C. Towe

Changing demographics and outcomes of lung transplantation recipients with cystic fibrosis

BACKGROUND Cystic fibrosis (CF) is one of the most common diagnoses in adult and pediatric patients undergoing lung transplantation (LTx). A changing pattern of indications for LTx among patients with CF has been noted. This study analyzes the prevalence and characteristics of patients with CF who underwent LTx in the current era. METHODS A retrospective analysis was performed using data from the United Network of Organ Sharing database of all LTx performed from 1999 to 2013 (N = 20,345). Sub-analyses focused on children (<18 years old). Patients with CF who underwent LTx were assigned to early (1999-2003), mid (2004-2008), and current (2009-2013) eras based on the date of the procedure as well as before and after implementation of the new lung allocation score system in 2005. RESULTS CF was the indication for LTx in 14% (2,877) of who patients underwent LTx, a decrease from >17% in the early era to <13% in the current era (p < 0.001). In the pediatric cohort, CF was the indication for LTx in 383 (53%) patients, a proportion that also decreased across eras (early, 60%; mid, 53%; current, 47%; p = 0.009). The mean age of patients with CF undergoing LTx increased across the eras (early, 28 years ± 10; mid. 28 years ± 10; current, 30 years ± 11; p < 0.001). Pre-transplant ventilator use and incidence of pan-resistant infections also increased (p < 0.001), whereas pre-transplant forced expiratory volume in 1 second and waitlist times decreased (p < 0.001) in patients with CF. Graft survival across the eras remained similar (p > 0.05) at 5.1 years overall. CONCLUSIONS The proportion of LTx performed for CF has significantly decreased over time, a trend especially pronounced in pediatric patients. The change in pre-transplant characteristics across eras indicates a trend to perform LTx in more clinically ill and older patients with CF. The overall post-LTx survival has not changed.

Bronchiolitis obliterans syndrome is not specific for bronchiolitis obliterans in pediatric lung transplant

BACKGROUND Bronchiolitis obliterans (BO) is the leading cause of mortality beyond the first year after pediatric lung transplant, but the performance of an open lung biopsy is often required for diagnosis. Bronchiolitis obliterans syndrome (BOS) is a clinical diagnosis based on spirometric data that is the accepted standard for staging chronic allograft dysfunction. METHODS We determined the sensitivity, specificity, and positive and negative predictive values of BOS for predicting BO in children. A chart review was conducted on 139 open lung biopsies and 43 lung explants performed at our center from 1990 through June 2010 in pediatric recipients of lung transplants. Results were excluded from analysis if insufficient data existed to calculate a stable BOS stage before biopsy/explant. RESULTS The criteria for inclusion in the study were met by 67 open lung biopsies and 31 lung explants. The sensitivity, specificity, positive predictive value, and negative predictive value of BOS for predicting BO were 91.0%, 25.8%, 72.6%, and 57.1%. CONCLUSIONS We found that early declines in lung function are sensitive, but not specific, for BO. The low specificity of BOS for identifying BO illustrates the challenge facing clinicians in determining the etiology of pulmonary decline after lung transplant.

CT chest under general anesthesia: pulmonary, anesthetic and radiologic dilemmas

IntroductionToday’s practice of medicine involves ever more complexpatients whose care is coordinated with multidisciplinaryteams. Caring for these patients can challenge all membersofthehealthcareteam.Sedation/anesthesiaininfants/toddlersas well as uncooperative or intellectually or emotionally im-paired children who require imaging studies of the chest areongoingchallenges.High-qualitycomputedtomography(CT)chest imaging studies inchildrenundergeneral anesthesia areextremely important for accurate interpretation and subse-quent medical decision-making. Anesthesia-induced atelecta-sismayobscureormimictruepathologycreatingasignificantquality issue. Obtaining a high-quality, motion-free chest im-aging study in infants and children under general anesthesiaremainsadifficulttaskinmanyinstitutions.Meticulousatten-tion to anesthesia and imaging techniques and specializedknowledge are required to properly perform and interpretchest imaging studies.In this commentary, we discuss the continuous struggleto obtain high-quality CT chest imaging under general anes-thesia. We will also discuss the major concerns of theanesthesiologist, radiologist and pulmonologist and why co-operation and coordination among these providers are criticalfor an optimal quality study.Pulmonary concernsSimply put, CT imaging of the chest is needed when moreroutine imaging modalities, such as the standard chest radio-graph, are insufficient for either the diagnosis or managementof children with respiratory disease. Given the inherent risks,thedecisiontopursuechestCTsinchildrenisrarelyunder-taken lightly, especially when sedation/anesthesia will be re-quired for an optimal study. Therefore, when inadequate im-ages are obtained to answer the clinical question, parents andclinicians are equally frustrated.Chest CT is superior to conventional chest radiographsbecause of its ability to provide three-dimensional anatomicalorientation, which allows for no overlap of anatomy andexcellent resolution of differences in tissue densities. Forinfants,itisfrequentlyindicatedintheevaluationofsuspectedinterstitial lung diseases or congenital anomalies [1]. In somecases of interstitial lung diseases, typical presentations ofneuroendocrine cell hyperplasia of infancy for example, aproperlyperformedchestCTisdiagnostic[2],thusalleviatingthe need for more invasive procedures like surgical lungbiopsy. Even when surgical lung biopsy is necessary, pre-biopsy chest CT highlights areas of greatest pathologicalinvolvement increasing the likelihood of diagnosis.In cases of suspected mediastinal or congenital anomalies,the three-dimensional images provided by chest CTallow forboth diagnosis and presurgical planning, if necessary. Vascu-lar anomalies such as vascular rings or vascular slings can besuggested by other imaging modalities such as contrastesophagram, but a chest CT is usually performed to confirmthe diagnosis and delineate the precise anatomy or associated

Infants with Atypical Presentations of Alveolar Capillary Dysplasia with Misalignment of the Pulmonary Veins Who Underwent Bilateral Lung Transplantation

Objective To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. Study design We reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post‐transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Childrens Hospital. We compared their histology with infants with classic ACDMPV and compared their outcomes with infants transplanted for other indications. Results In contrast with neonates with classic ACDPMV who present with severe hypoxemia and refractory pulmonary hypertension within hours of birth, none of the infants with atypical ACDMPV presented with progressive neonatal respiratory failure. Three infants had mild neonatal respiratory distress and received nasal cannula oxygen. Three other infants had no respiratory symptoms at birth and presented with hypoxemia and pulmonary hypertension at 2‐3 months of age. Bilateral lung transplantation was performed at 4‐20 months of age. Unlike in classic ACDMPV, histopathologic findings were not distributed uniformly and were not diffuse. Three subjects had apparent nonmosaic genetic defects involving FOXF1. Two infants had extrapulmonary anomalies (posterior urethral valves, inguinal hernia). Three transplanted children are alive at 5‐16 years of age, similar to outcomes for infants transplanted for other indications. Lung explants from infants with atypical ACDMPV demonstrated diagnostic but nonuniform histopathologic findings. Conclusions The 1‐ and 5‐year survival rates for infants with atypical ACDMPV are similar to infants transplanted for other indications. Given the clinical and histopathologic spectra, ACDMPV should be considered in infants with hypoxemia and pulmonary hypertension, even beyond the newborn period.

Sequence of refusals for donor quality, organ utilization, and survival after lung transplantation

BACKGROUND Lung donor utilization rates remain low, with many organs refused for donor quality. However, some centers have successfully transplanted these organs despite multiple refusals for donor quality (RDQs) by other centers. We hypothesized that the number of refusals due to donor quality does not impact post-transplant outcomes. METHODS Lung transplants (LTxs) from 2006 to 2015, identified using the United Network for Organ Sharing (UNOS) database, were matched against the potential transplant recipient (PTR) data set by donor identification. Transplants were categorized into 2 groups: low RDQ (0 to 3 RDQs) and high RDQ (>3 RDQs). Post-transplant survival and predictors for high RDQ were observed using Kaplan‒Meier and logistic regression analyses, respectively. RESULTS Of 10,126 adult (>18 years) LTxs, 77% had at least 1 RDQ, with a median of 4 RDQs. Post-transplant 1-year survival was similar for both the low and high RDQ groups (p = 0.49). Furthermore, groups of recipients who received donors with an increasing number of RDQs (>3, >6, or >10) also had similar post-transplant 1-year survival (p = 0.77). Treatment for rejection within 1 year and intubation at 72 hours post-transplant were higher in the high RDQ group (p < 0.01). An inverse relationship was identified between the number of RDQs and likelihood of utilization. After 10 RDQs, the likelihood of utilization varied significantly by donor characteristics. CONCLUSIONS Lung transplant survival is not associated with number of refusals due to donor quality. When determining whether an organ is suitable for transplant, the number of refusals due to donor quality should not influence ones decision, especially in this era of limited donor supply.

Ambulatory veno-venous ECMO in adolescents-How far have we walked?

Ever since extracorporeal membrane oxygenation (ECMO) first became clinically widespread, its utilization in pediatric lung transplantation has constantly evolved. Following the first published case series, where only two of nine patients on ECMO at the time of transplant survived to hospital discharge, ECMO was considered a contraindication to lung transplant at most pediatric centers.1 However, with improved outcomes demonstrated by adult lung transplant centers utilizing venovenous (VV) ECMO in particular, along with the development of a double lumen cannula and “awake ECMO” techniques that facilitated patient rehabilitation, ECMO is no longer considered an absolute contraindication to pediatric lung transplantation in highly selected patients.2,3 Unfortunately, because of size limitations in utilizing the double lumen cannulas and the cautious nature of pediatric lung transplantation given the small numbers, the adoption of some of these ECMO practices has been limited and reserved in pediatrics. The multidisciplinary team at Hannover Medical School in Germany has been a leader in adopting these technologies for children, and first published on the concept of pediatric “awake ECMO” in a small case series of three patients in this journal in 2013.3 Since then, the team has learned from their experiences and in select patients reverted to a more traditional dual cannulation approach, but one that is informed by their experiences with single cannulation. In their latest paper, “Back to the Roots? Dual cannulation strategy for ambulatory ECMO in adolescent lung transplant candidates: an alternative?” authors Schmidt et al. describe three adolescent patients with endstage cystic fibrosis successfully bridged to lung transplant awake and ambulating on ECMO using a traditional femoral vein drainage cannula and jugular vein reinfusion cannula.4 To achieve this, they describe making two key modifications to their previous approach: (i) utilizing a more flexible and kink resistant femoral cannula and (ii) using an additional plate to further fix the femoral cannula distal to the entrance site in addition to the standard suture fixation at the entrance site of both the drainage and reinfusion cannulas. They achieved impressive results. The patients were all cannulated without the need for intubation, all were mobilized to the edge of the bed within 8 hours, and one patient was walking within 24 hours. The patients experienced no significant bleeding or other ECMO related complications, and importantly, all three patients survived to lung transplantation. There are significant limitations of the study and questions it raises. Only three cases were described, all the patients were 17 years old with cystic fibrosis, and all were at least 150 cm tall. As one of the main limitations to widespread use of the current double lumen cannulas in pediatrics is patient size, how scalable is the new approach and will it be as successful in younger and smaller patients? The longest time on ECMO in this study was 12 days, and so how durable is this cannulation strategy and will the femoral cannula be able to function adequately during runs of 30 days or longer while stressed by frequent ambulation? Now that patients on ECMO are awake and able to ambulate, what is the optimal rehabilitation and chest physiotherapy approaches to these patients weighing the benefits against the risk of a potentially catastrophic ECMO complication? Despite these limitations, this study is still a significant contribution to the pediatric VV ECMO literature. It will serve as inspiration and guidance for other programs to expand their awake VV ECMO programs to include patients who are not candidates for the double lumen cannulas. While the technical modifications and specific techniques described in the paper are important, undoubtedly the biggest factor allowing patients to be successfully managed with awake ambulatory ECMO is the experience of Hannover’s large multidisciplinary team and the institutional commitment to making this program a success. They have been thoughtful and purposeful in their development of this program, “walking and not running” in its development. For this, not only the authors of this paper, but also the entire team of ICU nurses, physical and respiratory therapists, physicians, surgeons, ECMO specialists, and hospital administrators are to be congratulated.