Registry series

The Registry of the International Society for Heart and Lung Transplantation: Thirteenth official pediatric lung and heart-lung transplantation report—2010

Lung transplantation is the definitive surgical treatment for end-stage lung disease. However, infants comprise less than 5% of pediatric cases. This study sought to provide an overview of infant lung transplantation outcomes over the past 3 decades by using linked United Network for Organ Sharing (UNOS) and Pediatric Health Information System (PHIS) data.

Infants undergoing lung transplantation from 1989 to 2020 in UNOS were reviewed. UNOS and PHIS records for patients who underwent lung transplantation from 1995 to 2020 were linked using date of birth, sex, and date of surgery ± 3 days. The study assessed underlying diagnoses, pretransplant and posttransplant extracorporeal membrane oxygenation support, retransplant-free survival to discharge, hospital experience (≥1 annual transplant for ≥4 years in a 5-year period), operative decade, bronchiolitis obliterans syndrome, long-term survival, and functional status at latest follow-up.

A total of 112 lung transplants were performed in 109 infants over 31 years. Of these, 21 patients died before discharge, and 2 underwent repeat transplantation during the same admission. The study linked 80.6% (83 of 103) of UNOS and PHIS records. Hospital survival was lower for infants with idiopathic pulmonary hypertension and those who underwent transplant procedures at less experienced centers. All 7 infants requiring postoperative extracorporeal membrane oxygenation support died. Median freedom from bronchiolitis obliterans syndrome was 8.1 years (interquartile range, 4.6 to 11.6 years). After discharge, median survival was 10.3 years (interquartile range, 6.3 to 14.4 years), with improved 10-year survival for those patients who underwent transplantation from 2010 to 2020 (87.3%) vs 2000 to 2009 (52.4%; P = .098) and 1989 to 1999 (34.1%; P = .004). A total of 84.6% (33 of 39) of survivors had minor or no restrictions at latest follow-up.

Carefully selected infants experience promising short- and long-term outcomes after lung transplantation.

Extracellular vesicles (EVs) play a role in the pathophysiological processes and in different diseases, including cardiovascular disease. Out of several categories of EVs, exosomes (smallest – 30 to 150 nm) are gaining most of the focus as the next generation of biomarkers and in therapeutic strategies. This is because exosomes can be differentiated from other types of EVs based on the expression of tetraspanin molecules on the surface. More importantly, exosomes can be traced back to the cell of origin by identifying the unique cellular marker(s) on the exosomal surface. Recently, several researchs have demonstrated an important and underappreciated mechanism of paracrine cell-cell communication involving exosomal transfer, and its subsequent functional impact on recipient cells. Exosomes are enriched in proteins, mRNAs, miRNAs, and other non-coding RNAs, which can potentially alter myocardial function. Additionally, different stages of tissue damage can also be identified by measuring these bioactive molecules in the circulation. There are several aspects of this new concept still unknown. Therefore, in this review, we have summarized the knowledge we have so far and highlighted the potential of this novel concept of next generation biomarkers and therapeutic intervention.

Donor-specific antibodies (DSA) are integral to the development of antibody-mediated rejection (AMR). Chronic AMR is associated with high mortality and an increased risk for cardiac allograft vasculopathy (CAV). Anti-donor HLA antibodies are present in 3–11% of patients at the time of heart transplantation (HTx), with de novo DSA (predominantly anti-HLA class II) developing post-transplant in 10–30% of patients. DSA are associated with lower graft and patient survival after HTx, with one study suggesting a three-fold increase in mortality in patients who develop de novo DSA (dnDSA). DSA against anti-HLA class II, notably DQ, are at particularly high risk for graft loss. Although detection of DSA is not a criterion for pathologic diagnosis of AMR, circulating DSA are found in almost all cases of AMR. MFI thresholds of ~5000 for DSA against class I antibodies, 2000 against class II antibodies, or an overall cut-off of 5−6000 for any DSA, have been suggested as being predictive for AMR. There is no firm consensus on pre-transplant strategies to treat HLA antibodies, or for the elimination of antibodies after diagnosis of AMR. Minimizing the risk of dnDSA is rational but data on risk factors in HTx are limited. The effect of different immunosuppressive regimens is largely unexplored in HTx, but studies in kidney transplantation emphasize the importance of adherence and maintaining adequate immunosuppression. One study has suggested a reduced risk for dnDSA with rabbit antithymocyte globulin induction. Management of DSA pre- and post-HTx varies but typically most centers rely on a plasmapheresis or immunoadsorption, with or without rituximab and/or intravenous immunoglobulin. Based on the literature and a multi-center survey, an algorithm for a suggested surveillance and therapeutic strategy is provided.

Orthotopic heart transplantation is a well-established and effective therapeutic option for children with end-stage heart failure. Multiple modalities, including noninvasive cardiac imaging, cardiac catheterization, angiography, and endomyocardial biopsy, are helpful to monitor these patients for graft dysfunction, rejection, and vasculopathy. Because of morbidities associated with invasive monitoring, noninvasive imaging plays a key role in the surveillance and evaluation of symptoms in pediatric transplant recipients. Echocardiography with or without stress augmentation may provide serial data on systolic and diastolic function, ventricular deformation, and tissue characteristics in children after transplantation. Although not perfectly sensitive or specific, advanced two- and three-dimensional echocardiographic detection of functional changes in cardiac grafts may allow early recognition of allograft rejection. Magnetic resonance imaging has shown promise for characterization of edema and scar and myocardial perfusion reserve, as well as potential application for the detection of microvasculopathic changes in the transplanted heart. Cardiac computed tomography is particularly well suited for the demonstration of coronary artery dimensions and anatomic residual lesions. In combination, these noninvasive imaging techniques help the transplantation cardiologist screen for graft dysfunction, detect critical graft events, and identify situations that require invasive testing of the transplanted heart. Advanced multimodality imaging techniques are likely to increasingly shape the monitoring practices for children following heart transplantation.

Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS.

From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV₁) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy.

Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV₁ range after treatment between −6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence.

ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.