Objective Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers. Study Design We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains. Results Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge. Conclusion Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD. Key Points

Abstract Introduction Selenoprotein N-related myopathy (SEPN1-RM) is a rare congenital disorder often presenting in infancy or early childhood. Clinical sequelae frequently include progressive muscle weakness, spinal rigidity, respiratory insufficiency, and the need for nocturnal ventilatory support. Here, we describe a teenage athlete who presented with hypercarbia in the sleep lab, required tracheostomy for chronic mechanical ventilation, and was ultimately diagnosed with SEPN1-RM. Report of case(s) We present a 15-year-old male with a remote history of scoliosis repair and obstructive sleep apnea (apnea-hypopnea index [AHI] of 11.1/hour) with subsequent tonsillectomy and adenoidectomy at age 2 years. He had done well until age 15 years when he was referred to Sleep Medicine for morning headaches and daytime sleepiness. At evaluation, he reported working a physically demanding after-school job and playing on the basketball team without any issues. Repeat polysomnography showed an AHI of 88.8/hour, hypoxemia, and hypoventilation with an average transcutaneous carbon dioxide level of 82mmHg, prompting admission to the intensive care unit for further management. After failing non-invasive ventilation due to persistent hypercarbia, he underwent tracheostomy for nocturnal mechanical ventilation. He otherwise tolerated room air during the day. Other notable work-up included evidence of pulmonary hypertension on echocardiogram, oropharyngeal collapse on bronchoscopy, and restriction on pulmonary function tests. Whole exome sequencing eventually revealed SEPN1-RM. The patient was discharged after ventilator training and continues to follow outpatient. Conclusion To date, there is limited understanding on the pathophysiology and clinical course of patients with SEPN1-RM. Our patient’s development of severe obstructive sleep apnea necessitating mechanical ventilation, despite grossly preserved neuromuscular strength and a relatively late onset, does not follow the typical course of other pediatric neuromuscular disorders. His course adds to a small cohort of patients with this disorder and demonstrates its potentially wide clinical spectrum, suggesting further research is needed to better understand this disease process. Support (if any) None.

To characterize a cohort of ventilator-dependent infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) and to describe their cardiorespiratory outcomes. Subjects with BPD on chronic home ventilation were recruited from outpatient clinics. PH was defined by its presence on ≥1 cardiac catheterization or echocardiogram on or after 36 weeks post-menstrual age. Kaplan–Meier analysis was used to compare the timing of key events. Of the 154 subjects, 93 (60.4

OBJECTIVE:To identify factors associated with the timing of ventilator liberation and tracheostomy decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who required chronic outpatient invasive ventilation. STUDY DESIGN:Multicenter retrospective study of 154 infants with sBPD on outpatient ventilators. Factors associated with ventilator liberation and decannulation were identified using Cox regression models and multilevel survival models. RESULTS:Ventilation liberation and decannulation occurred at median ages of 27 and 49 months, respectively. Older age at transition to a portable ventilator and at discharge, higher positive end expiratory pressure, and multiple respiratory readmissions were associated with delayed ventilator liberation. Surgical management of gastroesophageal reflux was associated with later decannulation. CONCLUSIONS:Ventilator liberation timing was impacted by longer initial admissions and higher ventilator pressure support needs, whereas decannulation timing was associated with more aggressive reflux management. Variation in the timing of events was primarily due to individual-level factors, rather than center-level factors.

"The Effects of Air Pollution in Pediatric Respiratory Disease." American Journal of Respiratory and Critical Care Medicine, 207(3), pp. 346–348

"The Greatest LGBTQ+ Health Issue of All Time: Commercial Tobacco." Annals of the American Thoracic Society, 0(ja), pp.

OBJECTIVES To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. METHODS Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. RESULTS There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks’ postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). CONCLUSIONS There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

IntroductionDespite bronchopulmonary dysplasia (BPD) being a common morbidity of preterm birth, there is no validated objective tool to assess outpatient respiratory symptom control for clinical and research purposes. MethodsData were obtained from 1049 preterm infants and children seen in outpatient BPD clinics of 13 US tertiary care centers from 2018 to 2022. A new standardized instrument was modified from an asthma control test questionnaire and administered at the time of clinic visits. External measures of acute care use were also collected. The questionnaire for BPD control was validated in the entire population and selected subgroups using standard methodology for internal reliability, construct validity, and discriminative properties. ResultsBased on the scores from BPD control questionnaire, the majority of caregivers (86.2%) felt their child's symptoms were under control, which did not differ by BPD severity (p = 0.30) or a history of pulmonary hypertension (p = 0.42). Across the entire population and selected subgroups, the BPD control questionnaire was internally reliable, suggestive of construct validity (albeit correlation coefficients were -0.2 to -0.4.), and discriminated control well. Control categories (controlled, partially controlled, and uncontrolled) were also predictive of sick visits, emergency department visits, and hospital readmissions. ConclusionOur study provides a tool for assessing respiratory control in children with BPD for clinical care and research studies. Further work is needed to identify modifiable predictors of disease control and link scores from the BPD control questionnaire to other measures of respiratory health such as lung function testing.

Despite the improving understanding of how lung mechanics and tidal volume requirements evolve during the evolution of bronchopulmonary dysplasia (BPD), clinical management continues to be heterogeneous and inconsistent at many institutions. Recent reports have examined the use of high tidal-volume low respiratory rate strategies in these patients once disease has been well established to help facilitate their eventual extubation and improve their long-term neurodevelopmental outcomes. In this retrospective observational research study, we describe how intentional adjustment of ventilator settings based on patient lung mechanics by an interdisciplinary BPD team improved the care of the at-risk population of infants, reduced the need for tracheostomies, as well as length of stay over a period of over 3 years. The team aimed to establish consistency in the management of these children using a high tidal volume, low-rate approach, and titrating PEEP to address the autoPEEP and bronchomalacia that is frequently observed in this patient population.

Background Bronchopulmonary dysplasia (BPD) remains the most common late morbidity of preterm birth. Clinical care and research have largely focused on the pathogenesis and prevention of BPD. Preterm infants who develop BPD have significant medical needs that persist throughout their hospital course and continue after discharge, including those associated with growth and nutrition. The objective of this study was to review the available literature on nutrition and growth in infants with established BPD and to identify the knowledge and research gaps to provide direction for future studies. Methods We conducted a literature search in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Ovid MEDLINE, CINAHL, and Embase. Titles, abstracts, and full texts were independently reviewed by the authors and selected based on predetermined inclusion/exclusion criteria. Results were summarized qualitatively. Results Excluding duplicates, 2315 articles were identified. Thirty articles were selected for inclusion. We identified the following key components of nutrition support and clinical care: energy expenditure, growth, and metabolism; body composition; enteral nutrition; supplements; parenteral nutrition; and respiratory outcomes. Conclusions Despite a large body of literature describing the role of growth and nutrition in the prevention of BPD, research is lacking with respect to interventions and management in the population with established BPD. Thus, organized approaches for clinical interventions and trials with respect to growth and nutrition in infants and young children with established BPD are needed. These studies should include multiple centers because of the small numbers of patients with BPD at each site.

Bronchopulmonary dysplasia (BPD) remains the most common late morbidity of preterm birth. Ongoing clinical care and research have largely focused on the pathogenesis and prevention of BPD in preterm infants. However, preterm infants who develop BPD have significant medical needs that persist throughout their neonatal intensive care unit course and continue post-discharge, including those associated with growth and nutrition. The objective of this manuscript was to provide a review on nutrition and growth in infants with established BPD after discharge from the hospital and to identify the knowledge and research gaps to provide direction for future studies.

Background Zinc deficiency is associated with poor growth in children without cystic fibrosis (CF), but its impact on growth in children with CF is unknown. Objective To determine the prevalence of low serum Zn (sZn) and its relationship with growth in the first 3 years of life in children with CF. Methods We utilized data from infants with CF who were enrolled in a longitudinal study of nutrition and lung health and had sZn measured as part of clinical care. Cross-sectional correlations between sZn levels and growth z scores were assessed by Pearson's correlation coefficient. To identify factors associated with sZn status and its association to longitudinal growth patterns, multiple regression analysis with repeated measures were performed using generalized estimating equations. Results A total of 106 sZn measurements from 53 infants were identified. Seventeen infants (32%) had intermittent Zn insufficiency, defined as at least one sZn z scores. However, analysis of longitudinal growth patterns revealed that weight- and length-for-age z scores in children with intermittent Zn insufficiency were lower during early infancy and their weight-for-length z scores at age 3 years were also lower compared to those who were always Zn sufficient. Conclusion Low sZn occurs in one-third of children with CF in the first 3 years of life. Cross-sectional and longitudinal analyses revealed discrepant associations between sZn and growth. Therefore, prospective studies are needed to understand the role of Zn in growth in CF.

Background Infants with a positive cystic fibrosis (CF) newborn screen, only one identified CFTR mutation (NBS+/1 mut), and an initial intermediate sweat chloride (30-59 mmol/L) should have repeat sweat chloride testing (SCT). However, the outcome of repeat SCT and the relationship between initial sweat Cl and subsequent CF diagnosis have not been reported. Objective The objective of this study was to analyze the outcomes of repeat SCT and subsequent CF diagnosis in NBS+/1 mut infants based on their initial sweat chloride concentration. Methods We retrospectively identified all infants born in Indiana from 2007 to 2017 with NBS+/1 mut and initial SCT in the intermediate range. For each infant, we recorded the initial and repeat SCT results and/or a final CF diagnosis. Results From 2007 through 2017 there were 2822 NBS+/1 mut infants of which 2613 (82%) had at least one SCT result. No infants with an initial SCT of 30-39 mmol/L were subsequently diagnosed with CF. Of the 31 infants with an initial SCT of 40-49 mmol/L, only 1 was subsequently diagnosed with CF. In contrast, 61% of those with SCTs of 50-59 mmol/L were later diagnosed with CF. Conclusion These results suggest that infants with a positive NBS for CF and one CFTR mutationwhose initial sweat chloride concentration is 50-59 mmol/L need to be monitored more closely forCF with strong consideration for earlier repeat SCTs and immediate genotyping

Asthma is a common obstructive lung disease in pediatric medical practice and encompasses a wide degree of severity. Other obstructive lung diseases encountered by pediatric pulmonary physicians include bronchopulmonary dysplasia, primary ciliary dyskinesia, non-cystic fibrosis bronchiectasis, and sickle cell disease. These diseases have a wide range of clinical phenotypes and disease severities which persist into adulthood. The following chapter provides best practices and recommendations in asthma and other obstructive lung diseases to maintain continued care and prevent loss to follow-up.

Objective To identify factors associated with neurodevelopmental impairment (NDI) in patients with bronchopulmonary dysplasia (BPD). Study design We identified 151 patients with moderate to severe BPD from 2010 to 2014 with complete Bayley Scales of Infant Development (BSID) scores at 24 months corrected age. We defined NDI as any diagnosis of cerebral palsy or >= 1 BSID composite scores of <80. Results The mean corrected age at BSID was 23 +/- 1 months; 18% had a cognitive score of <80, 37% had a communication score of <80, and 26% had a motor score of <80. Cerebral palsy was diagnosed in 22 patients (15%); 84 (56%) patients did not have NDI. Patients with NDI had lower birth weight, but there was no difference in gestational age at birth, severe intraventricular hemorrhage (IVH), necrotizing enterocolitis, or patent ductus arteriosus ligation compared with patients with no NDI. Ventilator days were greater in patients with NDI than in patients without NDI. More patients with NDI received furosemide and systemic corticosteroids and the hospital length of stay was longer than in patients with no NDI. Logistic regression modeling demonstrated that for every additional 100 g of birth weight the odds of NDI decreased by 35% and for every additional hospital day the odds of NDI increased by 1.3%. Conclusions In our cohort of patients with moderate to severe BPD, the majority had no NDI, and low birth weight and length of hospital stay were associated with increased risk of developing NDI. This finding suggests that there are potentially modifiable factors associated with better neurodevelopmental outcomes in patients with BPD that deserve further study.

Background: While there is a large body of evidence detailing the effects of secondhand smoke exposure (SHSe) in the general pediatric population, little was known until recently of the effects of SHSe in patients with cystic fibrosis (CF). Recent data from our large pediatric academic institution have shown associations with decreased growth, increased bacterial infections, poorer performance on pulmonary function tests, altered prostaglandin signaling, and more frequent hospitalizations in patients with CF and SHSe. However, only 10% of CF patients with SHSe …

HINTERGRUND: Arsentrioxid induziert die klinische Remission bei akuter Promyelozytenleukamie (APL) durch die intrazellulare Bildung von Oxyradikalen (ROS = reactive oxygen spezies). Da katecholaminproduzierende Neuroblastomzellen wahrend der Katecholaminsynthese schon von vorn herein hohen Oxyradikalkonzentrationen ausgesetzt sind, ist bei diesen Zellen eine im Vergleich zu anderen malignen Zellen hohere Empfindlichkeit fur Arsentrioxid zu erwarten. Auserdem kann vermutet werden, dass die Empfindlichkeit verschiedener Tumorzellen fur Arsentrioxid umgekehrt mit deren antioxidativer Kapazitat korreliert. Diese Hypothese wurde durch die folgenden Ergebnisse bestatigt. ERGEBNISSE: Das Wachstum der Neuroblastom-Zell-Linien LA-N-1, LA-N-5, SH-SY5Y und HSJD konnte durch Arsentrioxid in Konzentrationen, die mit klinisch erreichbaren Serumspiegeln bei APL-Patienten vergleichbar sind, deutlich gehemmt werden (ID 50: 2,8 µM, 4,0 µM, 5,3 µM und 5,0 µM respektive). Der wachstumshemmende Effekt korrelierte umgekehrt mit dem intrazellularen Gehalt an Glutathion, einem entscheidenden intrazellularen Antioxidanz. Im Gegensatz dazu waren die Mammakarzinom-Zell-Linie MDA-MB-231 und die Zell-Linie eines hepatozellularen Karzinoms Hep G2 hoch resistent gegen Arsentrioxid (ID 50: 10,0 µM, 8,0 µM respektive). BSO – ein spezifischer Inhibitor der Glutathionsynthese – konnte diese Resistenz komplett aufheben. SCHLUSSFOLGERUNG: Wir zeigten (a), dass Arsentrioxid aufgrund seiner ROS-bildenden Aktivitat ein viel versprechendes neues Medikament zur Behandlung des Neuroblastoms sein konnte und (b), BSO ein potenter Chemosensitizer fur maligne Zellen mit immanenter glutathionbedingter Resistenz gegen ROS-bildende Medikamente wie Arsentrioxid ist. BACKGROUND: Arsenic trioxide induces clinical remission in acute promyelocytic leukemia (APL) by the generation of intracellular reactive oxygen species (ROS). As neuroblastoma cells are already exposed to high levels of ROS during the synthesis of catecholamines a higher sensitivity of neuroblastoma cells for arsenic trioxide may be expected compared with other malignant cells. Moreover, it may be assumed that the sensitivity of different tumor cells for arsenic trioxide is inversely correlated with their radical scavenging capacity. This hypothesis has been confirmed by the following. RESULTS: Proliferation of the neuroblastoma cell lines LA-N-1, LA-N-5, SH-SY5Y and HSJD could be inhibited by arsenic trioxide concentrations, which are comparable with tolerable serum levels in APL-patients (50 % inhibitory concentration (ID 50): 2,8 µM, 4,0 µM, 5,3 µM and 5,0 µM respectively). The antiproliferative effect of arsenic trioxide did inversely correlate with the intracellular concentration of glutathione (GSH), which is the main ROS-scavenger. In contrast the breast carcinoma MDA-MB-231 and the hepatocellular carcinoma cell line Hep-G2 have been highly resistant against arsenic trioxide (ID 50: 10,0 µM, 8,0 µM resp.). This resistance could be completely reversed by buthionine sulfoximine which is a potent inhibitor of GSH-synthesis. CONCLUSION: We showed (a) that arsenic trioxide may be a promising new agent for neuroblastoma therapy due to its ROS-generating activity and (b) that buthionine sulfoximine is a potent chemosensitizer of malignant cells with GSH-mediated innate resistance against ROS-generating agents like arsenic trioxide.