Surgical Considerations in Infant Lung Transplantation

Challenges and Opportunities

John P. Costello; Horacio G. Carvajal; Aaron M. Abarbanell; Pirooz Eghtesady; Dilip S. Nath

Disclosures

American Journal of Transplantation. 2021;21(1):15-20. 

In This Article

Postoperative Outcomes and Discussion

Khan and Morales performed the first large multi-institutional review of pediatric lung transplant outcomes utilizing the UNOS database, with specific focus placed on evaluating outcome differences between infants and pediatric recipients over 1 year of age.[1] Between 1987 and 2011, a total of 1003 isolated lung transplants were performed in pediatric patients, with 84 performed in infants. Unfortunately, information about the specific surgical technique of lung transplantation utilized in these patients was not reported, as it is not currently captured in the UNOS database. Although 1-year graft survival in infants was significantly higher than in the older patient group, there was no difference in overall graft survival. Notably, 104 separate institutions performed transplants in children over 1 year of age, whereas only 10 centers performed lung transplants in infants over this entire 24-year period. In addition, in the 5 years leading up to 2012, only two centers performed infant lung transplants, highlighting the fact that experience with this procedure in infants has historically been limited to a select few institutions.[1]

The largest single institution series of infant and pediatric lung transplants to date was reported by Elizur et al at SLCH in 2009, consisting of 292 transplants performed between 1990 and 2004.[6] Of these, 226 were isolated lung transplants. Over this period, 36 transplants were performed in infants. Toddlers between the ages of 1 and 3 years accounted for an additional 26 isolated lung transplants. There was no significant difference in 1- and 3-year survival rates between these two groups; likewise, these survival rates did not differ for infants when compared to children over the age of 3. These data echo contemporaneous findings from the 2007 ISHLT registry report.[28] In all three groups, the leading cause of mortality was bronchiolitis obliterans syndrome at over 30%, although the burden of this condition was much higher in children over 3 years of age, accounting for 52% of all mortalities. Consistent with earlier data on the risk of acute rejection based on age at transplantation,[29] infants and toddlers in this study had significantly decreased rates of acute rejection at 1 and 3 years posttransplant compared to children transplanted over the age of 3 years.[6] Moreover, significantly more infants and toddlers had no episodes of acute rejection at any point during follow-up compared to older children. Comparison between infants and children transplanted due to genetic surfactant disorders also showed lower rates of bronchiolitis obliterans among infants, indicating that the observed difference is not due to the underlying pathology.[17] Rather, these outcomes may be explained by the immunologic tolerance that neonates and young infants appear to exhibit in all different forms of solid organ transplantation. It is well described that infants develop B cell tolerance in the setting of ABO-incompatible transplantation, which may partly account for the lower levels of immunosuppression required for this age group.[30] Taken together, these data highlight that infant lung transplant recipients have rejection and survival outcomes that are comparable and possibly even superior to those of their older pediatric counterparts.

Despite the relative scarcity of data on infant lung transplantation compared to older children, there are a number of salient points regarding outcomes of each surgical technique. In the case of Elizur et al,[6] all bilateral lung transplants performed in infants employed the bilateral sequential technique. Although the bronchial anastomoses were wrapped with donor and recipient peribronchial tissue, no BAR was performed.[31] This certainly raises the question of whether their outcomes would have differed if an en bloc technique had been utilized in these patients. To answer this question, Guzman-Pruneda et al compared outcomes between 88 children with bilateral sequential lung transplants and 31 children with en bloc transplants with BAR.[20] This series, analyzing outcomes for pediatric lung transplants performed at a single institution between 2005 and 2014, comprises the largest such analysis. Although infants were included (with the youngest patient being two months of age), the authors do not mention how many of the 119 patients were infants or toddlers, and outcomes were not compared between age groups. Nevertheless, when looking at the entire cohort in aggregate, several important findings were identified. On both univariate and multivariate analyses, en bloc lung transplantation with BAR had significantly lower rates of airway ischemia/injury findings, although not airway re-interventions, compared with the bilateral sequential transplantation technique. Freedom from bronchiolitis obliterans syndrome was higher (94% vs 71%) following utilization of the en bloc with BAR technique, although this difference was not statistically significant. This is particularly important in infants and children given their lower rates of acute rejection and contemplating that even a single episode of acute rejection is known to increase the risk for chronic allograft dysfunction.[3] As such, the possible combination of lower rates of bronchiolitis obliterans syndrome achieved through en bloc transplantation with BAR and the lower rate of acute rejection seen in infants and young children need further study.

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