Current opinion in pediatrics: pediatric lung transplantation in the 21 st century.

The Registry of the International Society for Heart and Lung Transplantation: Fourteenth Pediatric Lung and Heart-Lung Transplantation Report—2011

Primary graft dysfunction grade 3 following pediatric lung transplantation is associated with chronic lung allograft dysfunction

Lung transplantation is an advanced medical therapy reserved for patients with end-stage lung disease. Relative to other solid organ transplants, lung transplantation in children is infrequently performed. The most common etiologies for pediatric lung transplantation worldwide are cystic fibrosis, pulmonary hypertension, and children's interstitial lung disease. To describe our experience in pediatric lung transplants at Israel's largest transplant center. We performed a retrospective review of all pediatric lung transplantations conducted in our center since 1997. We recorded demographic characteristics, indication for transplantation, clinical and laboratory parameters, post-transplant complications, and survival rates. Of 965 lung transplants, 29 (3.0%) were pediatric patients who underwent lung or heart-lung transplants for end-stage lung disease. Age at transplantation ranged from 2 to 18 years, with a median of 14.0 years (IQR 11-15). Primary etiologies for transplantation were cystic fibrosis (44%), pulmonary hypertension (17%), and children's interstitial lung disease (10%). Survival at 1, 5, 10, and 15 years post-transplant were 90%, 65%, 55%, and 20%, respectively, which is consistent with data reported by pediatric lung transplantation registries. The primary cause of mortality post-transplant was chronic lung allograft dysfunction. Four patients (13.8%) underwent re-transplant. There was no association between survival and transplant indication, nor between survival and type of procedure (lung vs. heart-lung transplant). The short- and long-term outcomes from our program are consistent with published registry data. These outcomes may reflect the benefits of a centralized pediatric lung transplant program, supported by a multidisciplinary team trained in high-capacity international centers.

Extended criteria donor lungs do not impact recipient outcomes in pediatric transplantation

For children and adolescents with end-stage chronic parenchymal and vascular pulmonary disease, lung transplantation is often the last therapeutic option. Since the first pediatric lung transplant in 1986 [1], the management of pediatric patients has developed rapidly, and currently lung transplantation is an accepted treatment in carefully selected children and adolescents, offering a net survival benefit and an improved quality of life [2–4]. While the overall survival after pediatric lung transplant has improved in recent years, rates of chronic lung allograft dysfunction (CLAD) and late mortality have essentially remained unaltered [2, 4]. Thus, the latest improvements have resulted from a reduction in early mortality, mainly due to infectious complications [2, 4]. According to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant (TTX) Registry, a total of 101 pediatric lung transplants were performed worldwide in 2017. These cases were distributed among 37 centers, but only 5 centers performed more than 4 procedures [5]. While most pediatric lung transplants are performed in high-volume adult centers achieving excellent results [6], recent publications have shown that also the centers’ pediatric experience greatly influences the outcome [7]. Especially for the management of patients with cystic fibrosis (CF) undergoing lung transplant, pediatric and CF-specific knowledge is crucial, predicting better long-term survival [7].

20 - Pediatric Lung Transplantation

This article is not an overview of all facets of lung transplantation in cystic fibrosis (CF), but rather it is intended as a review of current allocation controversies, as well as of trends in diagnostics and management in lung transplant recipients and in patients with end-stage lung disease. Despite changes in donor and recipient selection, long-term survival in pediatric lung transplant has continued to be limited by chronic lung allograft dysfunction (CLAD). Due to, in part, this short survival benefit, transplant continues to be an appropriate option for only a subset of pediatric patients with CF. The feasibility of transplant as a therapeutic option is also affected by the limited pediatric organ supply, which has moreover contributed to controversy over lung allocation. Debates over the allocation of this scarce resource, however, may also help to drive innovation in the field of lung transplant. Longer pretransplant survival-as aided by new lung bypass technologies, for example-could help to alleviate organ shortages, as well as facilitate the transport of organs to suitable pediatric recipients. Improved diagnosis and treatment for CLAD and for antibody-mediated rejection have the potential to extend survival in pediatric lung transplant. Regardless, the relative rarity of transplant could pose future challenges for pediatric lung transplant programs, which require adequate numbers of patients to maintain proper expertise.

67 - Pediatric Lung Transplantation

Anti-HLA DQ Antibodies Are Associated with Chronic Lung Allograft Dysfunction in a Pediatric Lung Transplant Population

Two decades of pediatric lung transplant in the United States: Have we improved?

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.

Chronic lung allograft dysfunction (CLAD) continues to negatively impact the survival of pediatric lung transplant (LTx) recipients. Current consensus guidelines are adult-focused. We sought to examine CLAD detection and monitoring practices at pediatric LTx programs. We conducted a survey among the International Pediatric Lung Transplant Collaborative. Questions consisted of practitioner's experience, LTx program demographics, and querying tests used for CLAD surveillance and detection. Investigations queried included: chest x-ray (CXR), chest computed tomography (CT), lung magnetic resonance imaging (MRI), ventilation/perfusion scanning, conventional pulmonary function testing (PFT), multiple breath washout (MBW), infant/preschool PFT, bronchoalveolar lavage, transbronchial biopsies (TBBx), or other tissue sampling techniques. Preferences for certain modalities over others were questioned based on a five-point Likert scale. Twenty-four of 25 programs responded. Chest CT and CXR are used generally for both CLAD surveillance and detection. No programs use lung MRI clinically, it may have some utility in the future. While all centers use conventional PFT, MBW, and infant/preschool PFT are used in one-fifth and one-third of centers, respectively. While the majority of programs use TBBx, only 41.7% would obtain a diagnosis based on tissue histopathology over noninvasive techniques if CLAD is suspected. Utilization of biomarkers is still limited. Our results indicate continued use of conventional PFT along with chest CT and less so CXR for CLAD detection and monitoring in the large majority of centers. Infant/preschool PFTand novel methods such as MBW are used in a few centers only. Respondents agreed there is a timely need for pediatric consensus guidelines on CLAD detection and monitoring.

Pediatric lung transplantation is a life-saving procedure for children with end-stage lung disease. As immunosuppression and treatment have improved, so too have survival outcomes; however, pediatric lung transplant recipients still face challenges, including acute rejection, infection, and long-term issues such as chronic lung allograft dysfunction (CLAD). This review details early complications following pediatric lung transplantation and provides an explorative investigation of the mechanisms underlying acute allograft dysfunction, and current prevention and treatment strategies. Focus is then given to CLAD with an overview of the subtypes of CLAD, review of recognized risk factors, challenges around diagnostics, current treatment strategies, and importantly future research goals to aid in the better identification and characterization of CLAD. As our understanding of acute and CLAD has evolved over time so have prevention and treatment strategies, including the assessment and treatment of risk factors such as infection and aspiration. The diagnosis of CLAD, however, remains extremely challenging with limited treatment options. Future research should focus on the prevention of CLAD.

What we expected all along: Bronchiolitis obliterans syndrome is not specific for bronchiolitis obliterans in pediatric lung transplantation!

For infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long-term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra-corporal life support as "bridge to transplantation". In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post-transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence-based data on immunosuppression are scarce. Drug-related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long-term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re-transplant; however, numbers of pediatric patients undergoing lung re-transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate.