Pediatric lung transplantation as standard of care

Abstract

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.

The changing landscape of pediatric lung transplantation

“…To date, four of these CFTR modulators have become licensed throughout countries in North America, Europe, and Australia for clinical use in individuals with CF: ivacaftor (Kalydeco®), lumacaftor/ivacaftor (Orkambi®), tezacaftor/ivacaftor (Symdeko®/Symkevi®), and most recently elexacaftor/tezacaftor/ivacaftor (Trikafta®). Together, these medications could benefit around 90% of individuals with CF depending on the underlying genetic defect, with a substantial positive impact anticipated on the lives of both children and adults with CF 7,24–27 …”

“…Together, these medications could benefit around 90% of individuals with CF depending on the underlying genetic defect, with a substantial positive impact anticipated on the lives of both children and adults with CF. 7,[24][25][26][27] One study that examined data from the United Kingdom and the U.S.…”

Optimization of initial dose regimen of tacrolimus in paediatric lung transplant recipients based on Monte Carlo simulation

“…At present, approximately 4000 lung transplants are performed worldwide each year, 2 and since the late 1980s, the International Registry of Heart and Lung Transplantation has reported more than 2200 children with lung transplants 3 . Lung transplant is the last treatment option for infants, children, and adolescents with advanced pulmonary parenchymal and vascular diseases 4 …”

CFTR Modulator Therapy and Its Impact on Lung Transplantation in Cystic Fibrosis

“…Just over three decades later, lung transplantation is considered an accepted therapeutic option children and adults with progressive ACFLD if compatible with goals of care [4,60]. If transplant candidates are optimally selected, a net survival benefit and improved health-related quality of life can be expected [4,[61][62][63]. Historically, CF is the third most common primary indication for lung transplantation in adults, following chronic obstructive pulmonary disease and idiopathic interstitial pneumonia [8].…”

“…Also, in children with CF, overall survival following lung transplantation is nowadays comparable to that in adults [ 60 , 64 ]. However, adolescent lung transplant recipients—predominantly individuals with CF—have poorer overall survival than younger children and adults, with 15- to 19-year-old patients experiencing the highest risk of death [ 60 , 63 , 80 ]. Median survival in pediatric lung transplant recipients was 7 years for patients undergoing lung transplantation during the period from 2008 to 2016 according to the ISHLT Thoracic Transplant Registry report [ 81 ].…”