Use of taurolidine in lung transplantation for cystic fibrosis and impact on bacterial colonization.

OBJECTIVES: The presence of bacterial colonization that causes chronic pulmonary infections in cystic fibrosis (CF) patients remains a key issue before lung transplantation. We sought to assess the impact of intraoperative taurolidine lavage on bacterial colonization and long-term outcomes following lung transplantation in CF patients. METHODS: Between 2007 and 2013, 114 CF patients underwent lung transplantation at our institute, and taurolidine 2% bronchial lavage was applied in a substantial proportion of patients (n = 42). A detailed analysis of donor and recipient bacterial colonization status in treatment and control groups and their impact on outcome was performed. RESULTS: The proportion of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine group at 3 months (P < 0.001) and at 1 year (P = 0.053) postoperatively, despite no differences before transplant (P = 1.000). Moreover, a complete eradication of Burkholderia cepacia and Stenotrophomonas maltophilias colonizations could be achieved in the taurolidine group, whereas in the non-taurolidine group, persistent B. cepacia and S. maltophilias colonizations were observed. Early outcome in the taurolidine group was superior regarding fraction of expired volume in 1 s at 3 and 6 months after surgery with 74.5 ± 14.6 vs 60.4 ± 17.5 (P < 0.001) and 80.6 ± 16.9 vs 67.2 ± 19.4 (P = 0.005) percent of predicted values, respectively. In terms of long-term overall survival (P = 0.277) and freedom from bronchiolitis obliterans syndrome (P = 0.979), both groups were comparable. CONCLUSIONS: Taurolidine might be associated with a reduced proportion of CF patients colonized with multiresistant pathogens, particularly with P. aeruginosa. Long-term results should be further assessed in larger multicentre trials.

Escalation of extracorporeal life support as a bridge to lung transplantation in end-stage lung disease.

Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTx) is not uncommon, but it is not commonplace yet. We present a case of a 45-year-old man with cystic fibrosis with recent deterioration in lung function who was initially supported with veno-venous (VV) ECMO. However, he subsequently required conversion to veno-veno-arterial (VVA) ECMO. After 21 days of support, he underwent double lung transplantation, with an uneventful postoperative course. This case shows that, in patients with end-stage respiratory failure awaiting lung transplantation, extracorporeal life support may require escalation to improve gas exchange and address circulatory requirements.

Influence of history of cannabis smoking in selected donors on the outcomes of lung transplantation.

OBJECTIVES: Cannabis is the most commonly abused illicit drug and the smokers are at the risk of lung infections, bullous emphysema and lung cancer. However, no evidence about the outcomes of lung transplantation (LTx) utilizing the lungs from such donors is available in the literature. METHODS: We retrospectively analysed lung 'organ offers' and LTx at our centre between January 2007 and November 2013. The outcomes of LTx utilizing lungs from donors with a history of cannabis smoking were compared with the outcomes of those with no such history using unadjusted model as well as propensity score matching. RESULTS: A total of 302 LTxs were performed during this period and were grouped depending on the history of cannabis smoking in donors-'cannabis' (n = 19) and control group (n = 283). All the donors in 'cannabis' group were tobacco smokers compared with 43% in the control group. Preoperative characteristics in recipients in both groups were comparable. Intraoperative and post-LTx variables including 1- and 3-year survivals were comparable in both groups. CONCLUSIONS: The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after LTx and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.

Zonal organ allocation system and its impact on long-term outcomes after lung transplantation: a propensity score matched analysis†.

OBJECTIVE: Zonal organ allocation system comprises organ procurement by teams within a specific geographical area of each retrieval team. Therefore, in a substantial number of cases organs are retrieved by 'foreign' teams and are sent for transplantation to the implanting centre. The aim of this study was to assess the impact of zonal organ allocation system on early- and long-term outcomes after lung transplantation (LTx). METHODS: Included were 331 consecutive patients who underwent LTx performed at Harefield Hospital between January 2007 and January 2015. Recipients were divided into two groups depending on the organ retrieval team: 204 (61.6%) patients were transplanted using lungs procured by our institutional team (institutional group), whereas 127 (38.4%) organs were retrieved by other teams (external group) from experienced transplant centres in the UK. To exclude selection bias and other confounders, a 1:1 propensity score-based matching procedure was performed resulting in a total number of 238 donors and recipients who were well matched for baseline characteristics. The primary end-points were overall survival after LTx and freedom from bronchiolitis obliterans syndrome (BOS). Secondary end-points were perioperative clinical characteristics as well as adverse events that occurred over the follow-up. RESULT: After propensity score matching all donor characteristics and all baseline recipient characteristics were statistically similar between the two groups. In terms of early postoperative results, both groups were statistically comparable. However, there was a trend towards higher incidence of primary graft dysfunction in the external group (P = 0.054). Regarding long-term results with up to 7 years of follow-up, the overall survival also appeared to be poorer in the external group; however, this difference did not reach statistical significance. The freedom from BOS over the long-term follow was significantly poorer in the external group (P = 0.040). CONCLUSION: Despite excellent early outcomes the zonal allocation system might be associated with significantly poorer long-term outcomes in terms of freedom from BOS after bilateral LTx. Further research is needed to find the underlying factors leading to these results.

Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system.

INTRODUCTION: Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation.

BACKGROUND Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. MATERIAL AND METHODS Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. RESULTS Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. CONCLUSIONS Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies.

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.

RATIONALE: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. MEASUREMENTS AND MAIN RESULTS: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape. CONCLUSIONS: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

OBJECTIVES: Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. METHODS: Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. RESULTS: There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. CONCLUSIONS: Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further larger prospective trials are warranted to confirm our preliminary results and to elaborate long-term outcomes.

Extended Recipient Criteria in Lung Transplantation: Impact of Pleural Abnormalities on Primary Graft Dysfunction.

BACKGROUND: Because of improved surgical expertise and intraoperative management, pleural disease (PD+) represents a relatively minor contraindication to lung transplantation (LTx). The presence of pleural abnormalities from previous procedures or pleural involvement from fungal or bacterial disease is not considered a limiting factor for LTx. However there are no studies available to assess the impact of pleural diseases on short- and midterm outcomes after LTx. METHODS: We retrospectively reviewed 163 consecutive patients who underwent LTx between 2010 and 2013. Patients were divided according to the presence of pleural abnormalities before the operation (PD+ versus PD-). The primary end point of the study was primary graft dysfunction (PGD; grade 3) and overall survival. To avoid possible selection bias and to heck the robustness of the results, a propensity score-matching analysis (1:3) was performed. RESULTS: A total of 26 patients (16%) had pleural abnormalities before transplantation. Intra- and postoperative variables were comparable. PD+ was associated with a significantly higher incidence of PGD at 0 and 48 hours postoperatively (p = 0.037 and p = 0.032, respectively). Moreover, PD+ was associated with significantly worse survival at 3 months (p = 0.021). Although there was a trend toward worse early overall survival in the Kaplan-Meier estimate (Breslow p = 0.050), midterm survival was comparable (log-rank p = 0.240). CONCLUSIONS: LTx in patients with preoperative pleural abnormalities is feasible. Identifying higher-risk recipients with pleural abnormalities might have important clinical relevance because of a higher incidence of PGD and worse early survival, even though midterm survival is comparable.

Outcomes of minimally invasive lung transplantation in a single centre: the routine approach for the future or do we still need clamshell incision?

OBJECTIVES: Minimally invasive lung transplantation (MILT) via bilateral anterior thoracotomies has emerged as a novel surgical strategy with potential patient benefits when compared with transverse thoracosternotomy (clamshell incision, CS). The aim of this study is to compare MILT with CS by focusing on operative characteristics, postoperative organ function and support and mid-term clinical outcomes at Harefield Hospital. METHODS: It was a retrospective observational study evaluating all bilateral sequential lung transplants between April 2010 and November 2013. RESULTS: CS was performed in 124 patients and MILT in 70 patients. Skin-to-skin surgical time was less in the MILT group [285 (265, 339) min] compared with CS [380 (306, 565) min] and MILT-cardiopulmonary bypass [426 (360, 478) min]. Ischaemic time was significantly longer (502 ± 116 vs 395 ± 145 min) in the MILT group compared with CS (P < 0.01). Early postoperative physiological variables were similar between groups. Patients in the MILT group required less blood [2 (0, 4) vs 3 (1, 5) units, P = 0.16] and platelet transfusion [0 (0, 1) vs 1 (0, 2) units, P < 0.01]. The median duration of mechanical ventilation was shorter (26 vs 44 h, P < 0.01) and intensive therapy unit stay was 2 days shorter (5 vs 7) in the MILT group. While overall survival was similar, fraction of expired volume in 1 s (FEV1) and forced vital capacity (FVC) were consistently higher in the MILT group compared with CS during mid-term follow-up after transplantation. Specifically, FEV1 and FVC were, respectively, 86 ± 21 and 88 ± 18% predicted in the MILT group compared with 74 ± 21 and 74 ± 19% predicted in the CS group (P < 0.01) at the 6-month follow-up. CONCLUSIONS: MILT was successfully introduced at our centre as a novel operative strategy. Despite longer ischaemic times and a more complex operation and management, MILT appears to offer early postoperative and mid-term clinical benefits compared with our traditional approach of clamshell operations. These observations warrant larger definite studies to further evaluate the impact of MILT on physiological, clinical and patient-reported outcomes.

Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

GORD symptoms in lung transplantation: how efficient is the reflux symptom index questionnaire compared to the esophageal impedance test?

OBJECTIVE: As Gastroesophageal reflux disease (GORD) affects long-term survival in lung transplant recipients, the aim of this observational prospective study was to analyze the efficacy of The Reflux Symptom Index Questionnaire (RSI) compared to the esophageal impedance test. METHODS: Both esophageal impedance studies and RSI questionnaire were routinely performed in all patients who had completed rehabilitation following lung transplantation from June 2013 till March 2014. RSI generates a score of between zero and forty-five, taking into account any symptoms within four wk of the questionnaire. Our analysis considered RSI score cut-offs of 10 and 13 indicating significance of reflux. RESULTS: Out of 84 patients, 50 (59.5%) had evidence of GORD detected by impedance studies, whereas only 33 (39.2%) and 22 (26.2%) had RSI >10 and 13, respectively. An elevated RSI was not found to be associated with positive impedance studies using a score of either 10 or 13 (p = 0.127 and p = 0.142, respectively); 32.1% (n = 27) and 40.5% (n = 34) were found to have negative RSI and positive impedance test using 10 or 13 as cut-off, respectively. CONCLUSION: RSI Score is an unreliable predictor of GORD among lung transplant recipients. The authors therefore recommend the routine use of impedance testing in post-transplant patients.

The role of cardiopulmonary bypass in lung transplantation.

BACKGROUND: The risk-benefit for utilizing cardio-pulmonary bypass (CPB) in lung transplantation (LTx) remains debatable. This study compares outcomes after LTx utilizing different CPB strategies - elective CPB vs. off-pump vs. off-pump with unplanned conversion to CPB. METHODS: A total of 302 LTx performed over seven yr were divided into three groups: "off-pump" group (n = 86), "elective on-pump" group (n = 162), and "conversion" group (n = 54). The preoperative donor and recipient demographics and baseline characteristics and the postoperative outcomes were analyzed; 1:1 propensity score matching was used to identify patients operated upon using elective CPB who had risk profiles similar to those operated upon off-pump (propensity-matching 1) as well as those emergently converted from off-pump to CPB (propensity-matching 2). RESULTS: Preoperative group demographic characteristics were comparable; however, the "off-pump" patient group was significantly older. The "conversion" group had a significantly greater number of patients with primary pulmonary hypertension, pulmonary fibrosis, preoperative mechanical ventilation, and preoperative extracorporeal life support (ECLS). Postoperatively, patients from the "conversion" group had significantly poorer PaO2 /FiO2 ratios upon arrival in intensive care unit (ICU) and at 24, 48, and 72 h postoperatively, and they required more prolonged ventilation, longer ICU admission, and they experienced an increased need for ECLS than the other groups. Overall, cumulative survival at one, two, and three yr was significantly worse in patients from the "conversion" group compared to the "off-pump" and "elective on-pump" groups - 61.9% vs. 94.4% vs. 86.9%, 54.4% vs. 90.6% vs. 79.5% and 39.8% vs. 78.1% vs. 74.3%, respectively (p < 0.001). The "off-pump" group had significantly better PaO2 /FiO2 ratios, and a significantly shorter duration of ventilation, ICU stay, and hospital length of stay when compared to the propensity-matched "elective on-pump" group. There were no statistically significant differences in postoperative outcomes and overall survival between the "converted" group and the propensity-matched "elective on-pump" group. CONCLUSIONS: Despite segregation of unplanned CPB conversion cases from elective on-pump cases, patients with comparable preoperative demographic/risk profiles demonstrated better early postoperative outcomes and, possibly, an improved early survival with an off-pump strategy. A considerable proportion of high-risk patients require intraoperative conversion from off-pump to CPB, and this seems associated with suboptimal outcomes; however, there is no significant benefit to employing an elective on-pump strategy over emergent conversion in the high-risk group.

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis†.

OBJECTIVES: Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). METHODS: Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. RESULTS: After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. CONCLUSIONS: Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up.

When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation.

In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed.

Lung transplantation in chronic obstructive pulmonary disease: long-term survival, freedom from bronchiolitis obliterans syndrome, and factors influencing outcome.

OBJECTIVES: Lung transplantation (LTx) remains the definitive treatment for end-stage lung failure, whereas chronic obstructive pulmonary disease (COPD) represents one of the main diagnoses leading to the indication for a transplant. We sought to assess long-term outcomes after LTx in patients diagnosed with COPD and analyze factors influencing outcome in this frequent patient cohort. METHODS: Between January 2007 and November 2013, a total of 88 LTx were performed in patients with COPD in our institution. Patients with emphysema associated with alpha1-antitrypsin deficiency were excluded from this observation. The study design was a retrospective review of the prospectively collected data. A large number of pre-, intra-, and postoperative variables were analyzed including long-term survival and freedom from bronchiolitis obliterans syndrome (BOS). Furthermore, impact of different variables on survival was analyzed. RESULTS: Preoperative donor data indicated a large proportion of marginal donors. While the overall cumulative survival after six yr was 57.4%, the results in terms of BOS-free survival in long-term follow-up were 39.7% after six yr. Patients with COPD were also associated with a low incidence (2.3%) of the need for postoperative extracorporeal life support (ECLS). CONCLUSIONS: Long-term results after LTx in patients with COPD are acceptable with excellent survival, freedom from BOS, and low use of ECLS postoperatively despite permanently increasing proportion of marginal organs used.

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. METHODS: HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. RESULTS: De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS: De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

BACKGROUND: The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. METHODS: Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. RESULTS: Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio [HR] = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512). CONCLUSIONS: Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients.