Lung Transplant Program Research Articles

Beyond Borders: International Immunosuppression Practices in Pediatric Lung Transplantation

ABSTRACTIntroductionCurrent recommendations for lung transplantation immunosuppression do not explicitly target children, and many pharmacotherapies used in pediatrics are extrapolated from adults.MethodsData were collected from an anonymous survey distributed to International Pediatric Lung Transplant Collaborative (IPLTC) members from November 2023 to February 2024. Eligible participants included pediatric lung transplant physicians, pharmacists, or others with expertise in their lung transplant center's protocols. Participant and program demographics were surveyed, including location and transplant volume. Seventeen multiple‐choice questions, text responses, and Likert scale statements covered the following: induction immunosuppression, maintenance immunosuppression, drug monitoring, dose optimization, and expert guidance available in current literature.ResultsAmong the 23 pediatric lung transplant healthcare professionals who responded, 13 respondents (57%) preferred using basiliximab as their standard induction immunosuppression. 3 (13%) prefer rabbit anti‐thymocyte globulin (rATG), while 7 (30%) consider either rATG or basiliximab for induction. Of 22 responses with 100% completion, 21 of 22 (95.2%) respondents reported a combination of tacrolimus, mycophenolate mofetil (MMF), and corticosteroids (CCS) as their preferred maintenance immunosuppression regimen, reflecting the suggested preferred regimen for pediatric lung transplantation. Feedback on the perception of available evidence‐based or established guidelines revealed the majority (90.0%) of respondents found them to be insufficient for pediatrics.ConclusionThis international survey highlights the variability in immunosuppression practices across pediatric lung transplant programs around the world. The findings underscore a gap in unified, evidence‐based practice guidelines. With strong consensus among respondents on the lack of established guidelines, there is a clear directive for future research to establish standardized practices in pediatric lung transplantation.

Ambient Air Pollution Exposure and Outcomes in Patients Receiving Lung Transplant

Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood. To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants. This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023. Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates. The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality. Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code's annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable. In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

The impact of exvivo lung perfusion location on lung transplant outcomes.

Ex vivo lung perfusion (EVLP) conducted outside of the transplant center has increased in recent years to mitigate its limitation by resources and expertise. We sought to evaluate EVLP performed at transplant centers and externally. Lung transplant recipients were identified from the United Network for Organ Sharing Database. Recipients were then stratified into two groups based where they were perfused: Transplant Program (TP) or External Perfusion Centers (EPC). The groups were assessed with comparative statistics and long-term survival was assessed by Kaplan-Meier method. The groups were then 1:1 propensity and this process was repeated. EPC use was generally restricted to the Southern United States. Following matching, there were no significant differences in post-operative outcomes to include post-operative stroke, dialysis, airway dehiscence, ECMO use, ventilator use or incidence of primary graft dysfunction Grade 3. Adjusted 3-year survival was 68.9% (95% Confidence Interval [CI]: 60.9%-77.9%) for the TP group and 67.6% (95% CI: 61.0%-74.9%) for the EPC group (p = 0.69). In allografts with extended ischemia (14+ h), those in the TP group had significantly longer length of stay, prolonged ventilation and treated rejection in the 1st year, though no significant difference in mid-term survival (p = 0.66). EVLP performed at an EPC can be carried out with results and survival similar to allografts undergoing EVLP at a TP. EPCs will extend the valuable resource of EVLP to lung transplant programs without the resources to perform EVLP.

Experience of a novel lung transplant program in Mexico.

Lung transplantation is the gold standard therapy for patients in the end stages of pulmonary disease. However, in numerous countries, candidates for lung transplants often die on the waiting list due to a shortage of donors and limited access to transplant centers. This article delves into the experience of our hospital, Christus Muguerza in Monterrey, Mexico, as the sole active lung transplant program in the country, having conducted 35 transplants from August 2017 to March 2023. We discuss the actual situation of lung transplantation in Mexico and the challenges we have faced over time, such as late patient referrals for evaluation and eventual transplantation. In addition, we outline the challenges we anticipate as more transplant programs emerge in the country.

Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1year following lung transplantation from HCV-viremic versus uninfected donors. We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. We demonstrate the feasibility and success of using HCV NAT+donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.

Patient perspectives on elexacaftor/tezacaftor/ivacaftor after lung transplant

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/tezacaftor/ivacaftor (ETI), significantly improve outcomes and quality of life for people with cystic fibrosis (CF). However, little is known about how lung transplant recipients (LTRs) perceive the use of ETI. We conducted a survey to assess perspectives on ETI among LTRs with CF at our lung transplant program. Of 81 CF LTRs, 46 participants (58 %) responded. The majority of respondents (88 %) were aware of ETI. Over 80 % considered treating non-lung symptoms of CF to be very important. Concerns regarding ETI included potential drug interactions with transplant medications (77 %), side effects (53 %), cost of medication (49 %), and lack of clinical trial data for LTRs (43 %). Half reported they would only consider taking ETI if their CF or transplant doctor recommended it. The findings suggest that CF LTRs seek informational support and shared decision-making about ETI from their clinicians.

Oesophageal stasis is a risk factor for chronic lung allograft dysfunction and allograft failure in lung transplant recipients.

Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.

Design and evaluation of a Mobile-Based decision support system to enhance lung transplant candidate assessment and management: knowledge translation integrated with clinical workflow

BackgroundAccurate and timely decision-making in lung transplantation (LTx) programs is critical. The main objective of this study was to develop a mobile-based evidence-based clinical decision support system (CDSS) to enhance the management of lung transplant candidates.MethodAn iterative participatory software development process was employed to develop the ImamLTx CDSS. This study was accomplished in three phases. First, required data and standard clinical workflow were identified according to the literature review and expert consensus. Second, a rule-based knowledge-based CDSS application was developed. In the third phase, this CDSS was evaluated. The evaluation was done using the standard Post-Study System Usability Questionnaire (PSSUQ 18.3) and ten usability heuristics factors for user interface design.ResultsAccording to expert consensus, fifty-five data items were identified as essential data sets using the Content Validity Ratio (CVR) formula. By integrating information flow in clinical practices with clinical protocols, more than 450 rules and 500 knowledge statements were extracted. This CDSS provides clinical decision support on an Android platform regarding inclusion and exclusion referral criteria, optimum transplant time based on the type of lung disease, findings of initial assessment, and the overall evaluation of lung transplant candidates. Evaluation results showed high usability ratings due to the fact provided accuracy and sensitivity of this lung transplant CDSS with the information quality domain receiving the highest score (6.305 from 7).ConclusionThrough a stepwise approach, the ImamLTx CDSS was developed to provide LTx programs with timely patient data access via a mobile platform. Our results suggest integration with existing workflow to support clinical decision-making and provide patient-specific recommendations.

Association of Heart Transplant Volume with Presence of Lung Transplant Programs and Heart Transplant's SRTR One-year Survival Rating.

Several factors affect heart transplant (HTx) and lung transplant (LTx) program outcomes. Variabilities in institutional and community characteristics have been shown to influence survival. At present, half of HTx centers in the United States do not possess a concomitant LTx program. This study sought to better understand the characteristics of HTx with and without LTx programs. Nationwide transplant data were collected from the Scientific Registry of Transplant Recipients (SRTR) in August 2020. SRTR star rating ranges from tier 1 (lowest) to tier 5 (highest). HTx volumes and SRTR star ratings for survival were compared between the centers with heart-only (H0) programs and the centers with heart-lung (HL) programs. SRTR star ratings were available for 117 transplant centers with one or more HTx reported. The median number of HTx performed over 1 year was 16 (interquartile range [IQR]: 2-29). The number of HL centers (n = 67, 57.3%) were comparable to H0 centers (n = 50, 42.7%; p = 0.14). The HTx volume at the HL centers (28 [IQR: 17-41]) exceeded the HTx volume at the H0 centers (13 [IQR: 9-23]; p < 0.01), but were comparable to the LTx volume at the HL centers (31 [IQR: 16-46]; p = 0.25). The median HTx one-year survival rating was 3 (IQR: 2-4) at both the H0 and HL centers (p = 0.85). The HTx and LTx volumes were positively associated with the respective 1-year survivals (p < 0.01). While the presence of an LTx program is not directly associated with HTx survival, it has a positive association with the HTx volume. The HTx and LTx volumes are positively associated with the 1-year survival.

P354 West Midlands Adult Cystic Fibrosis Centre experience of the effects of Kaftrio® on patients within the lung transplant programme

The effects of Kaftrio are known to have a positive impact on the health of people with CF. Clinical trials for Kaftrio have shown 10% increase in lung function. Lung transplant is an option for pwCF with advanced lung disease. We reviewed patients’ response to Kaftrio on the lung transplant programme.

Twenty-Five Years of Lung Transplantation in Medellín: Overcoming the Challenges of an Emerging Country

The first successful lung transplant in Colombia was performed on October 28, 1997 in Medellín by Alberto Villegas Hernández at the "Clínica Cardiovascular Santa María" today called the Cardio VID Clinic. Here we present both survival outcomes and characteristics of the oldest and most experienced lung transplant program in Colombia. We conducted a retrospective study of all patients taken to lung transplantation at the Cardio VID Clinic in Medellín, Colombia from October 1997 to October 2022. Patient information from our institutional database and transplant archives were retrieved and reviewed. From October 1997 to October 2022, a total of 153 patients underwent orthotopic lung transplantation at our institution in Medellín, Colombia. Mean recipient age was 48 ± 13 years, the youngest patient was 15 years old and the oldest patient was 73 years old at the time of transplant. Seventy-four (48.4%) patients were men and seventy-nine (51.6%) were women. Uncensored lung transplant survival in Medellin at 1 month, 1 year, 5 years, and 10 years were 68%, 50%, 31%, and 12%, respectively. Although health care coverage in Colombia reaches nearly 100%, socioeconomic hurdles during post-transplant care, nonreturning patients, infections, and traumatic donor deaths lead to high mortality rates. Due to these factors, establishing successful and sustainable lung transplant programs in these settings is challenging.

Prevalence of Violence against Providers in Heart and Lung Transplant Programs

Workplace violence in healthcare institutions is becoming more frequent. The objective of this study was to better understand the nature of threat and physical acts of violence from heart and lung transplant patients and families toward healthcare providers and suggest programmatic mitigation strategies. We administered a brief survey to attendees at the 2022 International Society of Heart and Lung Transplantation Conference in Boston, Massachusetts. A total of 108 participants responded. Threats of physical violence were reported by forty-five participants (42%), were more frequently reported by nurses and advanced practice providers than physicians (67% and 75% vs. 34%; p < 0.001) and were more prevalent in the United States than abroad (49% vs. 21%; p = 0.026). Acts of physical violence were reported by one out of every eight providers. Violence against providers in transplant programs warrants closer review by health systems in order to ensure the safety of team members.

Lung Transplantation in India: a Brief Review, Landmarks, Indian Scenario, and our Experience.

Lung transplantation is gaining widespread acceptance as the preferred therapeutic option for selected cases of end-stage lung disease in India. The indications of lung transplantation are increasing, with better post-operative survival, including the COVID affected lung, if we choose our patients well. The national acceptance of expanded criteria in lung donation, streamlining of the process of lung transplantation by governmental, and non-governmental organizations and significant increase in the number of organ donations in India have strengthened the lung transplantation program within the country. Through this article, we describe a brief history, the process, and our experience of lung transplantation since we started our program in 2017 until date.

Triaging donor lungs based on a microaspiration signature that predicts adverse recipient outcome

Aspiration is a relative contraindication to accepting donor lungs for transplant and is currently assessed by visual inspection of the airways via bronchoscopy. However, this method is limited as it does not assess for microaspiration. Bile acids measured in large airway bronchial wash (LABW) samples have been shown to be a marker of aspiration in lung transplant recipients. Herein, we investigate the utility of measuring total bile acids (TBA) in donor LABW to predict performance of donor lungs and recipient outcomes. TBA was measured in 605 consecutive lung donors at the Toronto Lung Transplant Program. TBA levels were compared in donor lungs deemed unsuitable for transplant, requiring further assessment on ex vivo lung perfusion (EVLP), and those suitable for direct transplantation using Mann-Whitney-U tests. Relationships between LABW TBA concentrations and recipient outcomes were evaluated using multivariable Cox-PH models and log-rank analysis. Donor TBA was highest in lungs deemed unsuitable for transplant and correlated with clinical assessment of aspiration. LABW TBA concentration correlated with calcium, decreased pH, and increased pro-inflammatory mediators in EVLP perfusate. TBA cut-off of 1245 nM was able to differentiate donor lungs directly declined from those suitable for direct transplantation with a 91% specificity (AUROC: 73%). High donor TBA status was associated with the increased rate of primary graft dysfunction, longer time to extubation, and shorter time to chronic lung allograft dysfunction. In a large retrospective cohort, we observed that donor LABW TBA was associated with suitability of donor lungs for transplant, performance of the organ on EVLP, and adverse recipient outcomes.

The Use of Intraoperative Extracorporeal Membrane Oxygenation in Lung Transplantation: Initial Institutional Experience.

Lung transplantation is the final treatment option for end-stage lung disease, and extracorporeal membrane oxygenation (ECMO) is increasingly being used during lung transplantation. The present study aimed to review our initial experience with patients who underwent lung transplantation with or without ECMO since the implementation of the lung transplantation program at our center. Data were prospectively collected on all patients between December 2016 and December 2018. Patients undergoing ECMO as a bridge to lung transplantation were excluded. A total of 48 lung transplants were performed, and ECMO was used in 29 (60.4%) cases. Twenty (83%) patients were female. The median age was 48.5 (range, 14-64) years. The most common indications were idiopathic interstitial pneumonia in 9 (31%) patients, chronic obstructive pulmonary disease in 7 (24.1%) patients, and bronchiectasis in 6 (20.7%) patients. Sequential bilateral lung transplantation was performed in all patients. The 30-day mortality was 20.6% (6/29) for patients with ECMO, however, it was 10.5 (2/19) for patients without ECMO (P=0.433). The median length of stay in the intensive care unit (ICU) was 5 (range, 2-25) days. The ECMO weaning rate was 82.8% (24/29). One-year survival was 62.1% with ECMO versus 78.9% without ECMO, and the 3-year survival was 54.1% versus 65.8%, respectively (P=0.317). ECMO is indicated for more severe patients who underwent lung transplantation. The use of ECMO provides adjuvant support during surgery and the mortality rate is acceptable. Survival is also as similar as non-ECMO patients. ECMO is appropriate for critically ill patients.

New Aspects of Lung Transplantation: A Narrative Overview Covering Important Aspects of Perioperative Management.

The management of lung transplant patients has continued to evolve in recent years. The year 2021 was marked by the publication of the International Consensus Recommendations for Anesthetic and Intensive Care Management of Lung Transplantation. There have been major changes in lung transplant programs over the last few years. This review will summarize the knowledge in anesthesia management of lung transplantation with the most recent data. It will highlight the following aspects which concern anesthesiologists more specifically: (1) impact of COVID-19, (2) future of transplantation for cystic fibrosis patients, (3) hemostasis management, (4) extracorporeal membrane oxygenation management, (5) early prediction of primary graft dysfunction, and (6) pain management.

Fungal infection and colonization in lung transplant recipients with chronic lung allograft dysfunction.

The incidence and impact of de novo fungal airway colonization and infection in lung transplant recipients (LTRs) with known chronic lung allograft dysfunction (CLAD) has not been established. We aimed to determine the 1-year cumulative incidence and risk factors of de novo fungal colonization or infection in LTRs with CLAD and assess the impact of colonization or infection on post-CLAD survival. Prospectively collected Toronto Lung Transplant Program database and chart review were used for double-LTRs who were diagnosed with CLAD from January 1, 2016 to January 1, 2020 and who were free of airway fungi within 1 year prior to CLAD onset. International Society for Heart and Lung Transplantation definitions were used to define clinical syndromes. Cox-Proportional Hazards Models were used for risk-factor analysis. Survival analysis could not be completed secondary to low number of fungal events; therefore, descriptive statistics were employed for survival outcomes. We found 186 LTRs diagnosed with CLAD meeting our inclusion criteria. The 1-year cumulative incidence for any fungal event was 11.8% (7.0% for infection and 4.8% for colonization). Aspergillus fumigatus was a causative pathogen in eight of 13 (61.5%) patients with infection and six of nine (66.7%) patients with colonization. No patients with fungal colonization post-CLAD developed fungal infection. Peri-CLAD diagnosis (3 months prior or 1 month after) methylprednisolone bolus (hazards ratio: 8.84, p = .001) increased the risk of fungal events. Most patients diagnosed with fungal infections (53.8%) died within 1-year of CLAD onset. De novo IFIs and fungal colonization following CLAD onset were not common. Fungal colonization did not lead to fungal infection. Methylprednisolone bolus was a significant risk factors for post-CLAD fungal events.

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d=18), a frailty index (FI, d=66) and a lifestyle/social vulnerability index (LSVI, d=10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Improved Outcomes for Infants and Young Children Undergoing Lung Transplantation at Three Years of Age and Younger.

Rationale: Since its inception, older children and adolescents have predominated in pediatric lung transplantation. Most pediatric lung transplant programs around the world have transplanted few infants and young children. Early mortality after lung transplantation and inadequate donor organs have been perceived as limitations for success in lung transplantation at this age. Objectives: Our aim was to describe our experience in a large pediatric lung transplant program with respect to lung transplantation in infants and young children, focusing on diagnosis, waitlist, and mortality. Methods: We performed a retrospective review of infants and young children under 3 years of age at the time of transplant in our program from 2002 through 2020. Results: The patient cohort represented a severely morbid recipient group, with the majority hospitalized in the intensive care unit on mechanical ventilation just before transplantation. There was a marked heterogeneity of diagnoses distinct from diagnoses in an older cohort. Waitlist time was shorter than in older age cohorts. There was a decrease in early mortality, lowerincidence of allograft rejection, and satisfactory long-term survival in this age group compared with the older cohort and published experience. Severe viral infection was an important cause of early mortality after transplant. Nonetheless, survival is comparable to older patients, with better enduring survival in those who survive the early transplant period in more recent years. Conclusions: Carefully selected infants and young children with end-stage lung and pulmonary vascular disease are appropriate candidates for lung transplantation and are likely underserved by current clinical practice.