Pediatric Lung Transplantation Research Articles

Flexible bronchoscopy in pediatric lung transplantation.

Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field.

A novel approach to reducing hepatotoxicity related to fungal prophylaxis in pediatric lung transplant recipients.

Pediatric lung transplant patients are at risk for developing invasive fungal infections post-transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first-line agent, has been shown to cause hepatotoxicity. We describe a single-center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post-transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post-operative course. This is a retrospective review of patients in the age 0-18 who received a lung transplant from June 2016-May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results. Forty-two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post-operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post-transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post-transplant, but this difference was not found to be statistically significant (p = .507). An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post-lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post-lung transplant are warranted.

Anesthesia for lung transplantation in children under 12 years of age: a single center experience of China

PurposeThis study aims to provide a comprehensive overview of anesthesia management strategies employed in pediatric lung transplantation.MethodsA retrospective analysis was conducted on data from 14 pediatric patients who underwent lung transplantation at the Wuxi Center between September 2019 and November 2022. Patient demographics, surgical particulars, airway management, utilization of extracorporeal support, fluid administration, blood gas and electrolyte profiles, and postoperative outcomes were systematically documented and subsequently summarized.ResultsOf the 14 patients, 7 received extracorporeal membrane oxygenation (ECMO) and 1 received cardiopulmonary bypass (CPB). The average operation time was 303 ± 53 min, with the median extubation time of 26 h. The entirety of pediatric lung transplant procedures was executed successfully, resulting in the discharge of thirteen patients postoperatively. Regrettably, one patient died due to infectious shock on the fourth postoperative day.ConclusionThe achievement of successful pediatric lung transplantation necessitates effective perioperative anesthesia management, with a focal emphasis on circulatory control. Real-time measurements serve as the cornerstone for decision-making. Proactive administration of vasoactive agents is integral to sustaining hemodynamic stability. The judicious assessment of ECMO necessity is paramount, favoring central ECMO during the surgical intervention.

Pediatric Lung Transplantations: New Possibilities and Challenges in Treatment of Children With End-Stage Respiratory Failure

Lung transplantation (LTx) is the last treatment option for children with end-stage respiratory failure. According to the literature, cystic fibrosis remains the most common cause of pediatric LTx. The study aimed to assess the characteristics of pediatric LTx recipients as well as the outcomes of the transplantation. Our study is a single-center retrospective review of clinical data of all 11 patients who underwent a LTx before the age of 18 years between the years 2016 and 2020. Medical records were examined for patients' characteristics, general treatment, and complications. There were a total of 11 patients (8 males) with a median age 14.5 years (range: 11-17). The primary diseases that led to LTx were: cystic fibrosis in 8 patients (72.73%), hereditary hemorrhagic telangiectasia in 2 patients (18.18%), and idiopathic pulmonary arterial hypertension in 1 patient (9.09%). Median period from qualification to LTx was 235.55 days (range: 11-748). Two patients (18.18%) underwent lung retransplantation after 3 and 5 years. One patient passed away 10 months after surgery due to noncompliance. Pediatric lung transplantation is less common than lung transplantation in adults. It also differs in fields of donors accessibility, stronger immune system response and noncompliance that may lead to graft failure.

(1359) - Trends in Pediatric Lung Transplantation Following the Height of the COVID-19 Pandemic

(1359) - Trends in Pediatric Lung Transplantation Following the Height of the COVID-19 Pandemic

(1360) - Paediatric Lung Transplantation for Childhood Interstitial Lung Disease Shows Favorable Outcome Compared with LuTx for Cystic Fibrosis or Pulmonary Hypertension

(1360) - Paediatric Lung Transplantation for Childhood Interstitial Lung Disease Shows Favorable Outcome Compared with LuTx for Cystic Fibrosis or Pulmonary Hypertension

(209) - Outcomes in Donation After Circulatory Death Pediatric Lung Transplants: An Analysis of the ISHLT Registry

(209) - Outcomes in Donation After Circulatory Death Pediatric Lung Transplants: An Analysis of the ISHLT Registry

Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.

The appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels. The present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels. Within normal hematocrit levels, for children with lung transplantation who do not carry the CYP3A5*1 gene and have no coadministration with voriconazole, it is recommended to administer tacrolimus at a dosage of 0.02 mg/kg/day, divided into two doses, for children weighing 10-32 kg, and a dosage of 0.03 mg/kg/day, also divided into two doses, for children weighing 32-40 kg. For children with lung transplantation who carry the CYP3A5*1 gene and have no coadministration with voriconazole, tacrolimus dosages of 0.02, 0.03, and 0.04 mg/kg/day split into two doses are recommended for children weighing 10-15, 15-32, and 32-40 kg, respectively. For children with lung transplantation who do not carry the CYP3A5*1 gene and have coadministration with voriconazole, tacrolimus dosages of 0.01 and 0.02 mg/kg/day split into two doses are recommended for children weighing 10-17 and 17-40 kg, respectively. For children with lung transplantation who carry the CYP3A5*1 gene and have coadministration with voriconazole, a tacrolimus dosage of 0.02 mg/kg/day split into two doses is recommended for children weighing 10-40 kg. It is the first time to optimize the initial dosage of tacrolimus in Chinese children undergoing lung transplantation within normal hematocrit.

Gastrointestinal complications in pediatric lung transplant recipients: Incidence, risk factors, and effects on patient outcomes.

Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post-operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients. We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post-transplant period. Lastly, we investigated the association of these complications with mortality and graft survival. 84.3% of lung transplant recipients experienced at least one GI complication in the post-transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post-operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p = .021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p = .027). Exposure to opioids in the post-operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes.

Lung transplantation in children.

Lung transplantation is a well-established treatment for children facing advanced lung disease and pulmonary vascular disorders. However, organ shortage remains highest in children. For fitting the small chest of children, transplantation of downsized adult lungs, lobes, or even segments were successfully established. The worldwide median survival after pediatric lung transplantation is currently 5.7 years, while under consideration of age, underlying disease, and peri- and posttransplant center experience, median survival of more than 10 years is reported. Timing of referral for transplantation, ischemia-reperfusion injury, primary graft dysfunction, and acute and chronic rejection after transplantation remain the main challenges.

Interstitial lung disease as an indication for pediatric lung transplant.

Interstitial lung disease can be an indication for lung transplant at any age, but it is a particularly common indication for lung transplant in infants. Nevertheless, not all interstitial lung diseases will lead to lung transplant in childhood. Genetic testing has aided the identification of these diseases in children. In severely affected patients, however, definitive diagnosis is not always necessary to consider referral to a transplant center. At experienced transplant centers, a multidisciplinary team educates patient families and aids in the transplant evaluation of children with interstitial lung disease. Children who have undergone transplant require lifetime immunosuppression and close surveillance, but can enjoy good quality of life for years following surgery.

Disparities in lung transplantation in children.

Lung transplantation is a recognized therapy for end-stage respiratory failure in children and young people. It is only available in selected countries and is limited by access to suitable organs. Data on disparities in access and outcomes for children undergoing lung transplantation are limited. It is clear from data from studies in adults, and from studies in other solid organ transplants in children, that systemic inequities exist in this field. While data relating specifically to pediatric lung transplantation are relatively sparse, professionals should be aware of the risk that healthcare systems may result in disparities in access and outcomes following lung transplantation in children.

Self-reported engagement in everyday activities following bilateral lung transplantation in paediatric cystic fibrosis: a single centre study

IntroductionFollowing lung transplantation, it is unknown how children/adolescents self-assess their performance in everyday activities, importance of these activities, and whether resumption of everyday activities influences self-reported quality of life. The...

ERS 2023 Abstract Highlights

The following highlights spotlight selected abstracts presented at the European Respiratory Society (ERS) International Congress 2023. They cover key topics, including persistent airflow limitation in paediatric severe asthma, pulmonary rehabilitation, health-related quality of life, chronic cough and obstructive sleep apnoea, paediatric lung transplantation, dead space ventilation in acute respiratory distress syndrome, and virtual wards for remote patient monitoring.

From 6-wk Lungs to 6 y: Increasing the Donor Pool for Pediatric Lung Transplantation.

Lung transplantation in the pediatric population is a challenge. With the donor pool being so small and lungs from young donors rare and precious, every organ available needs to be utilized to its best potential. Here, we describe the case of a 6-wk-old donor of double lungs to a 5-mo-old baby girl diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins. The recipient is doing very well, 6 y after the transplant, now following normal growth. The challenges facing pediatric cardiothoracic transplantation in terms of organ supply and demand are enormous. In this article, we discuss some of the issues around the shortage of organs and alternatives to increase the organ donor pool.

Successful management of temporary veno-venous extracorporeal membrane oxygenation for a pediatric lung transplant recipient with bronchiolitis obliterans syndrome awaiting lung re-transplantation: a case report

BackgroundThe use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging.Case presentationA 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted.ConclusionsVV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.

Reality of DCD donor use in pediatric thoracic transplantation in the United States

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.

Poor functional status at the time of waitlist for pediatric lung transplant is associated with worse pretransplant outcomes

Whether functional status is associated with survival to pediatric lung transplant is unknown. We hypothesized that completely dependent functional status at waitlist registration, defined using Lansky Play Performance Scale (LPPS), would be associated with worse outcomes. Retrospective cohort study of pediatric lung transplant registrants utilizing United Network for Organ Sharing's Standard Transplant Analysis and Research files (2005-2020). Primary exposure was completely dependent functional status, defined as LPPS score of 10-40. Primary outcome was waitlist removal for death/deterioration with cause-specific hazard ratio (CSHR) regression. Subdistribution hazard regression (SHR, Fine and Gray) was used for the secondary outcome of waitlist removal due to transplant/improvement with a competing risk of death/deterioration. Confounders included: sex, age, race, diagnosis, ventilator dependence, extracorporeal membrane oxygenation, year, and listing center volume. A total of 964 patients were included (63.5% ≥ 12 years, 50.2% cystic fibrosis [CF]). Median waitlist days were 95; 20.1% were removed for death/deterioration and 68.2% for transplant/improvement. Completely dependent functional status was associated with removal due to death/deterioration (adjusted CSHR 5.30 [95% CI 2.86-9.80]). This association was modified by age (interaction p=0.0102), with a larger effect for age ≥12 years, and particularly strong for CF. In the Fine and Gray model, completely dependent functional status did not affect the risk of removal due to transplant/improvement with a competing risk of death/deterioration (adjusted SHR 1.08 [95% CI 0.77-1.49]). Pediatric lung transplant registrants with the worst functional status had worse pretransplant outcomes, especially for adolescents and CF patients. Functional status at waitlist registration may be a modifiable risk factor to improve survival to lung transplant.

Pediatric Lung Transplant Outcomes Based on Immunosuppressive Regimen at Discharge: Retrospective Cohort Study Using Real-World Evidence From the US Scientific Registry of Transplant Recipients

This retrospective analysis of the US Scientific Registry of Transplant Recipients was undertaken to obtain real-world evidence concerning the efficacy and safety of tacrolimus-based immunosuppression in pediatric lung transplant recipients to support a supplemental New Drug Application. Overall, 725 pediatric recipients of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for up to 3 years post-transplant based on an immunosuppressive regimen at hospital discharge: immediate-release tacrolimus (TAC)+mycophenolate mofetil (MMF), TAC+azathioprine (AZA), cyclosporine (CsA)+MMF, or CsA+AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 year post-transplant, calculated by Kaplan-Meier analysis. The use of TAC+MMF increased over time. During 2010 to 2017, 91.7% of pediatric lung transplant recipients were receiving TAC+MMF at the time of discharge. The proportion of recipients continuing their discharge regimen at 1 year post-transplant was 83.7% with TAC+MMF and 40.4% to 59.7% with the other regimens. Cumulative incidence of the composite endpoint of graft failure or death at 1 year post-transplant was 7.7% with TAC+MMF, 13.9% with TAC+AZA, 8.9% with CsA+MMF, and 9.1% with CsA+AZA. There was no significant difference in the risk of graft failure or death at 1 year post-transplant between groups from 1999 to 2005 (the only era when adequate numbers on each regimen allowed statistical comparison). No increase in hospitalization for infection or malignancy was seen with TAC+MMF. The real-world evidence from the US database of transplant recipients supported the Food and Drug Administration's approval of tacrolimus-based maintenance immunosuppression in pediatric lung transplant recipients.

Extracorporeal membrane oxygenation bridge to pediatric lung transplantation: Modern era analysis.

Survival outcomes of children on extracorporeal membrane oxygenation (ECMO) at time of lung transplant (LTx) remain unclear. Pediatric first-time LTx recipients transplanted between January 2000 and December 2020 were identified in the United Network for Organ Sharing Registry to compare post-transplant survival according to ECMO support at time of transplant. For a comprehensive analysis of the data, univariate analysis, multivariable Cox regression, and propensity score matching were performed. During the study period, 954 children under 18 years of age underwent LTx with 40 patients on ECMO. We did not identify a post-LTx survival difference between patients receiving ECMO when compared to those that did not. A multivariable Cox regression model (Hazard ratio = 0.83; 95% confidence interval: 0.47, 1.45; p = .51) did not demonstrate an increased risk for death post-LTx. Lastly, a propensity score matching analysis, retaining 33 ECMO and 33 non-ECMO patients, further confirmed no post-LTx survival difference comparing ECMO to no ECMO cohorts (Hazard ratio = 0.98; 95% confidence interval: 0.48, 2.00; p = .96). In this contemporary cohort of children, the use of ECMO at the time of LTx did not negatively impact post-transplant survival.