Search

Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABOcompatibility, and donor size. HLAmatching is not routinely considered; however, the presence or later development of anti‐HLAantibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLAincompatibility was a significant predictor of CLAD. One hundred seventy‐five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post‐LTx monitoring was continued for at least 12 months, or until patient death. HLAtyping was performed by sequence‐based typing and Luminex sequence‐specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA‐DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD(hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71–8.29 p < 0.001). When bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) were analyzed independently, HLA‐DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS(HR8.3, 95% CI: 2.46–27.97 p < 0.001) but not BOS(HR1.92, 95% CI: 0.64–5.72, p = 0.237). HLA‐A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor–recipient immune compatibility in LTx. Using the HLAMatchmaker algorithm, the authors show that total Class II eplet mismatch is a significant predictor of restrictive allograft syndrome but not bronchiolitis obliterans syndrome in chronic lung allograft dysfunction.

Lung transplantation (LTx) is a therapeutic option for severe pulmonary arterial hypertension (PAH) patients failing optimal medical therapy. The use of donation after circulatory determination of death (DCDD) donor lungs for PAH LTx has rarely been reported, primarily reflecting concerns that DCDD lungs represent extended criteria donors, at risk of morbidity and mortality. A retrospective study of all Alfred Hospital DCDD and DNDD (donation after neurologic determination of death) PAH LTx was undertaken. Protocolized fluid/inotrope/ventilator and extracorporeal membrane oxygenation (ECMO) strategies were utilized. Since our first DCDD LTx in 2006, 512 LTx have been performed. Of 31 PAH recipients, 11 received DCDD lungs (11% of DCDD LTx) and 20 received DNDD lungs (5% of DNDD LTx) (p = 0.04). Only one PAH patient died on the LTx waiting list. Peri‐LTx ECMO was utilized in 3/11 (27%) DCDD and 6/20 (30%) DNDD PAH LTx (p = 0.68). Primary graft dysfunction, intensive care, and overall stay were the same in both groups. Survival at 1 and 8 years was 100% and 80% for DCDD versus 100% and 70% for DNDD LTx (p = 0.88), respectively. In conclusion, excellent results can be achieved for PAH LTx. DCDD donor lungs are not extended lungs per se having passed the toughest test. Pulmonary arterial hypertension patients can achieve excellent lung transplant outcomes when utilizing donation after circulatory determination of death lung donors.

This case series examines six patients with X‐linked agammaglobulinemia and tracks their post–lung transplant course to highlight the challenges of immunosuppression and infection as well as chronic lung allograft dysfunction in these patients.

The authors describe the first reported case of proven donor‐derived transmission of coxsackievirus serogroup‐3, an enterovirus, following solid organ transplant.

Unexpected donor-to-recipient infectious disease transmission is an important, albeit rare, complication of solid organ transplantation. Greater work and understanding about the epidemiology of these donor-derived transmissions is continually required to further mitigate this risk. Herein we present the first reported case of proven donor-derived transmission of coxsackievirus serogroup-3, an enterovirus, following solid organ transplant. Swift and effective communication between the organ donation agency, treating physicians, laboratory testing and notification ensured a coordinated approach. The resulting clinical syndromes in the organ recipients were mild. This case highlights the requirement for ongoing surveillance over a broad range of infecting pathogens that may present as a donor-derived infection.

This randomized placebo‐controlled trial of induction therapy in lung transplantation demonstrates that a single early posttransplant dose of ATG‐Fresenius does not reduce acute cellular rejection, graft loss, or death within the first year of lung transplantation.

With ABO blood group incompatibility (ABOi) between donor and recipient becoming a part of mainstream living‐donor renal transplantation, the applicability of ABOi to other areas of transplantation is being reconsidered. Here we present a case of inadvertent ABOi lung retransplantation managed successfully with initial plasmapheresis, antithymocyte globulin and intravenous immunoglobulin; and subsequently with oral cyclophosphamide and sirolimus in addition to tacrolimus and prednisolone. Interestingly, in the setting of solid levels of tacrolimus and sirolimus, the patient developed a fatal thrombotic microangiopathy of uncertain origin subsequent to the cessation of cyclophosphamide at 9 years posttransplant. It is apparent that ABOi lung transplantation can result in surprisingly successful long‐term outcomes. Low pretransplant antibody titers likely aid this and, in pediatric neonatal or infant cases, this may not be uncommon. We must proceed cautiously as there are significant risks. Understanding the monitoring, prevention and treatment of lung transplant antibody‐mediated rejection, while avoiding the long‐term complications of overimmunosuppression, will be the keys to the success of future cases.

Early studies reported cytomegalovirus (CMV) pneumonitis as a risk factor for development of bronchiolitis obliterans syndrome (BOS) following lung transplantation. While improvements in antiviral prophylaxis have resulted in a decreased incidence of CMV pneumonitis, molecular diagnostic techniques allow diagnosis of subclinical CMV replication in the allograft. We hypothesized that this subclinical CMV replication was associated with development of BOS. We retrospectively evaluated 192 lung transplant recipients (LTR) from a single center between 2001 and 2009. Quantitative (PCR) analysis of CMV viral load and histological evidence of CMV pneumonitis and acute cellular rejection was determined on 1749 bronchoalveolar lavage (BAL) specimens and 1536 transbronchial biopsies. CMV was detected in the BAL of 41% of LTR and was significantly associated with the development of BOS (HR 1.8 [1.1–2.8], p = 0.02). This association persisted when CMV was considered more accurately as a time‐dependent variable (HR 2.1 [1.3–3.3], p = 0.003) and after adjustment for significant covariates in a multivariate model. CMV replication in the lung allograft is common following lung transplantation and is associated with increased risk of BOS. As antiviral prophylaxis adequately suppresses CMV longer prophylactic strategies may improve long‐term outcome in lung transplantation.

Early studies reported cytomegalovirus (CMV) pneumonitis as a risk factor for development of bronchiolitis obliterans syndrome (BOS) following lung transplantation. While improvements in antiviral prophylaxis have resulted in a decreased incidence of CMV pneumonitis, molecular diagnostic techniques allow diagnosis of subclinical CMV replication in the allograft. We hypothesized that this subclinical CMV replication was associated with development of BOS. We retrospectively evaluated 192 lung transplant recipients (LTR) from a single center between 2001 and 2009. Quantitative (PCR) analysis of CMV viral load and histological evidence of CMV pneumonitis and acute cellular rejection was determined on 1749 bronchoalveolar lavage (BAL) specimens and 1536 transbronchial biopsies. CMV was detected in the BAL of 41% of LTR and was significantly associated with the development of BOS (HR 1.8 [1.1–2.8], p = 0.02). This association persisted when CMV was considered more accurately as a time-dependent variable (HR 2.1 [1.3–3.3], p = 0.003) and after adjustment for significant covariates in a multivariate model. CMV replication in the lung allograft is common following lung transplantation and is associated with increased risk of BOS. As antiviral prophylaxis adequately suppresses CMV longer prophylactic strategies may improve long-term outcome in lung transplantation.

CMV-specific immunity was assessed in a longitudinal cohort of 39 lung transplant recipients (LTR) who were followed prospectively from the time of transplant using a novel assay. At the time of surveillance bronchoscopy, CMV-specific CD8T-cell responses were assessed in the peripheral blood, using the QuantiFERON®-CMV assay, which measures IFN-?-secreting T cells following stimulation with CMV peptides. In total, 297 samples were collected from 39 LTR (CMV DR?, n 8; DR, n 18; D?R, n 6; D?R?, n 7). CMV-specific T-cell immunity was not detected in any of the CMV D?R? LTR. In CMV seropositive LTR levels of CMV immunity were lowest early posttransplant and increased thereafter. While levels of CMV-specific immunity varied between LTR, measurements at any one time point did not predict episodes of CMV reactivation. In CMV mismatched (DR?) LTR, primary CMV immunity was not observed during the period of antiviral prophylaxis, but typically developed during episodes of CMV reactivation. Measuring CMV-specific CD8T-cell function with the QuantiFERON®-CMV assay provides insights into the interrelationship between CMV immunity and CMV reactivation in individual LTR. A better understanding of these dynamics may allow the opportunity to individualize antiviral prophylaxis in the future.

Alloimmune hemolysis is a recognized but infrequent complication of solid organ transplantation, particularly where there is incompatibility within the ABO blood group system. We describe severe hemolysis due to passenger lymphocyte syndrome (PLS) in all three recipients of organs from a single donor with multiple red cell (RC) alloantibodies. The first patient, a liver transplant recipient, required augmentation of immunosuppression to treat immune hemolysis due to anti-B, -D, -C and -Cellano (k). This is the first description of PLS caused by alloantibody to the high incidence RC antigen, k. The two single lung transplant recipients developed hemolysis due to anti-D. Both required escalation of immunosuppression and early transfusion support. Three months posttransplant, all three patients have ongoing evidence of compensated hemolysis. This series highlights the potential for severe non-ABO-mediated immune hemolysis following solid organ transplantation. A positive donor RC antibody screen should prompt careful monitoring of organ recipients for hemolysis.

Despite the potentially high burden of cytomegalovirus (CMV)‐related disease following lung transplantation, the role of the cytotoxic T‐lymphocyte (CTL) response to CMV in this patient group is ill‐defined. We assessed the CMV‐specific T‐cell response in the blood and lung allograft of immunosuppressed lung transplant recipients receiving antiviral prophylaxis and following their withdrawal. While the proportion of CMV‐specific CTL varied between patients, in the absence of CMV reactivation the level of CMV‐specific CD8+T cells in the blood remained stable over time. In the majority of patients CMV‐specific cells could be detected in the lung allograft, often in the absence of viral DNA. Additionally, following primary CMV lung infection, CMV‐specific CD8+T cells were detected no earlier than 100 days post‐transplantation but still prior to the detection of viral DNA in the lung allograft. Together these findings suggest that very low levels of CMV replication are sufficient to both prime and recruit CMV‐specific CD8+T cells to the MHC‐mismatched lung allograft. The direct detection of CMV‐specific T cells with an effector phenotype in the lung allograft suggests a protective antiviral function. This study provides a framework upon which the association between CMV and chronic allograft rejection can be further studied.

Despite the potentially high burden of cytomegalovirus (CMV)-related disease following lung transplantation, the role of the cytotoxic T-lymphocyte (CTL) response to CMV in this patient group is ill-defined. We assessed the CMV-specific T-cell response in the blood and lung allograft of immunosuppressed lung transplant recipients receiving antiviral prophylaxis and following their withdrawal. While the proportion of CMV-specific CTL varied between patients, in the absence of CMV reactivation the level of CMV-specific CD8+T cells in the blood remained stable over time. In the majority of patients CMV-specific cells could be detected in the lung allograft, often in the absence of viral DNA. Additionally, following primary CMV lung infection, CMV-specific CD8+T cells were detected no earlier than 100 days post-transplantation but still prior to the detection of viral DNA in the lung allograft. Together these findings suggest that very low levels of CMV replication are sufficient to both prime and recruit CMV-specific CD8+T cells to the MHC-mismatched lung allograft. The direct detection of CMV-specific T cells with an effector phenotype in the lung allograft suggests a protective antiviral function. This study provides a framework upon which the association between CMV and chronic allograft rejection can be further studied.

The lung donor pool is expanding via access to donation after circulatory determination of death lungs and novel lung donor ex vivoassessment and intervention. See article by Machuca et al on page 993.

To determine the frequency of chronic vascular rejection (CVR) in the lung allograft and its association with donor-specific antibodies (DSA) in the serum, and features of acute antibody-mediated rejection (AMR) in transbronchial biopsies (TBBx).