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Background: Since lung transplantation became a viable option for cystic fibrosis (CF) lung disease, adult transplant recipients with CF have superior survival than all the other major diagnostic indications. However, among adults, recipients with CF have a younger age at transplant than other transplant recipients. Over time, the frequency and proportion of lung transplants for CF has increased for adults compared with children. Using a large international transplant registry, we investigated time trends in numbers of transplants, age at transplant, and post-transplant survival and cause of death for recipients with CF., Methods: We conducted a retrospective cohort study of primary lung-alone deceased-donor transplants with a primary diagnostic indication of CF reported to the International Society for Heart and Lung Transplantation Thoracic Transplant Registry from January 2005 through December 2014. We assessed outcomes through December 31, 2015. The study defined the pediatric group as age <18 years at transplant and the adult as ≥18 years at transplant. We assessed time trends (Era I 2005-2009, Era II 2010-2014) in age and compared post-transplant outcomes of age sub-groups with Kruskal-Wallis or chi-square tests. Kaplan-Meier survival analysis estimated the incidence of survival, censoring for loss to follow-up, end of study, and retransplant. In addition, we compared outcomes in age groups and transplant eras with the log-rank test., Results: Of the 5,613 transplanted recipients with CF, the pediatric group comprised 10.9% and the adult group comprised 89.1%. Of the adults, 73.3% were aged 18 to 39 years and 15.9% were ≥40 years old. During Era I, 2,508 of transplant recipients had CF, whereas 3,105 recipients had CF in Era II (p < 0.001). Comparing Era I with Era II, recipient mean age increased from 28.4 years to 29.5 years (p < 0.001) and the proportion of pediatric CF recipients dropped from 12.4% to 9.6% (p < 0.001), whereas the proportion with age ≥40 years increased from 14.2% to 17.2% (p < 0.001). Mean donor age was significantly lower in children than in recipients aged 18 to 39 years and ≥40 years (17.0 vs 37.0 vs 41.0 years, p < 0.001). Pediatric CF transplant recipients had lower survival in the first 3 years post-transplant than adults (p < 0.0001). Chronic graft failure caused most pediatric deaths, whereas infection was the leading cause of death in adult recipients., Conclusion: As survival of patients with CF has improved in recent decades, the mean age of lung transplant recipients with CF has increased. Currently, an increasing number of adults undergoes lung transplant for this indication. Adult CF transplant recipients continue to have better survival than pediatric recipients, and among adults, older adults have had better survival than younger adults., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population., (© 2017 Wiley Periodicals, Inc.)

Background: Prospective studies to determine associated risk factors and related outcomes for pulmonary fungal infection (PFI) after pediatric lung transplant (PLT) are lacking., Methods: NIH-sponsored Clinical Trials in Organ Transplantation in Children enrolled PLT candidates, collecting data prospectively for 2 years post-transplant. Demographics, signs/symptoms, radiology, pathology and microbiology were collected. Analyses evaluated for PFI-related risks and outcomes., Results: In 59 PLT, pre-transplant fungal colonization occurred in 6 donors and 15 recipients. Cystic fibrosis (CF) was associated with pre-transplant colonization (P < .01). Twenty-five (42%) PLT had 26 post-transplant colonizations (median = 67 days, range = 0-750 days) with Candida (13), Aspergillus (4), mold (6) or yeast (3). Post-PLT colonization was not associated with CF, age, or pre-PLT colonization. Thirteen PFIs occurred in 10 (17%) patients, 3 proven (Candida species) and 10 probable (Candida [3], Aspergillus [3], Penicillium [3], and mold [1]). Pulmonary fungal infection was preceded by post-PLT colonization with the same organism in 4 of 13 PFI, but post-PLT colonization did not predict subsequent PFI (P = .87). Older age at transplant was a risk for PFI (P < .01). No mortality was attributed to PFI. Prophylaxis use was not associated with decreased post-PLT colonization (P = .60) or PFI (P = .48)., Conclusion: In PLT, PFI and fungal colonization are common but without associated mortality. Post-PLT colonization did not predict PFI. Optimal prevention strategies require additional study., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival., (© 2016 Steunstichting ESOT.)

Bilateral lung transplantation remains a treatment for end-stage cystic fibrosis (CF) lung disease when there is no further medical or surgical treatment available. The aim of lung transplantation is to improve patient life expectancy. The consensus view that lung transplantation extends life in children has been challenged. However, challengers have faced alternative explanations of their finding and it is largely accepted that lung transplantation in the adolescent patient population is an important treatment modality. The goal of this article is to address these concerns and assist with developing creative approaches to this known challenging subset of patients. The main focus of this article will be to discuss the looming question: what existing evidence or best practice insights could improve bilateral lung transplantation outcomes for adolescent patients with end-stage CF?

In their provocative paper, "Lung transplantation and survival in children with cystic fibrosis," Liou and colleagues state that "Prolongation of life by means of lung transplantation should not be expected in children with cystic fibrosis. A prospective, randomized trial is needed to clarify whether and when patients derive a survival and quality of life benefit from lung transplantation." Unfortunately, that conclusion is not supportable. Liou's dataset introduced bias against transplantation by using covariates obtained well before the time of transplant (when predicted survival was good) and having a cohort with lower than expected post-transplant survival than reported elsewhere. The calculated hazard ratios are based on factors that may have changed between listing and transplant, and do not reflect true benefit on a patient by patient basis. The findings of the study are contrary to other studies using similar methods. Finally, recent changes in US lung transplant allocation policy may have made the study findings moot. In contrast to Liou's suggestion to perform an ethically and logistically challenging randomized trial to verify the benefit of lung transplantation, a research agenda is recommended for pediatric lung transplantation for cystic fibrosis that focuses on developing strategies to continually reassess and maximize quality of life and survival benefit.

Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction (CLAD), in adults. However, PGD associations with long-term outcomes following pediatric lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48- or 72-hours would be associated with shorter CLAD-free survival following pediatric lung transplantation. This was a single center retrospective cohort study of patients ≤ 21 years of age who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of follow-up. PGD and CLAD were defined by published criteria. We evaluated the association of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses. Fifty-one patients were included (median age 12.7 years; 51% female). The most common transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%). Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis, PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI 1.01-4.37, p =0.047). This association remained when adjusting individually for multiple potential confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20). PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with shorter CLAD-free survival. Sex may be a modifier of this association. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]