Outcomes of Concomitant Cardiac Surgical Procedures Performed During Pediatric Lung Transplantation in the United States.

Data on concomitant cardiac surgery (CCS) performed during pediatric lung transplantation (LTx) is limited. Therefore, we conducted a multi-institutional analysis to identify the incidence and outcomes of CCS in pediatric (< 18 years) LTx recipients by merging data (2004-2023) from the United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) databases. Of the total of 596 pediatric LTx recipients, 87 (15%) underwent CCS. The majority of these cardiac surgeries were atrial septal defect (ASD) closure (90%) followed by aortic arch/descending aortic repair (3%), atrial repair (3%), ventricular septal defect closure (2%), patent ductus arteriosus ligation (2%), and tricuspid valve repair (2%). The median age at LTx was 3 years (IQR: 0-12). Pulmonary hypertension (PHT) was the predominant indication for LTx (54%). Survival to discharge was 94% and 5-years survival was 64%. Our findings indicate CCS in children undergoing LTx has acceptable outcomes.

Influence of early extubation on post-operative outcomes after pediatric lung transplantation.

Lung transplantation has become an accepted therapeutic option for a select group of children with end-stage lung disease. We evaluated the impact of early extubation in a pediatric lung transplant population and its post-operative outcomes. Single-center retrospective study. PICU within a tertiary academic pediatric hospital. Patients <22 years after pulmonary transplant between January 2011 and December 2016. A total of 74 patients underwent lung transplantation. The primary pretransplantation diagnoses included cystic fibrosis (58%), pulmonary fibrosis (9%), and surfactant dysfunction disorders (10%). Of 60 patients, 36 (60%) were extubated within 24 hours and 24 patients after 24 hours (40%). A total of seven patients (11.6%) required reintubation within 24 hours. Median length of stay for the early extubation group was shorter at 3 days ([(IQR) 2.2-4.7]) compared to 5 days (IQR, 3-7) (P = .02) in the late extubation group. Median costs were lower for the early extubation group with 13,833 US dollars (IQR, 9980-22,822) vs 23 671 US dollars (IQR, 16 673-39 267) (P = .043). Fourteen patients were in the PICU prior to their transplantation; this did not affect their early extubation success. Neither did the fact of requiring invasive or non-invasive mechanical ventilation before transplantation. Early extubation appears to be safe in a pediatric population after lung transplantation and is associated with a shorter LOS and decreased hospital costs. It may prevent known complications associated with mechanical ventilation.

Pediatric lung transplant: Correlation of pretransplant condition with post-transplant outcomes.

BACKGROUND: It is generally accepted that patients who have greater functional capacity are better candidates for lung transplantation. Accurate assessment of physical condition is important in identifying appropriate candidates for transplant. The focus of this study was to determine which measures of pretransplant physical condition correlate with positive post-transplant outcomes in children undergoing lung transplant. METHODS: A retrospective chart review was done on 44 patients, ages 5 to 21 years. The pretransplant data collected included functional status, 6MWT, ambulatory status, and mechanical support. Post-transplant outcome data included time on the ventilator, days in the ICU, length of hospitalization, and 12-month survival. RESULTS: Results were analyzed using Fisher exact and Kruskal-Wallis tests. Patients with limited ambulation had more days in the ICU compared to the most ambulatory group (P = .043). Patients independent or needing some help with ADL had less time on the ventilator compared to patients needing total help. (P = .014). Patients with 6MWT result greater than 500' had fewer ICU days (P = .044) and marginally better 12-month survival (P = .057). The 12-month survival of children needing invasive ventilatory support pretransplant was not significantly worse than those who did not; however, they required significantly more time on the ventilator (P = .004), days in ICU (P = .013), and longer hospitalization. DISCUSSION: This study demonstrated that pretransplant physical condition affects post-transplant outcomes in children. Measures associated with positive post-transplant outcomes were identified and could be beneficial in determining which patients are optimal candidates for lung transplant.

A shifting landscape: Practice patterns and outcomes of cystic fibrosis and non-cystic fibrosis pediatric lung transplantation.

BACKGROUND: New drugs may further decrease the need for lung transplant (LTx) in pediatric patients with cystic fibrosis (CF), but few studies highlight pediatric non-CF LTx characteristics and outcomes. METHODS: The ISHLT registry was used to report morbidity, graft failure, and survival for primary pediatric (<18 years) LTx performed 1990-2017. Recipient/donor characteristics and long-term outcomes were analyzed for CF and non-CF recipients. Survival was assessed using Kaplan-Meier curves. RESULTS: Of 2232 primary LTx, (43% in males), 918 (41%) were performed for non-CF indications; most commonly pulmonary hypertension (43%). Non-CF patients were younger (median age 11 vs. 15, p < .001), and more frequently on inotropes and/or extracorporeal membrane oxygenation (15% vs. 2.4%, p < .001) at transplant, compared to CF recipients. In-hospital major complications more commonly affected CF LTx recipients (57% vs. 48%, p = .003), but 30-day mortality was higher in the non-CF group (9% non-CF vs. 5% CF, p < .001). One-, five-, and ten-year mortality was 18%, 50%, and 65% for CF recipients, respectively, and 21%, 45%, and 58% for non-CF recipients (p = .01 at 10 years). Five-year survival was significantly better for non-CF females versus CF females (56% vs. 48%, p = .013), but was similar between groups for males (55% vs. 54%, p = .305). While age was a late outcomes risk factor, pulmonary hypertension and later transplants eras were protective. CONCLUSIONS: Early mortality is higher and late mortality is lower in non-CF LTx. Current non-CF LTx outcomes leave room for improvement. Further study is needed to evaluate the effects of center volume and pediatric-specific experience on outcomes.

Outcome according to subspecies following lung transplantation in cystic fibrosis pediatric patients infected with Mycobacterium abscessus.

BACKGROUND: Mycobacterium abscessus infection has been associated with variable outcomes following lung transplantation. M abscessus comprises three subspecies (M abscessus subsp abscessus, M abscessus subsp massiliense, and M abscessus subsp bolletii). We investigated whether lung transplantation outcome in cystic fibrosis (CF) patients in a single center was related to the M abscessus subspecies and genetic cluster. METHODS: CF patients with chronic M abscessus infection transplanted at Great Ormond Street Hospital between 2004 and 2017 were retrospectively examined. All M abscessus isolates were identified to subspecies level by polymerase chain reaction and sequencing. Genetic cluster was determined by variable number tandem repeat profiling and whole-genome sequencing (WGS), and sequence type inferred from WGS. RESULTS: Thirteen patients with chronic M abscessus infection underwent heart/lung or lung transplantation. Subspecies identification showed n = 1 with M abscessus bolletii, n = 5 with M abscessus massiliense, and n = 7 with M abscessus abscessus infection. Eight (62%) patients (one with M abscessus massiliense and seven with M abscessus abscessus) died post-lung transplant. The patient with M abscessus bolletii and three patients with M abscessus massiliense did well post-transplant. One patient with M abscessus massiliense is receiving ongoing treatment. CONCLUSIONS: Dramatically worse outcomes are observed in patients infected with M abscessus subspecies abscessus, the majority of whom were infected with ST-1 and ST-26 strains. Patients infected with other M abcsessus strains can have acceptable outcomes.

Pediatric lung transplantation: Results of volume reduction in smaller children.

Pediatric LTX is challenged by the scarcity of suitable donor organs. To alleviate the problem of size matching, volume reduction of the donor is a possible option. Previous reports address mostly older teenagers, and data about younger patients are lacking. The purpose of this study was to investigate whether trimming had influence on the morbidity and mortality in slightly younger recipients, operated in a single center. Between 2015 and 2018, 20 patients were transplanted at the GOSH London. The mean age was 11.5 (±4.6) years. Nine patients underwent volume reduction prior to transplantation (T group). The other patients received classical bilateral LTX (NT group). Ischemia times were longer in the T group, but this difference was not statistically significant. We observed no 30-day mortality. Hospital survival in the T group was 78% vs 90% in the NT group. After almost 3 years, mortality in the T group was 22% vs 28% in the NT group. None of these differences was statistically significant. The mean duration of MV, intensive care stay, and hospital stay were 11.5, 19.9, and 44.8 days, respectively. Results were equal in terms of morbidity, defined as respiratory and neurological complications or the need for ECMO. Results show that volume reduction prior to LTX is a feasible option, even in smaller children. While awaiting long-term results, accepting larger donor organs could be a strategy to further reduce waiting list time and subsequently lower the mortality on the waiting list.

Successful lung donation at the age of 6 weeks: Challenges and lessons learned.

A clinical case of successful procurement and transplantation of bilateral lungs from 6-week-old infant with sepsis secondary to bacterial meningitis is reported. Forty-one-day-old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO2 50.4 kPa (378 mm Hg), pCO2 4.9 kPa (37 mm Hg), on FiO2 100%, PEEP 5 cm H2 O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram-stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4-month-old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6-week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.

Anellovirus loads are associated with outcomes in pediatric lung transplantation.

Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha- and betatorquevirus, two anellovirus genera. The primary short-term outcome of interest was acute rejection, and longer-term outcomes were analyzed individually and as "composite" (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post-transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short-term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer-term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.

Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism.

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.

The evolving potential for pediatric ex vivo lung perfusion.

Despite the rise in the number of adult lung transplantations performed, rates of pediatric lung transplantation remain low. Lung transplantation is an accepted therapy for pediatric end-stage lung disease; however, it is limited by a shortage of donor organs. EVLP has emerged as a platform for assessment and preservation of donor lung function. EVLP has been adopted in adult lung transplantation and has successfully led to increased adult lung transplantations and donor lung utilization. We discuss the future implications of EVLP utilization, specifically, its potential evolving role in overcoming donor shortages in smaller children and adolescents to improve the quality and outcomes of lung transplantation in pediatric patients.

A contemporary analysis of induction immunosuppression in pediatric lung transplant recipients.

There is an increasing trend in the use of induction immunosuppression in children undergoing lung transplantation (LTx). To evaluate the effect of this practice on survival, the United Network for Organ Sharing (UNOS) was queried from 1987 to 2012, restricting analysis to transplant patients 6-17 years old from 2001 to 2012, who received no induction (NONE) or induction (INDUCED) with the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin (ALG), or antithymocyte globulin (ATG). Of 23 951 lung transplants, 330 met inclusion criteria with 177 (54%) being INDUCED. Of the INDUCED agents, 121 (68%) were basiliximab, 3 (2%) alemtuzumab, and 53 (30%) ALG/ATG/thymoglobulin. The mean patient age was 13.6 (SD = 3.2) and 14 (SD = 3.0) years for the INDUCED and NONE groups, respectively. The median survival in the INDUCED group was 77.4 months (95% CI: 46.1, 125.6) compared with 50.8 months (95% CI: 42.9, 61.3) for the NONE (log-rank P-value = 0.3601). The most common cause of death was due to allograft failure or pulmonary complications with only one patient dying from post-transplant lymphoproliferative disorder. The estimated hazard ratio for INDUCED versus NONE was 0.859 (95% CI: 0.620, 1.191; P = 0.3618); there were no significant confounders or effect modifiers among the demographic and clinical variables. In conclusion, antibody-based induction immunosuppression with contemporary agents had a trend toward a protective, but not statistically significant, effect in 6- to 17-year-old patients.

Successful lung transplant in a child with cystic fibrosis and persistent Blastobotrys rhaffinosifermentans infection.

Fungal respiratory infections in patients with CF are a significant concern both pre- and post-lung transplantation (LTx). Fungal infection is associated with increased mortality post-LTx, and in the past decade, the prevalence of fungal colonization in Canadian pediatric patients with CF has increased. The emergence of novel fungal pathogens is particularly challenging to the transplant community, as little is known regarding their virulence and optimal management. We present a case of a successful double-lung transplant in a pediatric patient with CF who was infected pretransplantation with a novel yeast, Blastobotrys rhaffinosifermentans. This patient was treated successfully with aggressive antifungal therapy post-transplantation, followed by extended fungal prophylaxis. The significance of fungal colonization and infection in children with CF pre- and post-LTx is reviewed.

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model.

OBJECTIVE: The method of administering the initial doses of tacrolimus in recipients of pediatric lung transplantation, especially in patients with low hematocrit, is not clear. The present study aims to explore whether weight, CYP3A5 genotype, and voriconazole co-administration influence tacrolimus initial dosage in recipients of pediatric lung transplantation with low hematocrit based on safety and efficacy using a simulation model. METHODS: The present study utilized the tacrolimus population pharmacokinetic model, which was employed in lung transplantation recipients with low hematocrit. RESULTS: For pediatric lung transplantation recipients not carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-13, 13-19, 19-22, 22-35, 35-38, and 38-40 kg are 0.03, 0.04, 0.05, 0.06, 0.07, and 0.08 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-18, 18-30, and 30-40 kg are 0.06, 0.08, 0.11 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients not carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20 and 20-40 kg are 0.02 and 0.03 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20, 20-33, and 33-40 kg are 0.03, 0.04, and 0.05 mg/kg/day, which are split into two doses, respectively. CONCLUSION: The present study is the first to recommend the initial dosages of tacrolimus in recipients of pediatric lung transplantation with low hematocrit using a simulation model.

Living Donor Lung Transplantation After Hematopoietic Stem Cell Transplantation From the Same Donor: A Risk Worth Taking.

Living donor (LD) lung transplantation (LT) represents an exceptional procedure in Western countries. However, in selected situations, it could be a source of unique advantages, besides addressing organ shortage. We report a successful case of father-to-child single-lobe LT, because of the complications of hematopoietic stem cell transplantation from the same donor, with initial low-dose immunosuppressive therapy and subsequent early discontinuation. Full donor chimerism was hypothesized to be a mechanism of transplant tolerance, and this postulated immunological benefit was deemed to outweigh the risks of living donation and the possible drawbacks of single compared with bilateral LT. Favorable size matching and donor's anatomy, accurate surgical planning, and specific expertise in pediatric transplantation also contributed to the optimal recipient and donor outcomes. Ten months after LD LT, the patient's steadily good lung function after withdrawal of immunosuppressive therapy seems to confirm the original hypothesis.

Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

Use of Berlin EXCOR cannulas in both venovenous and venoarterial central extracorporeal membrane oxygenation configurations overcomes the problem of cannula instability while bridging infants and young children to lung transplant.

Objectives: Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant. Methods: We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between 2019 and 2021. Results: Six patients, 2 with pulmonary veno-occlusive disease (15-month-old male and 8-month-old male), 1 with ABCA3 mutation (2-month-old female), 1 with surfactant protein B deficiency (2-month-old female), 1 with pulmonary arterial hypertension in the setting of D-transposition of the great arteries after repair as a neonate (13-year-old male), and 1 with cystic fibrosis and end-stage lung disease, were supported for a median of 56.3 days on extracorporeal membrane oxygenation while awaiting transplantation. All patients were extubated after initiation of extracorporeal membrane oxygenation, participating in rehabilitation until transplant. No complications due to central cannulation and use of the Berlin Heart EXCOR cannulas were observed. One patient with cystic fibrosis developed fungal mediastinitis and osteomyelitis resulting in discontinuation of mechanical support and death. Conclusions: Novel use of Berlin Heart EXCOR cannulas for central cannulation eliminates the problem of cannula instability allowing extubation, rehabilitation, and bridge to lung transplant for infants and young children.

Technical Aspects of Lung Transplantation: Pediatric and Lobar Transplantation.

Fewer patients undergo pediatric lung transplantation (PLT) than adult lung transplantation. Size mismatch is the key factor that limits the availability of potential donors. Every candidate for PLT is in a different scenario in terms of age, height and weight, size of structures, indications for PLT, the concomitant presence of a cardiac anomaly, and other individual-specific factors; thus, a thorough understanding of pediatric patients' medical problems is essential. Living-donor lobar lung transplantation (LDLLT) has only been performed once in Korea to date. However, since each step in the LDLLT is a well-established procedure, including intrapericardial lobectomy, lung procurement, and lobar lung transplantation, qualified surgeons and lung transplantation teams are competent to perform LDLLT in clinically necessary situations.

Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience.

OBJECTIVE: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old). METHODS: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months. RESULTS: Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups. CONCLUSIONS: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.

Lung transplantation for pediatric pulmonary arterial hypertension-quo vadis?

In children with pulmonary arterial hypertension, lung transplantation illustrates a feasible treatment option once pharmacological therapy is exhausted. Timing of listing for lung transplantation in children remains difficult since hemodynamic deterioration often occurs abruptly and the time on the waiting list is usually hard to predict. Clear contraindications for lung transplantation are recent history of malignancies as well as irreversible end-organ failure. Generally, patients with pulmonary arterial hypertension in the absence of structural cardiac defects can safely undergo bilateral lung transplantation, combined heart-lung transplantation remains a procedure with a higher perioperative risk and should only be performed in selected cases with irreversible structural defects. Donor selection in recent years shows donors with extended criteria as well as lobar transplantation with good outcome, having the positive effect of broadening of the donor pool. Bridging to lung transplantation with veno-arterial ECMO treatment is feasible and has a good outcome in experienced transplant centers. Surgical considerations should include the risk of hemodynamic decompensation upon anesthesia induction and the need for extracorporeal support pre-, intra- and postoperative. Lung transplantation should be performed on veno-arterial ECMO support with either peripheral (>20 kg) or central cannulation (<20 kg). The surgical transplantation procedure includes the bronchial anastomosis as well as anastomoses of the pulmonary artery and the left atrium. Postoperative prolonged veno-arterial ECMO treatment for the immediate postoperative period allows for left ventricular remodeling given the new hemodynamic circumstances with lower pulmonary vascular resistance. Standard triple immunosuppression in most lung transplant programs currently includes steroids, mycophenolate mofetil and tacrolimus. Survival after pediatric lung transplantation for IPAH is comparable to pediatric lung transplants for other underlying diseases with a 1-year survival of approx. 80% and a 5-year survival of 64-65%. Therefore, evolving techniques in the field of lung transplantation led to overall improved survival prospects in children with end-stage pulmonary vascular disease.

Six-year experience with treatment of early donor-specific anti-HLA antibodies in pediatric lung transplantation using a human immunoglobulin-based protocol.

OBJECTIVES: Experience with the treatment of early donor-specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, we have treated patients with eDSA since 2013 with successive infusions of intravenous human immunoglobulins (IVIG), combined in some cases with a single dose of Rituximab and plasmapheresis (therapeutic plasma exchange [tPE]) or immunoabsorption. The aim of this study was to present the 6-year results of IVIG-based therapy in pediatric lung recipients. METHODS: Records of pediatric (<18 years old) patients transplanted at our institution between 01/2013 and 03/2019 were reviewed. Outcomes were compared between patients with eDSA treated with IVIG (IVIG group) and without eDSA (control group). Median (interquartile range [IQR]) follow-up amounted to 28 (12-52) months. RESULTS: During the study period, 66 lung-transplanted pediatric patients were included, of which 27 (41%) formed the IVIG group and 38 (57%) the control group. Among the IVIG patients, 14 (52%) patients showed concomitant graft dysfunction (possible clinical antibody-mediated rejection). The median time to eDSA detection was 24 (14-63) days after transplantation. eDSA were cleared in 25 (96%) of the 26 patients which completed treatment. At 3 years, graft survival (%) was 73 vs 85 (P = .65); freedom (%) from chronic lung allograft rejection (CLAD) was 89 vs 78 (P = .82); and from infection 47 vs 31 (P = .15), in IVIG vs control patients, respectively. CONCLUSIONS: After lung transplantation, an IVIG-based treatment for eDSA yielded high eDSA clearance. IVIG and control patients showed similar CLAD-free and graft survival.