Ambient Air Pollution and Outpatient Morbidities in Bronchopulmonary Dysplasia.

Rationale: Bronchopulmonary dysplasia (BPD) is the most common long-term complication of prematurity. Although socioeconomic status is associated with BPD morbidities, the drivers of this association are poorly understood. In the United States, ambient air pollution (AAP) exposure is linked to both race/ethnicity and socioeconomic status. Furthermore, AAP exposure is known to have a detrimental effect on respiratory health in children. Objectives: To assess if AAP exposure is linked to BPD morbidity in the outpatient setting. Methods: Participants with BPD were recruited from outpatient clinics at Johns Hopkins University and the Children's Hospital of Philadelphia between 2008 and 2021 (N = 800) and divided into low, moderate, and high AAP exposure groups, based on publicly available U.S. Environmental Protection Agency data. Clinical data were obtained by chart review and caregiver questionnaires. Results: Non-White race, home ventilator use, and lower median household income were associated with higher degrees of air pollution exposure. After adjustment for these factors, moderate and high air pollution exposure were associated with requiring systemic steroids (odds ratio, 1.78 and 2.17, respectively) compared with low air pollution. Similarly, high air pollution exposure was associated with emergency department visits (odds ratio, 1.59). Conclusions: This study demonstrates an association between AAP exposure and BPD morbidity after initial hospital discharge. AAP exposure was closely linked to race and median household income. As such, it supports the notion that AAP exposure may be contributing to health disparities in BPD outcomes. Further studies directly measuring exposure and establishing a link between biomarkers of exposure and outcomes are prerequisites to developing targeted interventions protecting this vulnerable population.

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.

Patterns of early life somatic growth in infants and children with a history of chronic lung disease of prematurity.

OBJECTIVE: Preterm infants, and especially those with additional comorbidities, are at risk of early life growth failure, which may impact postnatal lung growth and attainment of peak lung function. However, little is known about the early life growth patterns of those with chronic lung disease. The goal of this study was to describe the patterns appreciated in this population and their association with certain clinical characteristics. STUDY DESIGN: Demographic, clinical characteristics, and somatic growth parameters between birth and 3 years were retrospectively reviewed for a cohort of children (n = 616) recruited from an outpatient pulmonary clinic. Group-based trajectory modeling was used to identify unique longitudinal trajectories for each growth parameter. Demographic and clinical characteristics were compared using nonparametric analysis. RESULTS: Four distinct trajectories were appreciated in all three somatic growth domains (weight, length, and weight-for-length), which demonstrated a sizable proportion of subjects with a z-score below zero at 36 months of age, suggesting that the traditional preterm paradigm of "catch-up" growth may not be accurate for this population. CONCLUSIONS: Children with a history of chronic lung disease begin life with somatic growth measurements well below their term peers and display heterogeneous patterns of weight and length growth through the first 3 years of life. Future studies should focus on further understanding the relationship between somatic growth and respiratory outcomes in this population, which will ideally allow for the use of somatic growth measures as surrogate markers to identify individuals at the highest risk of postnatal growth failure and poor respiratory outcomes.

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.

Validation of an outpatient questionnaire for bronchopulmonary dysplasia control.

INTRODUCTION: Despite 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. METHODS: Data 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. RESULTS: Based 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. CONCLUSION: Our 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.

Outpatient respiratory outcomes in children with BPD on supplemental oxygen.

INTRODUCTION: Preterm children with bronchopulmonary dysplasia (BPD) frequently require supplemental oxygen in the outpatient setting. In this study, we sought to determine patient characteristics and demographics associated with need for supplemental oxygen at initial hospital discharge, timing to supplemental oxygen liberation, and associations between level of supplemental oxygen and likelihood of respiratory symptoms and acute care usage in the outpatient setting. METHODS: A retrospective analysis of subjects with BPD on supplemental oxygen (O2 ) was performed. Subjects were recruited from outpatient clinics at Johns Hopkins University and the Children's Hospital of Philadelphia between 2008 and 2021. Data were obtained by chart review and caregiver questionnaires. RESULTS: Children with BPD receiving ≥1 L of O2 were more likely to have severe BPD, pulmonary hypertension, and be older at initial hospital discharge. Children discharged on higher levels of supplemental O2 were slower to wean to room air compared to lower O2 groups (p < 0.001). Additionally, weaning off supplemental O2 in the outpatient setting was delayed in children with gastrostomy tubes and those prescribed inhaled corticosteroids, on public insurance or with lower household incomes. Level of supplemental O2 at discharge did not influence outpatient acute care usage or respiratory symptoms. CONCLUSION: BPD severity and level of supplemental oxygen use at discharge did not correlate with subsequent acute care usage or respiratory symptoms in children with BPD. Weaning of O2 however was significantly associated with socioeconomic status and respiratory medication use, contributing to the variability in O2 weaning in the outpatient setting.

Inpatient albuterol spacing as an indicator of discharge readiness.

INTRODUCTION: In children admitted for asthma exacerbation, multiple evidence-based, clinical practice guidelines exist to identify readiness for discharge. At many institutions, weaning of albuterol is part of the discharge process, though presently there is limited evidence to guide best practice. We sought to determine how many children required escalation of care once placed on every 4-h dosing of albuterol. METHODS: We performed a consecutive case series of pediatric patients between 5 and 18 years of age admitted to a single tertiary care center's pediatric hospitalist service between April 2015 and April 2018 with a discharge diagnosis of asthma. Patients admitted to the intensive care unit (PICU) or a subspecialty service were excluded, as has been done previously. Time between albuterol administrations was tracked. "Treatment escalation" was defined as when a patient required more frequent albuterol more dosing after previously tolerating albuterol doses separated by more than 3.5 h. RESULTS: A total of 331 patients met inclusion criteria; 136 were female (41.1%), and the average age was 8.8 years. Twenty-six of the 331 patients (7.8%) required escalation of albuterol therapy. Eleven patients returned to the emergency department (ED) following discharge, 2 of which had experienced treatment escalation while admitted. CONCLUSIONS: Our case series showed that most patients were safe to discharge after spacing albuterol treatments to 4 h, with few returns to the ED and readmissions. Albuterol spacing to every 4 h once appears to be a reasonable discharge criterion, but future studies are needed to determine if this is a safe and efficient.

Mortality in Outpatients with Bronchopulmonary Dysplasia.

OBJECTIVES: To study the demographic and clinical characteristics of preterm infants with bronchopulmonary dysplasia (BPD) to identify the factors most strongly predictive of outpatient mortality, with the goal of identifying those individuals at greatest risk. STUDY DESIGN: Demographic and clinical characteristics were retrospectively reviewed for 862 subjects recruited from an outpatient BPD clinic. Characteristics of the deceased and living participants were compared using nonparametric analysis. Regression analysis was performed to identify factors associated with mortality. RESULTS: Of the 862 subjects, 13 (1.5%) died during follow-up, for an overall mortality rate of approximately 15.1 deaths per 1000 subjects. Two patients died in the postneonatal period (annual mortality incidence, 369.9 per 100 000), 9 died between age 1 and 4 years (annual mortality incidence, 310.2 per 100 000), and 2 died between age of 5 and 14 years (annual mortality incidence, 71.4 per 100 000). After adjusting for gestational age and BPD severity, mortality was found to be associated with the amount of supplemental oxygen required at discharge from the neonatal intensive care unit (adjusted hazard ratio [aHR], 4.10; P = .001), presence of a gastrostomy tube (aHR, 8.13; P = .012), and presence of a cerebrospinal fluid (CSF) shunt (aHR, 4.31; P = .021). CONCLUSIONS: The incidence of mortality among preterm infants with BPD is substantially higher than that seen in the general population. The need for greater amounts of home supplemental oxygen and the presence of a gastrostomy tube or CSF shunt were associated with an increased risk of postdischarge mortality. Future studies should focus on clarifying risk factors for the development of severe disease to allow for early identification and treatment of those at highest risk.

Family history of asthma influences outpatient respiratory outcomes in children with BPD.

INTRODUCTION: Preterm children with bronchopulmonary dysplasia (BPD) are at increased risk for intermittent and chronic respiratory symptoms during childhood and adult life. Identifying children at higher risk for respiratory morbidities in the outpatient setting could help improve long-term outcomes. In this study, we hypothesized that a family history of asthma (FHA) is a risk factor for higher acute care usage and respiratory symptoms in preterm infants/children with BPD, following initial discharge home. METHODS: Subjects were recruited from the Johns Hopkins Bronchopulmonary Dysplasia outpatient clinic between January 2008 and February 2020 (n = 827). Surveys were administered to caregivers and demographics and clinical characteristics were obtained through chart review. RESULTS: Demographic features associated with FHA included public health insurance, lower median household income, and nonwhite race. Children with FHA had higher odds of emergency department (ED) visits, systemic steroid use, nighttime respiratory symptoms, and activity limitations. There was no association between FHA and BPD severity. CONCLUSION: This study found that children with BPD and FHA were more likely to have respiratory symptoms and acute care usage during the first 3 years of life and that FHA was associated with lower socioeconomic status. Although there was no association between FHA and BPD severity, FHA could predict an increased likelihood of both ED visits and need for systemic steroids in infants/children with BPD followed in the outpatient setting.

Influences of environmental exposures on preterm lung disease.

Introduction: Environmental factors play a critical role in the progression or resolution of chronic respiratory diseases. However, studies are limited on the impact of environmental risk factors on individuals born prematurely with lung disease after they leave the neonatal intensive care unit and are discharged into the home environment.Areas covered: In this review, we cover current knowledge of environmental exposures that impact outcomes of preterm respiratory disease, including air pollution, infections, and disparities. The limited data do suggest that certain exposures should be avoided and there are potential preventative strategies for other exposures. There is a need for additional research outside the neonatal intensive care unit that focuses on individual and community-level factors that affect long-term outcomes.Expert opinion: Preterm respiratory disease can impose a significant burden on infants, children, and young adults born prematurely, but may improve for many individuals over time. In this review, we outline the exposures that may potentially hasten, delay, or prevent resolution of lung injury in preterm children.

Predictors of pulmonary function at 6 years of age in infants with bronchopulmonary dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth and the most common cause of chronic lung disease in infancy. Previous studies have shown that children with a history of BPD have impaired lung function in childhood compared to their term counterparts. However, little is known about potential modifiable factors that alter lung function trajectories and subsequent respiratory morbidity in this population. OBJECTIVES: To identify potential modifiable risk factors for the development of impaired lung function in patients with a history of prematurity and bronchopulmonary dysplasia. METHODS: Growth parameters (birth, 2 years old, 6 years old) and pulmonary function testing (6 years old) were retrospectively reviewed for subjects (n = 598) recruited from an outpatient BPD clinic who were born ≤36 weeks gestation and were ≥5 years of age. RESULTS: Of the 598 recruited subjects, 88 (14.7%) performed adequate pulmonary function testing at approximately 6 years of age. The mean forced expiratory volume in 1 s global lung initiative (GLI) Z-score was -1.31 with lower values associated with Nissen fundoplication. The mean forced vital capacity GLI Z-score was -0.72 with lower values associated with higher amounts of oxygen required at time of initial hospital discharge and Nissen fundoplication. CONCLUSION: Our study found that children with BPD have lower predicted lung function values. Although growth parameters at age 2 and 6 years did not correlate with lung function values at 6 years of age; use and greater requirement for supplemental oxygen and the presence of a Nissen fundoplication at discharge were associated with lower lung function. Prospective studies should focus on identifying modifiable risk factors that could minimize the impact of BPD on later lung function.

Ivacaftor for the treatment of cystic fibrosis in children under six years of age.

Introduction: Cystic fibrosis (CF) results from aberrant ion transport due to abnormalities or absence of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride transporter that resides on the apical surface of epithelial cells. A novel class of medications, known as CFTR modulators, specifically target the abnormal protein.Areas covered: Ivacaftor increases the open probability of CFTR located on the cell surface, leading to enhanced chloride transport, and has been shown to improve lung function, weight, and quality of life. We reviewed the sentinel studies that lead to the approval of the use of ivacaftor in people with CF age six months and older with at least one CFTR gene mutation that is responsive to ivacaftor based on clinical trial and/or in vitro data. Children with CF have the greatest potential to benefit from CFTR modulator therapy when it is initiated prior to the development of permanent damage; however, challenges remain regarding use of ivacaftor in the youngest pediatric population.Expert opinion: Ivacaftor is safe and effective CFTR modulator that can be prescribed in children over six months of age with at least one CFTR gene mutation that is responsive to ivacaftor.