Gangaram Akangire

Background/Objectives: To characterize sedative and analgesic use in NICU patients with grade 3 bronchopulmonary dysplasia (BPD) in relation to respiratory support and neurodevelopmental therapies. Subjects/Methods: Point-prevalence survey across 22 NICUs of infants <24 months corrected age with grade 3 BPD who had never been discharged. Exclusions included recent sepsis, tracheostomy, or major surgery. Data were analyzed descriptively. Results: Among 141 infants, 97 (69%) received ≥1 sedative within 48 hours; 73 (75%) received multiple (mean 2.8 ± 1.6). Alpha-agonizts (n=67) and benzodiazepines (n=65) were most common, with 27 infants receiving an alpha-agonist, opioid, and benzodiazepine combination. Sedative exposure and medication count correlated with higher respiratory support (p<0.001) and FiO₂ (r=0.28, p<0.01). Sedation was associated with fewer completed therapy sessions (z=3.3, p<0.001). Conclusion: Sedation and polypharmacy were frequent among infants with severe BPD and linked to reduced therapy participation, highlighting the need to assess prescribing rationale and neurodevelopmental impacts.

Bronchopulmonary dysplasia (BPD) remains a debilitating disease in premature infants. The chronic pathogenesis of BPD with complex prenatal and postnatal programming challenges attempts at precisely defining or treating disease. While existing BPD definitions categorize disease severity, a lack of consideration of disease heterogeneity and endotypes has contributed to the failure of clinical trials to improve BPD outcomes. Recent studies have used advanced lung imaging techniques, echocardiography, and lung function tests to identify airway, parenchymal, and vascular BPD endotypes. These endotypes carry different prognoses and require endotype-specific treatment strategies to optimize infant outcomes. In this Review, we focus on the pathogenic mechanisms that specify individual BPD endotypes and discuss how combining biomarkers, functional studies, and artificial intelligence–based characterization of endotypes can inform precision therapies for BPD.

Objectives: To characterize an observational cohort of ventilator‐dependent infants and children with bronchopulmonary dysplasia (BPD) with or without tracheobronchomalacia (TBM) and determine the impact of TBM on the need for ventilator support, liberation from the ventilator and tracheostomy decannulation.Methods: Demographics and clinical outcomes were obtained by retrospective review from 12 centers participating in the outpatient BPD Collaborative registry. The cohort consisted of infants born between 2016 and 2021 who were dependent on invasive mechanical ventilation at home. The respiratory outcomes of those infants with TBM were compared to those who did not have TBM.Results: There were 154 subjects included and about half (48.7%) had documented TBM. Both the TBM and non‐TBM groups had similar demographic characteristics and respiratory outcomes. However, the non‐TBM were found to have lower mean birth weight (673 vs. 832 grams; p = 0.006), higher likelihood of having Nissen fundoplication (34.2% vs. 12.2%; p = 0.006) and higher use of diuretics (59.2% vs. 37.3%; p = 0.007). Both groups were similar in terms of ventilator requirements, timing of liberation from the ventilator, and rate of decannulation.Conclusions: The presence of TBM in ventilator‐dependent infants with BPD did not affect ventilator support needs, liberation from the ventilator and the rate of tracheostomy decannulation. We speculate that the relative contributions of the other components of BPD disease may play critical roles in determining the need for tracheostomy and their ultimate respiratory outcomes. A prospective multicenter study to assess the impact of TBM in severe BPD is urgently needed.

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.

Objective: To compare the accuracy of three newly proposed definitions of bronchopulmonary dysplasia (BPD) in predicting outcomes, and to assess the impact of BPD phenotypes (large airway vs. parenchymal vs. vascular disease) on BPD outcomes. Study Design: Retrospective chart review of 100 infants with severe BPD discharged from a Children’s hospital between 2020-2021. Multivariable models evaluated the associations between BPD definitions and phenotypes with tracheostomy and death. Result: Jensen’s and BPD collaborative criteria best predicted outcomes associated with tracheostomy and/or death (p < 0.001). Among the three BPD phenotypes, large airway disease independently predicted death or tracheostomy (OR 10.5, 95% CI 1.6, 68.1). The combination of all three phenotypes also predicted death or tracheostomy (OR 9.8, 95% CI 1.0, 93.5). Conclusion: Newly proposed definitions of BPD better predict outcomes compared to the 2001 NIH definition with BPD phenotypes impacting mortality and short-term outcomes. These data may be useful for counseling families and developing phenotype-based individualized treatment plans.

Objective To compare the cognitive, language and motor scores of infants with severe BPD exposed to postnatal corticosteroids (PCS) and had early (ET), late (LT) or no tracheostomy (NT). Methods Retrospective study was designed to compare the developmental outcomes of 71 infants born between 2010 and 2017 with severe BPD exposed to PCS and had ET (≤122 days), LT (>122 days), or NT. Results Cognitive scores were lower in LT versus NT and ET (p = 0.050); motor scores were worse in LT versus NT and ET (p = 0.004). Dexamethasone use was higher in LT versus NT and ET (p = 0.040). Adjusted for PCS, odds for major cognitive impairment were 90% less in ET versus LT. Trend for improved language and motor outcomes was seen in ET versus LT. Conclusion Infants with severe BPD exposed to PCS and had ET had significantly better cognitive, and trend toward improved language and motor outcomes.

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.

In recent years, with increased survival of infants with severe bronchopulmonary dysplasia (BPD), long term ventilation due to severe BPD has increased and become the most common indication for tracheostomy in infants less than one year of age. Evidence shows that tracheostomy in severe BPD may improve short- and long-term respiratory and neurodevelopmental outcomes. However, there is significant variation among centers in the indication, timing, intensive care management, and follow-up care after hospital discharge of infants with severe BPD who received tracheostomy for chronic ventilation. The timing of liberation from the ventilator, odds of decannulation, rate of rehospitalization, growth, and neurodevelopment are all clinically important outcomes that can guide both clinicians and parents to make a well-informed decision when choosing tracheostomy and long-term assisted ventilation for infants with severe BPD. This review summarizes the current literature regarding the indications and timing of tracheostomy placement in infants with severe BPD, highlights center variability in both intensive care and outpatient follow-up settings, and describes outcomes of infants with severe BPD who received tracheostomy.

Objective: To describe the survival rate, timing of liberation from the ventilator, and factors favorable for decannulation among infants with severe bronchopulmonary dysplasia (sBPD) who received tracheostomy.Methods: Demographics and clinical outcomes were obtained through retrospective chart review of 98 infants with sBPD who were born between 2004 and 2017, received tracheostomy at <1 year of age, and were followed in the Infant Tracheostomy and Home Ventilator clinic up to 4 years of age.Results: The number of infants with sBPD who received tracheostomy increased significantly over the study period. The median age at tracheostomy was 4 months (IQR 3, 5) or 43 weeks corrected gestational age; the median age at NICU discharge was 7 months (IQR 6, 9). At 48 months of age, all subjects had been liberated from the ventilator, at a median age of 24 months (IQR 18, 29); 52% had been decannulated with a median age at decannulation of 32 months (IQR 26, 39). Only 1 (1%) infant died. Multivariate logistic regression showed infants who were White, liberated from the ventilator by 24 months of age and have public insurance had significantly greater odds of being decannulated by 48 months of age. Tracheobronchomalacia was associated with decreased odds of decannulation.Conclusion: Infants with sBPD who received tracheostomy had an excellent survival rate. Liberation from home ventilation and decannulation are likely to occur by 4 years of age.