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Jump to Key Points The introduction of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators has dramatically transformed pediatric lung transplantation, underscoring the need for a new framework to guide patient selection and timing, said Christian Benden, MD, of director of the pediatric lung transplant program at Boston Children’s Hospital in Boston, at the European Respiratory Society Congress, Barcelona, Spain.
Fewer Transplants for CF
The landscape has changed dramatically with the advent of highly effective CFTR modulators (HEMTs), particularly the combination of elexacaftor, tezacaftor, and ivacaftor. “CF is no longer the dominant pediatric indication,” said Benden, citing data from the International Society for Heart and Lung Transplantation (ISHLT) registry.
Benden noted that the registry is incomplete because some major centers worldwide, including Toronto and Hanover, do not contribute data. Even so, the trends are striking and point to a historic decline in pediatric lung transplantation for CF. In the US, these transplants peaked in 2013 at 32 cases, representing 51.6% of all pediatric lung transplants that year; in Europe, the figure was 60%.
Between 2020 and 2023, CF accounted for only 14.4% of pediatric lung transplants in the US compared to 52.7% between 2016 and 2019.
- HEMT era ↓ pediatric CF lung transplants; CF no longer dominant indication.
- FEV1 <30% alone no longer sufficient for CF transplant referral/listing.
- Some CF children with FEV1 <30% now >2-year life expectancy on HEMTs.
- Childhood ILD, PAH, obliterative bronchiolitis now larger transplant share.
- Very young candidates often need bridge-to-transplant support; donor-size matching limits waits.
“Transplantation remains a treatment option for patients with advanced CF,” explained Benden. But the threshold for referring patients for a transplant can no longer be defined solely based on the physiological parameters used before the era of HEMTs.
The COVID pandemic has also disrupted operations, but the decline in pediatric CF transplants observed in recent years is primarily part of an underlying trend linked to the increasing efficacy of CFTR modulators.
The 30% FEV1 Threshold Is No Longer Sufficient
This development is one of the key points of the new ISHLT consensus, which, for the first time, is specifically dedicated to the management and selection of pediatric candidates for lung transplantation.
“Historical recommendations, particularly for children with CF, associated a forced expiratory volume in 1 second (FEV1) below 30% of the predicted value with the need for multidisciplinary discussion or placement on the transplant list,” recalled Benden. “In the era of HEMTs, this single criterion has become insufficient. The new consensus emphasized that some children with an FEV1 below 30% may now have a life expectancy of more than 2 years, particularly when they respond favorably to new treatments.”
Shifting Indications
The decline in CF has been accompanied by a corresponding shift in the profile of transplant indications. Today, childhood interstitial lung disease, pulmonary arterial hypertension (PAH), and selected forms of obliterative bronchiolitis account for a much larger share of pediatric lung transplant cases.
The international registry also shows a rise in transplants for childhood interstitial lung disease, particularly in North America, where these cases accounted for 27% of pediatric transplants in 2021. Indications related to PAH are also at historic highs, with idiopathic PAH representing nearly 20% of pediatric transplants in the US.
“This shift poses a different challenge than that encountered with CF,” noted Benden. In certain forms of pulmonary vascular disease, a child may maintain a satisfactory clinical condition for a relatively long time, then deteriorate rapidly. Conversely, certain interstitial lung diseases affect very young children with extremely limited respiratory reserve.
Younger Candidates More Difficult to Support
The new candidate profile also changes how the waiting period is managed. Children referred for transplantation may be very young, sometimes with significant dependence on respiratory or circulatory support. “Hence the growing importance of the ‘bridge to transplant,’” he emphasized.
The use of mechanical support must be considered on a case-by-case basis, depending on the underlying disease, age, potential for recovery, rehabilitation prospects, and the likelihood of quickly obtaining a suitable graft.
Added to these challenges is a structural constraint: finding a graft suited to a child’s size, especially for very young children. The limited number of pediatric donors can lead to prolonged waiting times.
New Recommendations
Pediatric lung transplantation remains a rare procedure. The ISHLT registry recorded 1925 pediatric lung transplants between 1992 and 2024, compared with more than 67,000 in adults. These limited numbers complicate both the evaluation of strategies and the training of specialized teams.
“The ISHLT consensus published in 2025 is an important milestone,” said Benden.
It is the first international document devoted entirely to the guidance and selection of pediatric candidates for lung transplantation, though it still has limitations, including the reinterpretation of historical criteria in light of HEMT for CF, and specific referral and enrollment criteria for PAH and interstitial lung diseases.
This story was translated from Medscape’s French edition.
