Developing an adolescent and adult Fontan Management Programme.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Heart-Lung Transplant via an Eighth-Time Sternotomy.

We report a combined heart-lung transplantation following seven prior sternotomies in a patient born with a transitional atrioventricular septal defect. Previous surgeries to repair and replace the mitral valve led to pulmonary vein stenosis and pulmonary vascular disease. Eighth-time sternotomy and significant vascular adhesions led to a prolonged operation and to placing the heart-lung block anterior to the phrenic nerves. Despite this, the patient was ready for discharge after two weeks and continues to do well over nine months later. As more patients survive multiple cardiac palliations with some developing pulmonary vascular disease, heart-lung transplantation may become relevant again.

Pediatric trichodysplasia spinulosa: A report of 2 cases and review of the literature.

Trichodysplasia spinulosa is a rare disorder caused by the ubiquitous trichodysplasia spinulosa-associated polyomavirus (TSPyV) and characterized clinically by predominately centrofacial, but often generalized, folliculocentric papules with protuberant keratinaceous spines. Although seroprevalence reaches up to 70% in adult populations, TSPyV causes clinical manifestations in a small percentage of patients who are immunosuppressed. Diagnosis can be made using typical clinical and histologic features, SV40T antibody immunostaining, and PCR of various tissues including the keratinaceous spine, skin, serum, urine, and CSF. Various topical and systemic medications have demonstrated variable success. Decreasing or discontinuing immunosuppression has also been shown to improve or alleviate clinical manifestations.

Bronchial artery revascularization and en bloc lung transplant in children.

BACKGROUND: Long-term success in pediatric lung transplantation is limited by infection and bronchiolitis obliterans syndrome (BOS). The bilateral sequential lung transplantation (BSLT) technique may result in airway ischemia leading to bronchial stenosis, dehiscence, or loss of small airways. En bloc lung transplant (EBLT) with bronchial artery revascularization (BAR) minimizes airway ischemia, thus promoting superior airway healing. BAR also allows for safe tracheal anastomosis, circumventing the need for bilateral bronchial anastomoses in small children. METHODS: This was a retrospective review of bilateral transplantations from 2005 to 2014. Both techniques were used in parallel. Redo and multiorgan transplants were excluded. RESULTS: There were 119 recipients comprising 88 BSLTs and 31 EBLTs. Follow-up time was 3 years (interquartile range, 1-5 years). Donor ischemic and cardiopulmonary bypass times were not different between techniques (p = 0.48 and p = 0.18, respectively). Degree of graft dysfunction and cellular rejection scores were not different (p = 0.83 and p = 0.93, respectively). There were 3 hospital deaths after BSLT and 2 after EBLT (p = 0.60). Overall survival was 61% for the BSLT group and 77% for the EBLT group (p = 0.54). Freedom from BOS was 71% in the BSLT group and 94% in the EBLT group (p = 0.08). On routine bronchoscopy, 57% BSLT and 16% EBLT patients had 1 or more airway ischemic findings (p < 0.0001). Multivariate analysis showed BSLT was associated with higher ischemic injury (relative risk, 2.86; 95 confidence interval, 1.3-6.5; p = 0.01) and non-airway complications (relative risk, 4.62; 95% confidence interval, 1.1-20.2; p = 0.04) but not airway reinterventions (p = 0.07). Airway dehiscence occurred in 3 BSLT patients. CONCLUSIONS: Pediatric EBLT with BAR can be safely performed without increasing operative or graft ischemic times. Airway ischemia and non-airway complications were significantly reduced when BAR was combined with tracheal anastomosis, potentially diminishing morbidity caused by anastomotic healing complications.

Changes in body composition after lung transplantation in children.

BACKGROUND: The evaluation of nutritional status, including body composition measurements, in pediatric patients before and after lung transplant (LTx) can aid in adapting nutrition support and physical rehabilitation programs to meet individual patient needs. The purpose of this retrospective study was to determine the changes in weight, lean body mass (LBM), and body fat (BF) before and after LTx and their association with lung function in pediatric patients. METHODS: Included were 41 LTx patients, aged 3 months to 20.7 years, who had at least 2 body composition measurements determined by dual-energy X-ray absorptiometry (GE Lunar Prodigy, Waukesha, WI) in the first 2 years after LTx were measured pre-LTX and at 12 or 24 months post-LTX, for weight, LBM, and BF. RESULTS: Pre-LTx, 29% of patients had moderate and 12% had severe chronic malnutrition (growth stunting). This compares with 21% of patients being moderately LBM-depleted and 23% being BF-depleted. The weight change at 12 and 24 months was +9.3% (interquartile range, 5.6%-23%) and +4.7% (0.9%-11.6%), respectively; whereas the LBM change at 12 and 24 months was +15.2% (6.8%-17.1%) and +4.2% (-0.6% to 7.7%), respectively. LBM percentiles correlated with pulmonary function tests ( % predicted forced vital capacity [ρ = 0.36, p = 0.001] and forced expiratory volume in 1 second [ρ = 0.265, p = 0.015). CONCLUSIONS: Maximum weight and LBM gain occur at 12 months after LTx, with smaller gains noted at 24 months. Clinicians must look beyond height and weight and evaluate LBM and fat mass in pediatric patients after LTx.

Lung transplantation for childhood diffuse lung disease.

BACKGROUND: Pediatric diffuse lung diseases comprise a heterogeneous group of rare lung disorders which may lead to end stage lung disease and referral for lung transplantation. Previous studies are limited by small numbers of patients with specific forms of diffuse lung disease. Children with all forms of diffuse lung disease who underwent lung transplantation at two pediatric centers were evaluated in terms of several pre- and post-transplant factors and compared to children with other end stage lung disorders. METHODS: A retrospective chart review was performed on all patients transplanted between October 1, 2002 and June 15, 2007 at Texas Children's Hospital and St. Louis Children's Hospital. Multiple pre-transplant characteristics and post-transplant morbidities and mortality were compared between diffuse lung disease, cystic fibrosis, and pulmonary vascular disease groups. RESULTS: There were 31 diffuse lung disease (DLD), 57 cystic fibrosis (CF), and 16 pulmonary vascular disease (PVD) patients included in our analysis. Patients with DLD had significantly higher pre-transplant morbidity including lower percent predicted of forced expiratory volume in first second (P = 0.013) and more patients with pulmonary hypertension (P = 0.001) and hypercapnia (P = 0.031). Compared to CF patients, more DLD and PVD patients required invasive ventilation (P = 0.001) and care in the pediatric intensive care unit (P = 0.001). After transplant, there was a difference among the three groups with regards to number of acute allograft rejections but statistical limitations preclude knowing between which group the difference lies. A difference in time to bronchiolitis obliterans was found between the PVD and CF groups but not when compared to the DLD patients. The three groups had similar time to post-transplant lymphoproliferative disease, rate of infections, and survival. CONCLUSION: Lung transplantation is as successful for patients with end stage diffuse lung disease as compared to other lung transplant candidates.

Does donor arterial partial pressure of oxygen affect outcomes after lung transplantation? A review of more than 12,000 lung transplants.

INTRODUCTION: In lung transplantation (LTx), the arterial partial pressure of oxygen (PaO(2)) is traditionally regarded as critical information for assessment of donor lung function. Each center sets its own thresholds; by convention, a donor PaO(2) of less than 300 mm Hg has been considered disqualifying. Limited literature exists to support such a practice. We analyzed all LTxs performed in the United States over a 9-year period to assess the effect of donor PaO(2) on graft survival. METHODS: The United Network for Organ Sharing (UNOS) database was queried for LTx (January 2000-November 2009). Of 12,545 LTx performed, 12,045 (96%) had donor PaO(2) data on a fraction of inspired oxygen of 1.0, recorded at the time of procurement. RESULTS: Mean donor PaO(2) was 407 ± 140 mm Hg. The majority of LTxs had a donor PaO(2) greater than 300 mm Hg (9593 (80%]) whereas PaO(2) was 200 mm Hg or less in 1830 (15%) and 201 to 300 in 582 (5%) donors. Use of donors with a PaO(2) of less than 200 increased over time from 5% (45) in 2000 to 21% (295) in 2009 (P = .002). Kaplan-Meier survival analysis showed no difference in graft survival with differing donor PaO(2)s, irrespective of whether patients had a single or double LTx. A Cox multivariable analysis of 21 donor characteristics demonstrated that donor PaO(2) had no association with graft survival. CONCLUSIONS: Donor PaO(2) levels did not affect graft survival. The use of donors with lower PaO(2)s could substantially increase the donor pool. We are not suggesting that donor PaO(2) is not important when assessing potential lung donors but its level of importance in regard to other criteria appears less than previously believed.

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

OBJECTIVE: Since 1988, approximately 1100 pediatric lung transplants have been performed worldwide with consistent improvement in survival. Similarly, survival for pediatric heart transplant has increased over the years; however, in this cohort improvement in survival is exclusively a result of increased early (1-year) survival. To observe if this same phenomenon exists in pediatric lung transplants, the United Network for Organ Sharing database was analyzed to evaluate and characterize how pediatric lung transplant survival has changed in the past 2 decades. METHODS: The United Network for Organ Sharing database was queried for patients aged 18 years or less who underwent lung transplantation from May 1988 to May 2008. Analysis included 959 pediatric lung transplants. RESULTS: Age groups were infants (≤1 years) (n = 106 [11%]), children (2-12 years) (n = 299 [31%]), and adolescents (≥13 years) (n = 554 [58%]). A total of 546 (57%) were girls. Kaplan-Meier survival was significantly better in the late era (2002-2008) than in all other eras (1988-1994 and 1995-2001) (P < .05). The half-life for graft has increased significantly over the eras (early, 2.2 years; mid, 3.3 years; and late, 3.8 years). Conditional 1-year survival (ie, mid to late survival) was not significantly different (P = .3) among the eras. Gender, age, diagnosis, prolonged ischemic time, and cytomegalovirus mismatch did not significantly affect overall patient or graft survival. Chronic preoperative steroid dependence (P = .02), preoperative ventilatory dependence (P < .001), and retransplantation (P = .02) were associated with decreased survival. CONCLUSIONS: Survival in pediatric lung transplant has increased significantly over the years, but this improvement primarily reflects improvement in early survival. Survival in pediatric lung transplant after the first posttransplant year has not changed in more than 2 decades.

Lung retransplantation in children: appropriate when selectively applied.

BACKGROUND: Lung retransplantation (re-LTx) in children has been associated with lower survival rates compared with primary lung transplantation. However, improving survival for primary LTx has led to more patients presenting for re-LTx. Therefore, an analysis of the UNOS (United Network of Organ Sharing) database to evaluate the effectiveness of pediatric lung retransplantation in the United States was completed. METHODS: The UNOS registry was queried for pediatric re-LTx patients from May 1988 to May 2008. There were 81 (10%) re-LTx out of a total 802 pediatric lung transplants. RESULTS: Median age and weight at re-LTx were 14 (range, 0 to 18) years and 32 (4 to 58) kg. Indications for re-LTx were obliterative bronchiolitis in 50 patients (62%), primary graft failure in 8 (10%), and other in 23 (28%). The Kaplan-Meier graft survival for re-LTx patients was worse than for primary transplant patients (p < 0.001, graft half-life 0.9 vs 4.0 years), especially if re-LTx was done less than 1 year after primary transplant (graft half-life 0.25 years). Graft survival in patients who underwent re-LTx greater than 1 year after primary transplant was not statistically different than for primary LTx patients (p = 0.21; graft half-life 2.8 vs 4.0 years), and if re-LTx greater than 1 year posttransplant occurred in patients who were not ventilator dependent, survival was further improved (p = 0.68; graft half-life 4.7 vs 4.0 years). CONCLUSIONS: Pediatric lung retransplantation within the first year after primary transplant does not appear advisable. Pediatric re-LTx greater than 1 year after primary transplantation may be a reasonable strategy for end-stage graft failure. Patients greater than 1 year posttransplant and not ventilator dependent appear an even more compelling group in which to consider lung retransplantation.

Fungal infections in pediatric lung transplant recipients: colonization and invasive disease.

BACKGROUND: The purpose of this study was to evaluate the epidemiology and investigate the impact of colonization and pulmonary fungal infections (PFIs). METHODS: In this investigation we performed a retrospective analysis of 55 pediatric lung transplant recipients from 2002 to 2007 at a single institution. Associations between risk factors and time to post-transplant colonization, PFI, and other outcomes were assessed using Cox proportional hazard models. RESULTS: Although 29 patients had positive pre-transplant colonization, 33 (60%) were colonized post-transplant and 20% (11 subjects) developed proven or probable PFI. In a multivariate model, post-transplant fungal colonization was associated with older age (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1 to 7.6), cytomegalovirus (CMV) prophylaxis (HR 5.6, 95% CI 1.3 to 24.6) and respiratory viral infection prior to fungal colonization (HR 2.9, 95% CI 1.0 to 8.3). CONCLUSION: Neither fungal colonization nor PFI was associated with the development of chronic allograft rejection or death.

Management of the pediatric organ donor to optimize lung donation.

Lung transplantation in childhood is a highly specialized clinical practice confined to a few centers around the world. Organ availability remains an important limiting factor in extending the application of this procedure to more infants, children and adolescents. The lungs are the organ most vulnerable to injury, infection and dysfunction among transplantable organs in the brain dead deceased donor. In this manuscript, we review the pathophysiology of the most common and important disease states that affect the lungs in potential donors. Furthermore, we herein provide recommendations for optimal management of the pediatric organ donor with an emphasis on strategies to improve the opportunity for the lungs to be placed in candidates on the transplant list.

Post-transplant lymphoproliferative disease in pediatric lung transplant recipients: recent advances in monitoring.

To investigate the clinical validity of newer diagnostic tests such as monitoring of EBVqPCR and lymphocyte function assay ImmuKnow in helping to diagnose PTLD in pediatric lung transplant recipients. Single-center, retrospective case-control study. CsA trough levels, EBVqPCR and ImmuKnow (Cyclex Inc., Columbia, MD, USA) levels were measured serially as part of routine care. Re-transplant patients and patients who did not reach 12 months post-transplant at the time of analysis were excluded. Twenty-seven patients met the inclusion criteria. The study group consisted of seven patients who developed PTLD, five of which were EBV- recipients who received EBV+ lungs. The rest of the eligible patients served as controls. Median time to develop PTLD was 273 days (range: 166-343). One, two, three, six, and nine months after transplant, mean (+/-s.d.) CsA trough whole blood levels (ng/mL) were not different between the two groups: 378 +/- 38, 390 +/- 52, 402 +/- 89, 359 +/- 42, and 342 +/- 115, vs. 416 +/- 105, 347 +/- 64, 337 +/- 78, 333 +/- 86, and 281 +/- 54 [PTLD vs. no-PTLD, respectively (p > 0.05 for all time points)]. Mean (+/-s.d.) EBVqPCR levels (copies/mL) measured at three, six, and nine months post-transplant were significantly elevated in PTLD group compared to no-PTLD group: 84 +/- 99, 3384 +/- 7428 and 839 +/- 1444 vs. 9 +/- 26, 8 +/- 36 and 32 +/- 136, respectively (p < 0.05 for all time points). Mean (+/-s.d.) ImmuKnow levels (ATP ng/mL) at three, six, and nine months post-transplant were significantly lower in the PTLD group when compared with no-PTLD group: 144 +/- 67, 137 +/- 110, and 120 +/- 153 vs. 290 +/- 161, 300 +/- 162, and 293 +/- 190, respectively (p < 0.05 for all time points). Close monitoring of EBV viral load by qPCR and the degree of immunosuppression via ImmuKnow may guide physicians to reach the diagnosis of PTLD early.

Pediatric lung transplantation: a therapy in its adolescence.

Pediatric lung transplant was born at the University of Toronto as an extension of the pioneering work of Cooper and Patterson in adult lung transplant in the 1980s. Through the 1990s, the field of pediatric lung transplantation grew with clinical outcomes in the largest centers being comparable to those in adult lung transplantation. For children and adults, the largest obstacle to long-term survival remains chronic allograft rejection secondary to the development of bronchiolitis obliterans, for which little advancement has been made in prevention or treatment. While transplantation has become accepted therapy for end-stage lung disease in adults, pediatric lung transplant has been less widely embraced for multiple reasons, such as adolescent non-compliance and the investment required in developing freestanding pediatric lung transplant centers. Another factor limiting pediatric lung transplant has been the paucity of suitable donor lungs. In 2002, Texas Children's Hospital and the Baylor College of Medicine successfully collaborated in developing an active and successful pediatric lung transplant program. Through our own work and an international collaborative of pediatric transplant pulmonologists and surgeons, we are hoping to move the field of pediatric lung transplant out of its "adolescence" into adulthood.

BK virus-associated hemorrhagic cystitis in a pediatric lung transplant recipient.

BKV was first postulated to be a potential pathogen in 1971 when it was isolated in the urine of a renal transplant recipient. The pathology of BKV is generally confined to the urinary tract. In renal transplant recipients, BKV has been associated with hemorrhagic cystitis, urethral stenosis, and interstitial nephritis. Reports of BKV infection in lung transplant recipients are limited to a few case reports in adult patients. A recent report revealed that up to 32% of adult lung transplant recipients may shed BKV in their urine without symptoms or renal dysfunction. To our knowledge, there are no published reports of pediatric lung transplant recipients with BKV-associated hematuria. We hereby report a case of BKV-induced hemorrhagic cystitis in a pediatric lung transplant recipient.

Treatment of adenovirus pneumonia with cidofovir in pediatric lung transplant recipients.

BACKGROUND: Adenovirus pneumonia results in significant morbidity and mortality in lung transplant recipients. Cidofovir allows for directed therapy but can result in nephrotoxicity. We report our experience with cidofovir for the treatment of adenovirus pneumonia in pediatric lung transplant recipients. METHODS: In a retrospective review, we identified four cases of culture-proven adenovirus pneumonia in children who underwent lung transplantation at Texas Children's Hospital (TCH). All patients received cidofovir 1 mg/kg every other day or three times a week for a total of 4 weeks. Probenecid and intravenous hydration were administered in conjunction with the cidofovir. Intravenous immunoglobulin (IVIg) was given as adjunctive therapy, and immunosuppression was not modified during the treatment course. RESULTS: The four cases of adenovirus pneumonia comprised 4 of the 54 (7%) lung transplantations performed at TCH from 2002 to 2006, and all were in children <3 years of age. All patients developed pneumonia within 2 months after transplantation. With cidofovir treatment, three of the four children survived. Among the survivors, two developed early bronchiolitis obliterans within 1 year after transplant, and one has continued to have good graft function at 2 years after transplant. All patients maintained normal renal function throughout the treatment course. CONCLUSIONS: Pediatric lung transplant recipients <3 years of age are at increased risk of adenovirus pneumonia early after transplantation. Cidofovir, when used in the modified dosing regimen and in combination with IVIg and renal protection measures, is a safe and potentially effective treatment option for adenovirus pneumonia in lung transplant recipients.