Survival in lung transplant recipients (LTRs) lags behind heart, liver, and kidney transplant, in part due to the direct and indirect effects of infection. LTRs have increased susceptibility to ...infection due to the combination of a graft continually exposed to the outside world, multiple mechanisms for impaired mucus clearance, and immunosuppression. Community-acquired respiratory viral infections (CARVs) are common in LTRs. Picornaviruses have roughly 40% cumulative incidence followed by respiratory syncytial virus and coronaviruses. Although single-center retrospective and prospective series implicate CARV in rejection and mortality, conclusive evidence for and well-defined mechanistic links to long-term outcome are lacking. Treatment of viral infections can be challenging except for influenza. Future studies are needed to develop better treatments and clarify the links between CARV and long-term outcomes.
Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart ...and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations.
Objective To compare outcomes of infants and children who underwent lung transplantation for genetic disorders of surfactant metabolism ( SFTPB , SFTPC , ABCA3 , and NKX2-1 ) over 2 epochs (1993-2003 ...and 2004-2015) at St Louis Children's Hospital. Study design We retrospectively reviewed clinical characteristics, mortality, and short- and long-term morbidities of infants (transplanted at <1 year; n = 28) and children (transplanted >1 year; n = 16) and compared outcomes by age at transplantation (infants vs children) and by epoch of transplantation. Results Infants underwent transplantation more frequently for surfactant protein-B deficiency, whereas children underwent transplantation more frequently for SFTPC mutations. Both infants and children underwent transplantation for ABCA3 deficiency. Compared with children, infants experienced shorter times from listing to transplantation ( P = .014), were more likely to be mechanically ventilated at the time of transplantation ( P < .0001), were less likely to develop bronchiolitis obliterans post-transplantation ( P = .021), and were more likely to have speech and motor delays ( P ≤ .0001). Despite advances in genetic diagnosis, immunosuppressive therapies, and supportive respiratory and nutritional therapies, mortality did not differ between infants and children ( P = .076) or between epochs. Kaplan-Meier analyses demonstrated that children transplanted in epoch 1 (1993-2003) were more likely to develop systemic hypertension ( P = .049) and less likely to develop post-transplantation lymphoproliferative disorder compared with children transplanted in epoch 2 (2004-2015) ( P = .051). Conclusion Post-lung transplantation morbidities and mortality remain substantial for infants and children with genetic disorders of surfactant metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
For children with severe pulmonary hypertension, addition of Potts shunt to a comprehensive palliation strategy might improve the outcomes afforded by medications and delay lung transplantation.
A ...prospective analysis was conducted of all children undergoing Potts shunt (first performed in 2013) or bilateral lung transplant for pulmonary hypertension from 1995 to present.
A total of 23 children underwent Potts shunt (20 surgical, 3 transcatheter), and 31 children underwent lung transplant. All children with Potts shunt had suprasystemic right ventricle pressures despite maximal medical treatment. In the majority of patients, the Potts shunt was performed through a left thoracotomy approach (90%, 18/20), by direct anastomosis (65%, 13/20), and without the use of extracorporeal support (65%, 13/20). Perioperative outcomes after Potts shunt were superior to lung transplant including mechanical ventilation time (1.3 vs 10.2 days, P = .019), median hospital length of stay (9.8 vs 34 days, P = .012), and overall complication rate (35% 7/20 vs 81% 25/31, P = .003). Risk factors for operative mortality after Potts shunt (20%, 4/20; compared with 6%, 2/31 for lung transplant, P = .195) included preoperative extracorporeal membrane oxygenation and significant right ventricle dysfunction. In midterm follow-up (median 1.8, maximum 6.1 years), patients with Potts shunt had durable equalization of right ventricle/left ventricle pressures and improved functional status. There was no significant survival difference in patients with Potts shunt and patients with lung transplant (P = .258).
Potts shunt is an effective palliation for children with suprasystemic pulmonary hypertension that may become part of a strategy to maximize longevity and functional status for these challenging patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized ...diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications.
BACKGROUNDAcute rejection (AR) and development of chronic rejection, bronchiolitis obliterans syndrome (BOS) remain major limiting factors for lung transplantation (LTx). This retrospective study is ...to identify differentially expressed circulating microRNAs (miRNAs) that associate with development of AR and BOS in pediatric lung transplant recipients (LTxR).
METHODSWe determined the circulating levels of 7 selected candidate miRNAs in 14 LTxR with AR, 7 with BOS, and compared them against 13 stable pediatric LTxR at 1, 6, and 12 months after LTx. In addition, 6 AR, 7 BOS, and 8 stable pediatric LTxR, 16 AR, 17 BOS, and 16 stable adult LTxR were included for validation.
RESULTSMiR-10a, -195, -133b were significantly lower in AR and miR-144, -142-5p, -155 were higher in AR compared to stable (P < 0.05). In addition, circulating levels of miR-134, -10a, -195, -133b were significantly lower and miR-144, -142-5p, -155 were higher (P < 0.05) with development of BOS. The receiver-operating characteristic demonstrated that miR-142-5p, miR-155, and miR-195 strongly discriminated patients with AR from stable LTxR (P < 0.001 for all comparisons)miR-142-5p (area under the curve AUC, 0.854), miR-155 (AUC, 0.876), and miR-195 (AUC, 0.872). Further, miR-10a, miR-142-5p, miR-144, and miR-155 strongly discriminated BOS from stable LTxR (P < 0.001 for all comparisons).
CONCLUSIONSWe demonstrated that differential expression of circulating miRNAs occurs in LTxR with AR and BOS, suggesting that they can provide not only important clues to pathogenesis but also may serve as potential noninvasive biomarkers for AR and BOS after pediatric LTx.
Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American ...Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS. A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations. The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of post-transplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS. The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention.
Induction therapy in lung transplantation Sweet, Stuart C.
Transplant international,
July 2013, 2013-Jul, 2013-07-00, 20130701, Volume:
26, Issue:
7
Journal Article
Peer reviewed
Open access
Strategies for induction in lung transplant recipients typically mirror those used in other solid organ transplant recipients. Polyclonal (Atgam, RATG) and monoclonal (OKT3) T‐cell depleting agents, ...IL‐2 Receptor antagonists (basiliximab and daclizumab) have been used most commonly. In spite of evidence from ISHLT registry reports that induction reduces acute rejection and has a small benefit in freedom from bronchiolitis obliterans and long‐term survival, other studies have been less convincing in terms of long‐term benefit. Future iterations of induction strategy for lung transplant recipients will hopefully utilize tolerogenic approaches currently being tested in renal transplantation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective To evaluate paracorporeal lung assist devices to treat neonates and children with decompensated respiratory failure as a bridge to recovery or lung transplantation. Methods One neonate (23 ...days old) and 3 young children (aged 2, 9, and 23 months) presented with primary lung disease with pulmonary hypertension, including alveolar capillary dysplasia in 2 and right pulmonary hypoplasia and primary pulmonary hypertension in 1. The patients were listed for lung transplantation but decompensated and required extracorporeal membrane oxygenation (ECMO). The patients were transitioned from ECMO to a pumpless paracorporeal lung assist device (Maquet Quadrox-iD oxygenator in 3, Novalung in 1) with inflow from the pulmonary artery and return to the left atrium. Results The patients were weaned from ECMO and supported by the device for 44 ± 29 days (range, 5-74). Three patients were extubated while supported by the device (after 9, 15, and 72 days). One patient was bridged to lung transplant (9 months old, with alveolar capillary dysplasia, supported 5 days). One patient was bridged to recovery with maximal medical therapy (23 months old, with primary pulmonary hypertension, supported 23 days). Two patients died while awaiting a suitable lung donor after a support time of 54 and 72 days. Conclusions Pediatric patients bridged from ECMO to lung transplantation have poor results. An alternative method for longer term respiratory support was necessary as a bridge for these patients. The use of a paracorporeal lung assist device successfully supported 4 patients to recovery, lung transplantation, or past the average wait time for pediatric donor lungs (27 days). This therapy has the potential to bridge children with decompensated respiratory failure to lung transplantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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