M.G. Schecter

Is lung transplantation survival better in infants? Analysis of over 80 infants

BACKGROUND There have been >1,600 pediatric lung transplantations (LTx) performed worldwide with a trend toward improved outcomes over the last 25 years. The majority of these LTxs have been in older children and adolescents. Less than 4 infant (defined as ≤ 12 months of age) LTxs per year have been performed over the past 20 years, mostly in the USA. However, infant LTx outcomes have not been well documented in a multi-institutional longitudinal fashion. METHODS The United Network of Organ Sharing database was queried from October 1987 to July 2011. Of the 1,003 pediatric LTxs reported, 84 (8%) were infants. All combined transplantations were excluded. RESULTS Eighty-one infants received 84 LTxs, of which 95% had a bilateral LTx. Median age and weight at LTx was 4 months (range 0 to 11 months) and 5.3 kg (2.7 to 11.8 kg), respectively. Median ischemic time was 5.2 hours (2.0 to 10.8 hours). Overall Kaplan-Meier graft survival was similar for infants compared with other pediatric age group (OPA: >1 to 18 years) LTx recipients (half-life 4.0 years vs 3.4 years, p = 0.7). Conditional 1-year graft survival for infants was significantly higher than OPA (half-life 7.4 years vs 5.0 years, p = 0.024). Early (1987 to 2000, n = 46) and late (2001 to 2011, n = 38) era graft survival was not significantly different. Graft survival in pre-LTx ventilated infants was significantly better than pre-LTx ventilated OPA (half-life 6.1 years vs 0.9 year, p = 0.004) and was not statistically different from pre-LTx infants not on ventilatory support (half-life 6.1 years vs 2.2 years, p = 0.152). Cox regression of 5 variables (weight, donor arterial PO(2), pre-Tx ventilator, organ ischemic time, center experience) showed that survival was associated with increased center experience (p = 0.03). CONCLUSION Infants undergoing LTx have outcomes similar to those of all other pediatric LTx patients.

Long-term impact of respiratory viral infection after pediatric lung transplantation

Liu M, Mallory GB, Schecter MG, Worley S, Arrigain S, Robertson J, Elidemir O, Danziger‐Isakov LA. Long‐term impact of respiratory viral infection after pediatric lung transplantation. 
Pediatr Transplantation 2010: 14:431–436.

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.

Lung transplantation for childhood diffuse lung disease.

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.

Hypogammaglobulinemia: Incidence, risk factors, and outcomes following pediatric lung transplantation

Abstract:  Infection is the leading cause of morbidity and mortality in the first year following lung transplantation. HG after adult lung transplantation has been associated with increased infections and hospitalization as well as decreased survival. The purpose of this study is to define the incidence, risk factors, and outcomes of HG in the first year following pediatric lung transplantation. A retrospective review of all lung transplant recipients at a single pediatric center over a four‐yr period was performed. All serum Ig levels drawn within one yr of transplantation were recorded. An association between HG during the first year after transplantation and age, race, gender, diagnosis leading to transplantation and clinical outcomes including hospitalization, infections requiring hospitalization, viremia, fungal recovery from BAL lavage, and mortality was sought. HG was defined using age‐based norms. Fifty‐one charts were reviewed. Mean (±s.d.) post‐transplantation levels for IgG, IgA, and IgM were 439.9 ± 201.3, 82.3 ± 50.2, and 75.2 ± 41.4 mg/dL, respectively. HG was present in 48.8%, 12.2%, and 17.1% of patients for IgG, IgA, and IgM, respectively. Patients with HG for IgG were older (14.3 ± 3.8 vs. 9.2 ± 5.4 yr; p < 0.01). IgA and IgM HG were associated with invasive aspergillosis (p < 0.01 and p = 0.05, respectively). IgG and IgM levels inversely correlated with bacterial infections and hospital days, respectively (p < 0.01, p < 0.05). HG is a frequent complication following pediatric lung transplantation. Low Ig levels are associated with increased infections and hospital stay.

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.

Clostridium difficile colitis in children following lung transplantation

Rosen JB, Schecter MG, Heinle JS, McKenzie ED, Morales DL, Dishop MK, Danziger‐Isakov L, Mallory GB, Elidemir O. Clostridium difficile colitis in children following lung transplantation.
Pediatr Transplantation 2010: 14:651–656.

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. Pediatr Pulmonol. 2009; 44:536–546.

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

Abstract:  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.

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.