. Haverich,1 1Hannover Thoracic Organ Transplant Program, Hannover Medical School, Hannover, Germany; 2UNOS, Richmond, VA; 3Toronto Lung Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada The combined transplantation (Tx) of the lung and the liver is a rare indication for patients with end stage lung and liver disease, but the outcome has not been analysed yet. We analysed the ISHLT/UNOS Joint Thoracic Registry to determine the outcome and predictors of survival. There were 54 lung-liver transplants