Daiva Parakininkas

Increased Mortality After Pulmonary Fungal Infection Within the First Year After Pediatric Lung Transplantation

BACKGROUND Risk factors, morbidity and mortality from pulmonary fungal infections (PFIs) within the first year after pediatric lung transplant have not previously been characterized. METHODS A retrospective, multicenter study from 1988 to 2005 was conducted with institutional approval from the 12 participating centers in North America and Europe. Data were recorded for the first post-transplant year. The log-rank test assessed for the association between PFI and survival. Associations between time to PFI and risk factors were assessed by Cox proportional hazards models. RESULTS Of the 555 subjects transplanted, 58 (10.5%) had 62 proven (Candida, Aspergillus or other) or probable (Aspergillus or other) PFIs within the first year post-transplant. The mean age for PFI subjects was 14.0 years vs 11.4 years for non-PFI subjects (p < 0.01). Candida and Aspergillus species were recovered equally for proven disease. Comparing subjects with PFI (n = 58) vs those without (n = 404), pre-transplant colonization was associated with PFI (hazard ratio [HR] 2.0; 95% CI 0.95 to 4.3, p = 0.067). Cytomegalovirus (CMV) mismatch, tacrolimus-based regimen and age >15 years were associated with PFI (p < 0.05). PFI was associated with any prior rejection higher than Grade A2 (HR 2.1; 95% CI 1.2 to 3.6). Cystic fibrosis, induction therapy, transplant era and type of transplant were not associated with PFI. PFI was independently associated with decreased 12-month survival (HR 3.9, 95% CI 2.2 to 6.8). CONCLUSIONS Risk factors for PFI include Grade A2 rejection, repeated acute rejection, CMV-positive donor, tacrolimus-based regimen and pre-transplant colonization.

Respiratory viral infections within one year after pediatric lung transplant.

Abstract: To characterize epidemiology and risk factors for respiratory viral infections (RVI) in pediatric lung transplant recipients within the first post‐transplant year, a retrospective multicenter study of pediatric lung transplant recipients from 1988 to 2005 was conducted at 14 centers in the United States and Europe. Data were recorded for 1 year post transplant. Associations between RVI and continuous and categorical risk factors were assessed using Wilcoxons rank‐sum and χ2 tests, respectively. Associations between time to RVI and risk factors or survival were assessed by multivariable Cox proportional hazards models. Of 576 subjects, 79 subjects (14%) had 101 RVI in the first year post transplant. Subjects with RVI were younger than those without RVI (median ages 9.7, 13; P<0.01). Viruses detected included adenovirus (n=25), influenza (n=9), respiratory syncytial virus (n=21), parainfluenza virus (n=19), enterovirus (n=4), and rhinovirus (n=22). In a multivariable model for time to first RVI, etiology other than cystic fibrosis (CF), younger age, and no induction therapy were independently associated with risk of RVI. Cytomegalovirus serostatus and acute rejection were not associated with RVI. RVI was independently associated with decreased 12‐month survival (hazard ratio 2.6, 95% confidence interval 1.6–4.4). RVI commonly occurs after pediatric lung transplantation with risk factors including younger age and non‐CF diagnosis. RVI is associated with decreased 1‐year survival.

The risk, prevention, and outcome of cytomegalovirus after pediatric lung transplantation.

Background. A retrospective review of pediatric lung transplant recipients at 14 centers in North America and Europe was conducted to characterize the epidemiology and the risk factors for cytomegalovirus (CMV) and to explore the impact of preventative antiviral therapy. Methods. Data were recorded for 1 year posttransplant. Associations between CMV and continuous and categorical risk factors were assessed using Wilcoxon rank sum and chi-square tests, respectively. Associations between time to CMV and risk factors or survival were assessed by multivariable Cox proportional hazards models. Results. Within 12 months posttransplant, 172 of 577 subjects (29.8%) developed 218 CMV episodes (90 asymptomatic infection, 25 syndrome, and 103 disease). Forty-one subjects developed more than one episode of CMV. Donor or recipient CMV seropositivity was associated with increased risk of CMV episodes. Except for decreased prophylaxis in CMV D−/R− subjects, duration of prophylaxis did not vary by D/R serostatus. For CMV D+ subjects, not being on prophylaxis at the time of CMV episode increased the risk of CMV (D+/R+ hazard ratio 3.5, 95% confidence interval 1.4–8.4; D+/R− 1.9, 1.02–3.7). CMV was associated with increased mortality within the first posttransplant year among those with donor or recipient CMV seropositivity (hazard ratio 2.0: 95% confidence interval 1.1–3.6; P=0.024). Conclusions. CMV remains a serious complication after pediatric lung transplant, and the impact of prophylaxis is complex.

Variability in immunization guidelines in children before and after lung transplantation

Abstract:  Lung transplant candidates and recipients are at high risk of infections from vaccine‐preventable diseases. However, well‐established guidelines neither exist for pre‐ and post‐transplant vaccination nor do monitoring guidelines for pediatric lung transplant recipients. To ascertain the current vaccination and monitoring practices of pediatric lung transplant centers, a self‐administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative in April 2006. Sixteen of 18 centers (89%) surveyed responded. Pretransplant, national vaccination guidelines are followed. Eleven centers reported following standardized vaccination guidelines post‐transplant. Vaccines were more commonly provided by the primary‐care physician pretransplant (69%) rather than post‐transplant (38%). Post‐transplant, 50% of the centers recommend live vaccines for household contacts but not for the transplant recipient. Pretransplant monitoring of response to prior vaccination was performed inconsistently except for varicella (88%). Only 44% of the transplant centers measure for response to vaccination post‐transplant, mostly hepatitis B. Current vaccination practices of pediatric lung transplant centers are heterogeneous. The lung transplant community would be well served by studies designed to evaluate the efficacy of vaccinations in this population.

Cytomegalovirus immunoglobulin decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation.

BACKGROUND Cytomegalovirus (CMV) has been associated with morbidity, including chronic allograft rejection, in transplant recipients. Data from adult centers suggests that CMV hyperimmune globulin (CMVIG) and ganciclovir together are superior in preventing CMV viremia than ganciclovir alone. METHODS A retrospective review of pediatric lung transplant recipients at 14 sites in North America and Europe was conducted to evaluate the effect of adding cytomegalovirus immunoglobulin (CMVIG) prophylaxis to at least 3 weeks of intravenous ganciclovir therapy in pediatric lung transplant recipients. Data were recorded for the first year after transplantation. Associations between time to CMV and risk factors, including CMVIG use, were assessed by multivariable Cox proportional hazards models. RESULTS Of 599 patients whose records were reviewed, 329 received at least 3 weeks of ganciclovir, with 62 (19%) receiving CMVIG. CMVIG was administered more frequently with CMV donor-positive/recipient-negative serostatus (p < 0.05). In multivariable models, patients who did not receive CMVIG as part of their prophylaxis were 3 times more likely to develop CMV infection (hazard ratio, 3.4; 95% confidence interval, 1.2-9.5) independent of CMV serostatus. However, CMVIG administration was not associated with decreased risk of episodes of CMV disease. Receipt of CMVIG was not associated with decreased risks of post-transplant morbidities (acute rejection, respiratory viral infection or early bronchiolitis obliterans) or morbidity within the first year after pediatric lung transplantation. CONCLUSION The use of CMVIG in addition to antiviral prophylaxis in pediatric lung transplantation requires further evaluation.

Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: A multi-center experience†‡

Many children with idiopathic pulmonary arterial hypertension (IPAH) experience disease progression despite advanced medical therapy. In these children, heart‐lung or bilateral lung transplantation (BLTx) remain the only therapeutic options when other treatments fail. Data on functional outcome after BLTx in children with IPAH are limited. We report a multi‐center experience of BLTx for pediatric IPAH.

Minimal acute rejection in pediatric lung transplantation – Does it matter?

Benden C, Faro A, Worley S, Arrigain S, Aurora P, Ballmann M, Boyer D, Conrad C, Eichler I, Elidemir O, Goldfarb S, Mallory GB, Mogayzel PJ, Parakininkas D, Solomon M, Visner G, Sweet SC, Danziger‐Isakov LA. Minimal acute rejection in pediatric lung transplantation – Does it matter?.
Pediatr Transplantation 2010: 14:534–539.

Bilateral lung transplant in Gauchers type-1 disease

Abstract:  We report a case of a patient who received a bilateral lung transplant for end‐stage lung disease secondary to Gauchers type‐1 disease with no evidence of recurrence of the disease in the transplanted lung.

Endoscopic esophageal and tracheal cauterization for closure of recurrent tracheoesophageal fistula: A case report and review of the literature

OBJECTIVE Recurrent tracheoesophageal fistula (TEF) can be a diagnostic and therapeutic challenge. Traditional treatment is thoracotomy, which carries significant morbidity and technical difficulty especially in a previously operated field. Recently, endoscopic techniques have been advocated as a primary approach for treatment of recurrent TEF prior to open repair. This case report describes the endoscopic technique used to address a recurrent TEF. The existing literature of all reported endoscopic cauterization methods is reviewed. METHODS An 8 month old with proximal esophageal atresia and distal TEF underwent endoscopic closure of a recurrent TEF. The fistula was approached endotracheally utilizing Bugbee electrocautery (EC) and endoluminally through the esophagus using argon plasma coagulator and placement of porcine submucosa graft into the tract. Current literature review is presented with a synthesis of data on cases utilizing endoscopically applied EC and the combined results of this closure technique. RESULTS Our patient has maintained successful closure after a single treatment confirmed on follow up endoscopy 6 months post repair. Including this patient, there have been 30 patients with recurrent TEF treated utilizing endoscopic EC reported in the literature. The overall success rate is 78.8% with a mean of 1.88 procedures per successful closure. Comparing EC alone to EC combined with tissue glues or laser, success rates are 67% and 86% respectively. CONCLUSION Endoscopic repair of recurrent TEF has proven to be safe and effective in the literature as an alternative to a second thoracotomy/open surgical repair. EC combined with tissue glues or laser is more effective than EC alone based on available data.