Lung Transplantation In Children Research Articles

ECMO Bridge to Lung Transplant in Children with Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) represents an important clinical indication for lung transplant (LTx) in children. Recent trends show fewer children with IPAH are undergoing LTx nowadays compared to previous time periods, including those with most severe form of the disease. Using the UNOS Registry, we investigated if ECMO at the time of transplant impacts post-transplant survival in children with IPAH. A total of 74 LTx recipients while on ECMO at the time of transplant were identified (IPAH: N=12). Children with IPAH who underwent LTx while on ECMO had shown comparable survival rates to those who were on ECMO for other conditions. This analysis provides encouraging results, supporting the potential expansion of LTx for this patient population. Given the low number of children undergoing LTx, we think there should be a consensus document to provide better guidance for referring and selecting the high-risk pediatric population with IPAH on ECMO for lung transplant.

Long-Term Outcomes After Lung Transplantation in Children With Intellectual Disabilities.

The United Network for Organ Sharing (UNOS) started recording data on intellectual disability status in 2008. This study aimed to characterize the long-term outcomes for children with intellectual disabilities (IDs) undergoing lung transplantation. All pediatric patients (under 18 years old) undergoing bilateral lung transplantation were identified using the UNOS database. The patients were grouped into the following categories: no cognitive delay, possible cognitive delay, and definite cognitive delay. The primary endpoint was graft survival at 3-year posttransplantation. Multivariate Cox proportional hazards modeling was used to estimate the independent effect of cognitive disability on graft survival. Five hundred four pediatric patients who underwent lung transplantation between March 2008 and December 2022 were retrospectively analyzed. 59 had a definite cognitive delay (12%), 23 had a possible delay (5%), and 421 had no delay (83%). When comparing these three groups, there was no significant difference in 60-day graft survival (p = 0.4), 3-year graft survival (p = 0.6), 3-year graft survival for patients who survived at least 60-day posttransplantation (p = 0.9), distribution of causes of death (p = 0.24), nor distribution treatment of rejection within 1-year posttransplantation (p = 0.06). Intellectual disability does not impact long-term outcomes after bilateral lung transplantation. Intellectual disability should not be a contraindication to bilateral lung transplantation on the basis of inferior graft survival.

Anesthesia for lung transplantation in children under 12 years of age: a single center experience of China

PurposeThis study aims to provide a comprehensive overview of anesthesia management strategies employed in pediatric lung transplantation.MethodsA retrospective analysis was conducted on data from 14 pediatric patients who underwent lung transplantation at the Wuxi Center between September 2019 and November 2022. Patient demographics, surgical particulars, airway management, utilization of extracorporeal support, fluid administration, blood gas and electrolyte profiles, and postoperative outcomes were systematically documented and subsequently summarized.ResultsOf the 14 patients, 7 received extracorporeal membrane oxygenation (ECMO) and 1 received cardiopulmonary bypass (CPB). The average operation time was 303 ± 53 min, with the median extubation time of 26 h. The entirety of pediatric lung transplant procedures was executed successfully, resulting in the discharge of thirteen patients postoperatively. Regrettably, one patient died due to infectious shock on the fourth postoperative day.ConclusionThe achievement of successful pediatric lung transplantation necessitates effective perioperative anesthesia management, with a focal emphasis on circulatory control. Real-time measurements serve as the cornerstone for decision-making. Proactive administration of vasoactive agents is integral to sustaining hemodynamic stability. The judicious assessment of ECMO necessity is paramount, favoring central ECMO during the surgical intervention.

Lung transplantation in children.

Lung transplantation is a well-established treatment for children facing advanced lung disease and pulmonary vascular disorders. However, organ shortage remains highest in children. For fitting the small chest of children, transplantation of downsized adult lungs, lobes, or even segments were successfully established. The worldwide median survival after pediatric lung transplantation is currently 5.7 years, while under consideration of age, underlying disease, and peri- and posttransplant center experience, median survival of more than 10 years is reported. Timing of referral for transplantation, ischemia-reperfusion injury, primary graft dysfunction, and acute and chronic rejection after transplantation remain the main challenges.

Disparities in lung transplantation in children.

Lung transplantation is a recognized therapy for end-stage respiratory failure in children and young people. It is only available in selected countries and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear from data from studies in adults, and from studies in other solid organ transplants in children, that systemic inequities exist in this field. While data relating specifically to pediatric lung transplantation are relatively sparse, professionals should be aware of the risk that healthcare systems may result in disparities in access and outcomes following lung transplantation in children.

(401) Outcomes of ECMO as Bridge to Lung Transplant in Children with Pulmonary Hypertension

(401) Outcomes of ECMO as Bridge to Lung Transplant in Children with Pulmonary Hypertension

Atrial tachyarrhythmias after lung transplantation in children: Acommon occurrence.

Atrial arrhythmia's (AA) following lung transplant in adults are a well-described clinical finding. In pediatrics, however, there are limited data with some reports suggesting that arrhythmias are rare. We performed a single-center retrospective review of lung transplant recipients from January 2013 to June 2020. A detailed evaluation of clinical characteristics, presence of arrhythmias, and outcomes was completed. Arrhythmias were documented based on inpatient telemetry or remote Holter monitoring. Analyses assessing risk factors for arrhythmias and associations with clinical outcomes were performed. Ninety-one lung transplants were performed in 90 patients. Post-operative AA occurred following 19% transplants. Ectopic atrial tachycardia was seen in 14%, atrial flutter in 2%, and a combination in 2%. The majority of these arrhythmias occurred within the first 45 days post-operatively. Antiarrhythmic treatment was required in 59%, but none required ablation or electrical cardioversion. In patients followed for a year or more, 88% had resolution of their arrhythmia. Arrhythmias were not associated with mortality. In further analysis, however, the presence of arrhythmia was associated with an increased length of ICU stay (median of 12 days (IQR 6, 23) versus 5 days (IQR 4, 9); p=.019) and overall length of hospital stay (median of 26 days (IQR 19, 36) versus 17 days (IQR 19, 36); p=.043). Atrial tachyarrhythmias after lung transplantation are common in the pediatric population and usually occur early. Although they frequently require medical therapy and are associated with longer stays, there is no associated increased mortality. In addition, the arrhythmias typically self-resolve.

The changing landscape of pediatric lung transplantation.

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indications by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first-time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria.

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

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). 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. 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. 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.

Serial Assessment of Tricuspid Annular Plane Systolic Excursion Is Associated with Death or Lung Transplant in Children with Pulmonary Arterial Hypertension

Pediatric pulmonary arterial hypertension (PAH) may be classified as primary/idiopathic or may be associated with congenital heart (CHD) or lung disease.1 Right ventricular (RV) function over time determines morbidity and mortality.1 Tricuspid annular plane systolic excursion (TAPSE), a measure of RV longitudinal function, is associated with outcomes in adults with PAH,2 but serial pediatric data are limited and are mostly from a single cohort.3,4 Our prior cross-sectional work established that among several echocardiographic parameters, TAPSE best reflects RV stroke work, a measure of RV efficiency in relation to its loading, which is associated with clinical outcomes.

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.

The use of aerosolized - Adrenergic agonist therapy after lung transplantation in pediatric age

It is my opinion the use of aeresolized –adrenergic agonist such as salbutamol may be helpfull not only to reduced the early mortality but also the chronic allograft dysfunction after lung transplantation in children The reduction of pulmonary edema could be prevent the induction of Obstructive Bronchiolites Syndrome (less pneumonia and viral infections etc) such as the primary graft dysfunction.As we know by international literature Lung transplantation continues to suffer from less-than-ideal long-term outcomes, even in pediatric patients.

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

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. 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. 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. After lung transplantation, an IVIG-based treatment for eDSA yielded high eDSA clearance. IVIG and control patients showed similar CLAD-free and graft survival.

Organ Transplantation for Cystic Fibrosis.

Cystic fibrosis (CF) remains the most common indication for lung transplantation in children and the third most common in adults and has the highest median survival posttransplant for all pretransplant diagnoses. Criteria for transplant in patients with CF vary widely among transplant centers and early referral to multiple centers may be needed to maximize opportunities for lung transplantation. Comorbidities unique to CF such as resistant and atypical pathogens like Burkholderia and Mycobacterium abscessus, and cirrhosis require special consideration for lung transplantation but should not be considered as absolute contraindications. For those patients who are listed for lung transplantation, mechanical support with extracorporeal membrane oxygenation and mechanical ventilation can be efficacious as bridges to lung transplantation in experienced centers with adequate resources. Liver and pancreas transplantations are also acceptable options for end-organ disease related to CF and can provide improvements in both quantity and quality of life.

Five-Year Experience with Treatment of Early Donor Specific Anti-HLA Antibodies in Pediatric Lung Transplant Recipients

Purpose Experience with treatment of early donor specific anti-HLA antibodies (eDSA) after lung transplantation in children is very limited. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins (Pentaglobin, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aim of this study was to present the 5-year results of the IgGAM-based therapy in pediatric lung recipients. Methods Records of pediatric ( Results During the study period, among the 60 lung-transplanted pediatric patients (median age 13 years), 26 (43%) formed the IgGAM group and 33 (55%) the control group. One (2%) patient was treated only with PE and Rituximab and not considered in the study. Among the 26 IgGAM patients, 14 (54%) showed only eDSA (possible subclinical antibody-mediated rejection, AMR). The remaining 12 (46%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 23 (14, 64) days after transplantation. As of October 2018, treatment was completed in 23 (88%) patients. Under IgGAM treatment eDSA cleared in 22 (96%) patients. At follow-up, 5 (20%) IgGAM vs. 5 (15%) control patients developed hypogammaglobulinemia requiring substitution (p=0.73). No IgGAM vs. 3 (10%) control patients developed post-transplant lymphoproliferative disease (p=0.25). At 5 years, graft survival (%) was 76 vs. 84 (p=0.78); freedom (%) from chronic lung allograft rejection (CLAD) was 88 vs. 75 (p=0.54), and from infection requiring hospitalization 53 vs. 23 (p= 0.021), in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, an IgGAM-based treatment for eDSA yielded high eDSA clearance while decreasing the risk of severe infections. IgGAM patients showed 5-year CLAD-free survival at least as good as control patients without eDSA.

Lung Transplantation in Children and Young Adults in Czech Republic: A Single Center Experience

Lung transplantation is an accepted therapeutic option not only in adults, but also in children at the terminal stage of chronic lung diseases. We report our 20 years experience of pediatric lung transplantations at a single center in Czech Republic.

Pediatric lung transplantation.

Pediatric lung transplantation has been undertaken since the 1980s, and it is today considered an accepted therapy option in carefully selected children with end-stage pulmonary diseases, providing carefully selected children a net survival benefit and improved health-related quality of life. Nowadays, >100 pediatric lung transplants are done worldwide every year. Here, specific pediatric aspects of lung transplantation are reviewed such as the surgical challenge, effects of immunosuppression on the developing pediatric immune system, and typical infections of childhood, as it is vital to comprehend that children undergoing lung transplants present a real challenge as children are not 'just small adults'. Further, an update on the management of the pediatric lung transplant patient is provided in this review, and future challenges outlined. Indications for lung transplantation in children are different compared to adults, the most common being cystic fibrosis (CF). However, the primary diagnoses leading to pediatric lung transplantation vary considerably by age group. Furthermore, there are regional differences regarding the primary indication for lung transplantation in children. Overall, early referral, careful patient selection and appropriate timing of listing are crucial to achieve real survival benefit. Although allograft function is to be preserved, immunosuppressant-related side effects are common in children post-transplantation. Strategies need to be put into practice to reduce drug-related side effects through careful therapeutic drug monitoring and lowering of target levels of immunosuppression, to avoid acute-reversible and chronic-irreversible renal damage. Instead of a "one fits all approach", tailored immunosuppression and a personalized therapy is to be advocated, particularly in children. Further, infectious complications are a common in children of all ages, accounting for almost 50% of death in the first year post-transplantation. However, chronic lung allograft dysfunction (CLAD) remains the major obstacle for improved long-term survival.

Lung Transplantation in Children

Lung Transplantation in Children

Bronchial artery revascularization and en bloc lung transplant in children

Long-term success in pediatric lung transplantation is limited by infection and bronchiolitis obliterans syndrome (BOS). The bilateral sequential lung transplantation (BSLT) technique may result in airway ischemia leading to bronchial stenosis, dehiscence, or loss of small airways. En bloc lung transplant (EBLT) with bronchial artery revascularization (BAR) minimizes airway ischemia, thus promoting superior airway healing. BAR also allows for safe tracheal anastomosis, circumventing the need for bilateral bronchial anastomoses in small children. This was a retrospective review of bilateral transplantations from 2005 to 2014. Both techniques were used in parallel. Redo and multiorgan transplants were excluded. There were 119 recipients comprising 88 BSLTs and 31 EBLTs. Follow-up time was 3 years (interquartile range, 1-5 years). Donor ischemic and cardiopulmonary bypass times were not different between techniques (p = 0.48 and p = 0.18, respectively). Degree of graft dysfunction and cellular rejection scores were not different (p = 0.83 and p = 0.93, respectively). There were 3 hospital deaths after BSLT and 2 after EBLT (p = 0.60). Overall survival was 61% for the BSLT group and 77% for the EBLT group (p = 0.54). Freedom from BOS was 71% in the BSLT group and 94% in the EBLT group (p = 0.08). On routine bronchoscopy, 57% BSLT and 16% EBLT patients had 1 or more airway ischemic findings (p < 0.0001). Multivariate analysis showed BSLT was associated with higher ischemic injury (relative risk, 2.86; 95 confidence interval, 1.3-6.5; p = 0.01) and non-airway complications (relative risk, 4.62; 95% confidence interval, 1.1-20.2; p = 0.04) but not airway reinterventions (p = 0.07). Airway dehiscence occurred in 3 BSLT patients. Pediatric EBLT with BAR can be safely performed without increasing operative or graft ischemic times. Airway ischemia and non-airway complications were significantly reduced when BAR was combined with tracheal anastomosis, potentially diminishing morbidity caused by anastomotic healing complications.

Current State of Pediatric Lung Transplantation.

Cardiothoracic transplantation has significantly impacted the lives of pediatric patients with advanced cardiopulmonary failure. The current state of lung transplantation in children as well as its ongoing and future challenges are discussed.