Outcomes of infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension who required home ventilation.

BACKGROUND: To characterize a cohort of ventilator-dependent infants and children with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) and to describe their cardiorespiratory outcomes. METHODS: 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. RESULTS: Of the 154 subjects, 93 (60.4%) had PH and of those, 52 (55.9%) required PH-specific medications. The ages at tracheostomy, transition to home ventilator, and hospital discharge were older in those with PH. Most subjects were weaned off oxygen and liberated from the ventilator by 5 years of age, which did not occur later in subjects with PH. The mortality rate after initial discharge was 2.6%. CONCLUSIONS: The majority of infants with BPD-PH receiving chronic invasive ventilation at home survived after initial discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen and PH medications, ventilator liberation, and tracheostomy decannulation. While the presence of PH was not associated with later ventilator liberation or decannulation, the use of PH medications may be a marker of a more protracted disease trajectory. IMPACT STATEMENT: There is limited data on long-term outcomes of children with bronchopulmonary dysplasia (BPD) who receive chronic invasive ventilation at home, and no data on those with the comorbidity of pulmonary hypertension (PH). Almost all subjects with BPD-PH who were on chronic invasive ventilation at home survived after their initial hospital discharge. Subjects with BPD-PH improved over time as evidenced by weaning off oxygen, PH medications, liberation from the ventilator, and tracheostomy decannulation. The presence of PH did not result in later ventilator liberation or decannulation; however, the use of outpatient PH medications was associated with later ventilation liberation and decannulation.

Parental Report of Indoor Air Pollution Is Associated with Respiratory Morbidities in Bronchopulmonary Dysplasia.

OBJECTIVE: To determine the association between indoor air pollution and respiratory morbidities in children with bronchopulmonary dysplasia (BPD) recruited from the multicenter BPD Collaborative. STUDY DESIGN: A cross-sectional study was performed among participants <3 years old in the BPD Collaborative Outpatient Registry. Indoor air pollution was defined as any reported exposure to tobacco or marijuana smoke, electronic cigarette emissions, gas stoves, and/or wood stoves. Clinical data included acute care use and chronic respiratory symptoms in the past 4 weeks. RESULTS: A total of 1011 participants born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. More than 40% of participants were exposed to ≥1 source of indoor air pollution. The odds of reporting an emergency department visit (OR, 1.7; 95% CI, 1.18-2.45), antibiotic use (OR, 1.9; 95% CI, 1.12-3.21), or a systemic steroid course (OR, 2.18; 95% CI, 1.24-3.84) were significantly higher in participants reporting exposure to secondhand smoke (SHS) compared with those without SHS exposure. Participants reporting exposure to air pollution (not including SHS) also had a significantly greater odds (OR, 1.48; 95% CI, 1.08-2.03) of antibiotic use as well. Indoor air pollution exposure (including SHS) was not associated with chronic respiratory symptoms or rescue medication use. CONCLUSIONS: Exposure to indoor air pollution, especially SHS, was associated with acute respiratory morbidities, including emergency department visits, antibiotics for respiratory illnesses, and systemic steroid use.

The Legacy of the COVID-19 Pandemic: Impact on Infant and Maternal and Health from an Appalachian Academic Medical Center.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic period from 2020 to 2022 had a significant impact on maternal infant health with mothers impacted more than their infants. We questioned whether there have been any lingering effects from the pandemic. METHODS: We examined intermediate and long-term pandemic effects on maternal and neonatal outcomes before, during, and after the COVID-19 pandemic period. We reviewed mother-infant pairs from the following three epochs: (1) the pre-COVID-19 period, (2) the COVID-19 pandemic period, and (3) the post-pandemic period. The Case Mix Index (CMI) for the neonates from all three epochs were detailed. RESULTS: Post-pandemic, we noted a rising trend of LGA infants (10%) and an increase in SGA infants (13%). For women in 2023, we noted an increase in hypertension, preeclampsia, diabetes, and a higher BMI than in the pre-pandemic period. There have also been more congenital anomalies (9%), and neonatal CMI increased in the post-pandemic period. CONCLUSIONS: Well after the pandemic period, maternal-infant health continues to be affected. For women, the increase in hypertension and diabetes during pregnancy is concerning. For infants, being LGA or SGA may have long-term consequences. The post-pandemic increase in infants with congenital anomalies compared to the pre-pandemic era is an area that needs ongoing review.

A Scalable and Surfactant-Free Emulsion Method for Producing Microbeads from Varied Biomass Feedstocks.

Despite national and international regulations, plastic microbeads are still widely used in personal care and consumer products (PCCPs). These exfoliants and rheological modifiers cause significant microplastic pollution in natural aquatic environments. Microbeads from nonderivatized biomass like cellulose and lignin can offer a sustainable alternative to these nondegradable microplastics, but processing this biomass into microbeads is challenging due to limited viable solvents and high biomass solution viscosities. To produce biomass microbeads of the appropriate size range for PCCPs (ca. 200-800 µm diameter) with shapes and mechanical properties comparable to those of commercial plastic microbeads, we used a surfactant-free emulsion/precipitation method, mixing biomass solutions in 1-ethyl-3-methylimidazolium acetate (EMImAc) with various oils and precipitating with ethanol. While yield of microbeads within the target size range highly depends on purification conditions, optimized protocols led to >90% yield of cellulose microbeads. Kraft lignin was then successfully incorporated into beads at up to 20 wt %; however, higher lignin contents result in emulsion destabilization unless surfactant is added. Finally, the microbead shape and surface morphology can be tuned using oils of varying viscosities and interfacial tensions. Dripping measurements and pendant drop tensiometry confirmed that the higher affinity of cellulose for certain oil/IL interfaces largely controlled the observed surface morphology. This work thus outlines how biomass composition, oil viscosity, and interfacial properties can be altered to produce more sustainable microbeads for use in PCCPs, which have desirable mechanical properties and can be produced over a wide range of shapes and surface morphologies.

Factors associated with liberation from home mechanical ventilation and tracheostomy decannulation in infants and children with severe bronchopulmonary dysplasia.

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.

Determinants of microbiome composition: Insights from free-ranging hybrid zebras (Equus quagga × grevyi).

The composition of mammalian gut microbiomes is highly conserved within species, yet the mechanisms by which microbiome composition is transmitted and maintained within lineages of wild animals remain unclear. Mutually compatible hypotheses exist, including that microbiome fidelity results from inherited dietary habits, shared environmental exposure, morphophysiological filtering and/or maternal effects. Interspecific hybrids are a promising system in which to interrogate the determinants of microbiome composition because hybrids can decouple traits and processes that are otherwise co-inherited in their parent species. We used a population of free-living hybrid zebras (Equus quagga × grevyi) in Kenya to evaluate the roles of these four mechanisms in regulating microbiome composition. We analysed faecal DNA for both the trnL-P6 and the 16S rRNA V4 region to characterize the diets and microbiomes of the hybrid zebra and of their parent species, plains zebra (E. quagga) and Grevy's zebra (E. grevyi). We found that both diet and microbiome composition clustered by species, and that hybrid diets and microbiomes were largely nested within those of the maternal species, plains zebra. Hybrid microbiomes were less variable than those of either parent species where they co-occurred. Diet and microbiome composition were strongly correlated, although the strength of this correlation varied between species. These patterns are most consistent with the maternal-effects hypothesis, somewhat consistent with the diet hypothesis, and largely inconsistent with the environmental-sourcing and morphophysiological-filtering hypotheses. Maternal transmittance likely operates in conjunction with inherited feeding habits to conserve microbiome composition within species.

Managing established bronchopulmonary dysplasia without using routine blood gas measurements.

OBJECTIVE: Routine blood gas measurements are common in infants with severe bronchopulmonary dysplasia (sBPD) and are a noxious stimulus. We developed a guideline-driven approach to evaluate the care of infants with sBPD without routine blood gas sampling in the chronic phase of NICU care (after diagnosis at 36 weeks PMA). STUDY DESIGN: We examined blood gas utilization and outcomes in our sBPD inpatient care unit using data collected between 2014 and 2020. RESULTS: 485 sBPD infants met inclusion criteria, and 303 (62%) never had a blood gas obtained after 36 weeks PMA. In infants who had blood gas measurements, the median number of total blood gases per patient was only 4 (IQR 1-10). We did not identify adverse effects on hospital outcomes in patients without routine blood gas measurements. CONCLUSIONS: We found that patients with established BPD could be managed without routine blood gas analyses after 36 weeks PMA.

Airway disease decreases the therapeutic potential of epithelial stem cells.

BACKGORUND: Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown. METHODS: In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients. RESULTS: Our findings revealed that basal cell recovery and frequency did not vary by age or region. At passage 1, all samples produced enough cells to cellularize a 3.5 by 0.5 cm2 graft scaffold at low cell density (~ 7000 cells/cm2), and 43.75% could cellularize a scaffold at high cell density (~ 100,000 cells/cm2). At passage 2, all samples produced the number of cells required for both recellularization models. Further evaluation revealed that six pediatric samples (11%) and three (50%) adult samples contained basal cells with a squamous basal phenotype. These cells did not form a polarized epithelium or produce differentiated secretory or ciliated cells. In the pediatric population, the squamous basal cell phenotype was associated with degree of prematurity (< 28 weeks, 64% vs. 13%, p = 0.02), significant pulmonary history (83% vs. 34%, p = 0.02), specifically with bronchopulmonary dysplasia (67% vs. 19%, p = 0.01), and patients who underwent previous tracheostomy (67% vs. 23%, p = 0.03). CONCLUSIONS: In summary, screening high-risk pediatric or adult population based on clinical risk factors and laboratory findings could define appropriate candidates for airway reconstruction with tracheal scaffolds. LEVEL OF EVIDENCE: Level III Cohort study.

Number of children in the household influences respiratory morbidities in children with bronchopulmonary dysplasia in the outpatient setting.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD. METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations. RESULTS: The mean gestational age of the study population was 26.5 ± 2.2 weeks and most subjects (69.1%) had severe BPD. The mean number of children in households (including the subject) was 2.1 ± 1.3 children. Each additional child in the household was associated with a 13% increased risk for hospital admission, 13% increased risk for antibiotic use for respiratory illnesses, 10% increased risk for coughing/wheezing/shortness of breath, 14% increased risk for nighttime symptoms, and 18% increased risk for rescue medication use. Additional analyses found that the increased risks were most prominent when there were three or more other children in the household. CONCLUSIONS: We observed that additional children in the household were a risk factor for adverse respiratory outcomes. We speculate that secondary person-to-person transmission of respiratory viral infections drives this finding. While this risk factor is not easily modified, measures do exist to mitigate this disease burden. Further studies are needed to define best practices for mitigating this risk associated with household viral transmission.

Nutritional Needs of the Infant with Bronchopulmonary Dysplasia.

Growth failure is a common problem in infants with established bronchopulmonary dysplasia (BPD). Suboptimal growth for infants with BPD is associated with unfavorable respiratory and neurodevelopmental outcomes; however, high-quality evidence to support best nutritional practices are limited for this vulnerable patient population. Consequently, there exists a wide variation in the provision of nutritional care and monitoring of growth for infants with BPD. Other neonatal populations at risk for growth failure, such as infants with congenital heart disease, have demonstrated improved growth outcomes with the creation and compliance of clinical protocols to guide nutritional management. Developing clinical protocols to guide nutritional management for infants with BPD may similarly improve long-term outcomes. Given the absence of high-quality trials to guide nutritional practice in infants with BPD, the best available evidence of systematic reviews and clinical recommendations can be applied to optimize growth and decrease variation in the care of these infants.

Multidisciplinary bronchopulmonary dysplasia care.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in neonates and infants, which often presents with multisystem organ involvement, co-morbidities, and prolonged hospital stays. Therefore, a multidisciplinary chronic care approach is needed in the severest forms of BPD to optimize outcomes. However, this approach can be challenging to implement. The objective of this article is to review and synthesize the available literature regarding multidisciplinary care in infants and children with established BPD, and to provide a framework that can guide clinical practice and future research. AREAS COVERED: A literature search was conducted using Ovid MEDLINE, CINAHL, and Embase and several components of multidisciplinary management of BPD were identified and reviewed, including chronic care, team development, team members, discharge planning, and outpatient care. EXPERT OPINION: Establishing a core multidisciplinary group familiar with the chronicity of established BPD is recommended as best practice for this population. Acknowledging this is not feasible for all individual centers, it is important for clinical practice and future research to focus on the development and incorporation of national consulting services, telemedicine, and educational resources.

Respiratory management of established severe bronchopulmonary dysplasia.

Respiratory management of infants with established severe BPD is difficult and there is little evidence upon which to base decisions. Nonetheless, the physiology of severe BPD is well described with a predominantly obstructive pattern. This pulmonary dysfunction results in prolonged exhalatory time constants and thus ventilator management must be focused on maintaining adequate oxygenation and ventilation through achieving full exhalation. This approach is often difficult to maintain in acute care settings and a culture of chronic care focused on slow change and steady progress is imperative. Once respiratory stability is achieved, the focus should shift to growth and development and avoidance of care practices and medications that impair neurodevelopment.

Tracheostomy in Severe Bronchopulmonary Dysplasia-How to Decide in the Absence of Evidence.

Infants with the most severe forms of bronchopulmonary dysplasia (BPD) may require long-term invasive positive pressure ventilation for survival, therefore necessitating tracheostomy. Although life-saving, tracheostomy has also been associated with high mortality, postoperative complications, high readmission rates, neurodevelopmental impairment, and significant caregiver burden, making it a highly complex and challenging decision. However, for some infants tracheostomy may be necessary for survival and the only way to facilitate a timely and safe transition home. The specific indications for tracheostomy and the timing of the procedure in infants with severe BPD are currently unknown. Hence, centers and clinicians display broad variations in practice with regard to tracheostomy, which presents barriers to designing evidence-generating studies and establishing a consensus approach. As the incidence of severe BPD continues to rise, the question remains, how do we decide on tracheostomy to provide optimal outcomes for these patients?

When Potential Allies and Targets Do (and Do Not) Confront Anti-Asian Prejudice: Reactions to Blatant and Subtle Prejudice During the COVID-19 Pandemic.

Anti-Asian xenophobia has exploded during the COVID-19 pandemic, after U.S. political leaders promoted anti-Asian rhetoric from its start. Confronting prejudice interrupts future perpetration of such prejudice, but confronting prejudice can only occur to the extent actions are first attributed to prejudice. Bystanders may attribute less prejudice to speech about the "Chinese Virus" than to more blatant stereotype expression, for example, and therefore be less vehement in their confrontations. Across two studies, we examined the impact of anti-Asian prejudice type (blatant, subtle, or no prejudice) and bystander race/ethnicity (White or Asian American/Pacific Islander [AAPI]), on prejudice attribution, willingness to confront, actual confrontation, and confrontation vehemence. In the context of a hiring manager justifying rejection of a Chinese applicant, we predicted that blatant prejudice would be detected and confronted most willingly, and subtle prejudice more willingly than no prejudice, and that prejudice detection would mediate the relationship between prejudice type and willingness to confront. Further, we expected AAPI bystanders to detect anti-Asian prejudice more readily than White bystanders, but to confront at lower rates, with actual confrontations being more vehement following blatant (relative to subtle or no) prejudice. Analyses were conducted using SPSS 27 and the PROCESS v4.1 macro, controlling for potential confounds such as political orientation and individual-level prejudice (expressed or perceived). Results of both studies (n = 142 [Study 1], n = 274 [Study 2]) supported hypotheses, except in Study 1 bystanders exposed to subtle prejudice were no more willing to confront than no-prejudice controls. Results of exploratory analyses indicated that attribution to prejudice was the primary obstacle to confrontation following subtle prejudice, whereas action taking was the primary obstacle following blatant prejudice. This research underscores the need for interventions to increase detection of all forms of anti-Asian prejudice and to provide would-be confronters with effective confrontation tools.

Igneous meteorites suggest Aluminium-26 heterogeneity in the early Solar Nebula.

The short-lived radionuclide aluminium-26 (26Al) isotope is a major heat source for early planetary melting. The aluminium-26 - magnesium-26 (26Al-26Mg) decay system also serves as a high-resolution relative chronometer. In both cases, however, it is critical to establish whether 26Al was homogeneously or heterogeneously distributed throughout the solar nebula. Here we report a precise lead-207 - lead-206 (207Pb-206Pb) isotopic age of 4565.56 ± 0.12 million years (Ma) for the andesitic achondrite Erg Chech 002. Our analysis, in conjunction with published 26Al-26Mg data, reveals that the initial 26Al/27Al in the source material of this achondrite was notably higher than in various other well-preserved and precisely dated achondrites. Here we demonstrate that the current data clearly indicate spatial heterogeneity of 26Al by a factor of 3-4 in the precursor molecular cloud or the protoplanetary disk of the Solar System, likely associated with the late infall of stellar materials with freshly synthesized radionuclides.

Nutritional Strategies to Optimize Outcomes among Infants with Congenital Heart Disease.

Growth failure is common among infants with congenital heart disease (CHD), affecting approximately half of all infants with CHD. Achieving good growth is difficult secondary to both cardiac and noncardiac factors that affect energy expenditure and nutritional intake. Growth failure is associated with poor outcomes, including mortality, prolonged length of hospital stay, delayed cardiac surgery, postoperative complications, and neurodevelopmental delay. Clinical practice varies widely when it comes to how nutrition is managed in these infants, with varying approaches to enteral feeding initiation, advancement, and discontinuation. This variation persists despite several practice guidelines that have been created in recent years to guide nutritional care. Standardized feeding protocols have been proven to reduce growth failure and improve outcomes for this patient population. Centers and clinicians should be encouraged to adopt existing guidelines, or create their own from evidence-based literature, to improve growth and outcomes for infants with CHD.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

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.

A review and guide to nutritional care of the infant with established bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains the most common long-term morbidity of premature birth, and the incidence of BPD is not declining despite medical advancements. Infants with BPD are at high risk for postnatal growth failure and are often treated with therapies that suppress growth. Additionally, these infants may display excess weight gain relative to linear growth. Optimal growth and nutrition are needed to promote lung growth and repair, improve long-term pulmonary function, and improve neurodevelopmental outcomes. Linear growth in particular has been associated with favorable outcomes yet can be difficult to achieve in these patients. While there has been a significant clinical and research focus regarding BPD prevention and early preterm nutrition, there is a lack of literature regarding nutritional care of the infant with established BPD. There is even less information regarding how nutritional needs change as BPD evolves from an acute to chronic disease. This article reviews the current literature regarding nutritional challenges, enteral nutrition management, and monitoring for patients with established BPD. Additionally, this article provides a practical framework for interdisciplinary nutritional care based on our clinical experience at the Comprehensive Center for Bronchopulmonary Dysplasia.