For mastering bronchoscope handling, positioning, and directing of the bronchoscope in response to the intraluminal view provided by the bronchoscope camera, sufficient training is necessary, ...especially in infants and toddlers who have smaller airways, faster respiratory rates, and higher airway collapsibility. With the use of three‐dimensional printing, we aimed to develop a set of anatomically accurate and low‐cost airway models for teaching and training of bronchoscopy technique and foreign body removal: a translucent airway box model, a static airway model, and a dynamic airway model consisting of a flexible tree model connected to a pump that allows simulation of airway collapsibility during breathing. Computed tomography (CT) patient data of three different ages (1, 5, and 18 years of age) was imported into Materialise Mimics, segmented, and printed using VisoClear and soft Tango+ material. The models were evaluated by three pediatric pulmonology attendings for anatomical accuracy and usefulness for teaching and training. The translucent airway box model was preferred for the initial presentation of bronchoscope handling and learning anatomy in three dimensions. The static and flexible tree models were used to train bronchoscope handling and foreign body removal. The dynamic model provided the most realistic representation of a pediatric airway throughout the respiratory cycle with increased patency during inspiration and relative collapse during exhalation. Objective verification of anatomical accuracy and physiology of breathing motion was obtained by comparing CT scans of the model with original images and by application of 4D dynamic CT airway imaging protocols, respectively.
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.
Stent angioplasty of patent ductus arteriosus has been shown to be a viable alternative to operative shunt placement in cyanotic neonates. With broader implementation of this strategy, novel ...complications are bound to arise. We present a series of cases evaluated for ductal stent angioplasty in which a dilated and torturous ductus arteriosus compressed the left mainstem bronchus. After reviewing our recent experience with ductal stenting and isolated Blalock‐Taussig shunts, our best estimate of the incidence of bronchial compression by the dilated ductus is 4.6% (3/64, 95% confidence interval 1.0–12.9%). Awareness of the airway and other nonvascular contents of the thorax is an important consideration prior to ductal stenting.
The members of the cytoplasmic 70-kDa heat shock protein family are involved in appropriate folding and trafficking of newly synthesized proteins in the cell. Hsc70, which is expressed ...constitutively, and Hsp70, the expression of which is stress- and heat shock-induced, are often considered to have similar cellular functions in this regard, but there are suggestions that the intracellular functions of these homologous but not identical proteins may differ. We tested the hypothesis that Hsc70 and Hsp70 would have differential effects on the expression of the epithelial sodium channel (ENaC). In Xenopus oocytes, overexpression of human Hsc70 decreased the functional (defined as amiloride-sensitive whole-oocyte current) and surface expression of murine ENaC (mENaC) in a concentration-dependent fashion. In contrast, coinjection of a moderate amount of Hsp70 cRNA (10 ng) increased the functional and surface expression of mENaC, whereas a higher amount of coinjected Hsp70 cRNA (30 ng) decreased mENaC functional and surface expression. The increase in mENaC functional expression with coinjection of 10 ng of Hsp70 cRNA was antagonized by the additional coinjection of Hsc70 cRNA in a concentration-dependent fashion. These data are consistent with Hsc70 and Hsp70 having differential and antagonistic effects with regard to the intracellular trafficking of mENaC in oocytes, which may have an impact on our understanding and potential treatment of diseases of aberrant ion channel trafficking.
Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric ...lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow‐up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent‐to‐treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre‐ and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy‐five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre‐enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long‐term remote intervention, and their medication blood levels stabilized. NCT02266888.
This multisite trial evaluates a remote intervention targeting medication adherence in pediatric lung transplant recipients, finding that patients and their families can be successfully engaged over a long follow‐up period and that the intervention stabilizes medication blood levels.
Anelloviruses are DNA viruses ubiquitously present in human blood. Due to their elevated levels in immunosuppressed patients, anellovirus levels have been proposed as a marker of immune status. We ...hypothesized that low anellovirus levels, reflecting relative immunocompetence, would be associated with adverse outcomes in pediatric lung transplantation. We assayed blood samples from 57 patients in a multicenter study for alpha‐ and betatorquevirus, two anellovirus genera. The primary short‐term outcome of interest was acute rejection, and longer‐term outcomes were analyzed individually and as “composite” (death, chronic rejection, or retransplant within 2 years). Patients with low alphatorquevirus levels at 2 weeks post‐transplantation were more likely to develop acute rejection within 3 months after transplant (P = .013). Low betatorquevirus levels at 6 weeks and 6 months after transplant were associated with death (P = .047) and the composite outcome (P = .017), respectively. There was an association between low anellovirus levels and adverse outcomes in pediatric lung transplantation. Alphatorquevirus levels were associated with short‐term outcomes (ie, acute rejection), while betatorquevirus levels were associated with longer‐term outcomes (ie, death, or composite outcome within 2 years). These observations suggest that anelloviruses may serve as useful biomarkers of immune status and predictors of adverse outcomes.
Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates.
To examine the relationship between lung ...transplant candidate height and waiting list outcomes.
We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year.
The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval CI, 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation.
Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.
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.
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