OBJECTIVE:To examine the demographic, clinical, and environmental characteristics of children with bronchopulmonary dysplasia (BPD) associated with respiratory readmissions. STUDY DESIGN:Demographic and clinical data were obtained from children with BPD recruited from 15 centers participating in the BPD Collaborative between 2018 and 2025. Subjects with any hospital readmission for respiratory reasons were compared with children not readmitted as assessed by questionnaires obtained at clinic visits during the first 3 years of life. Clustered regression models were used to identify variables associated with readmission. Secondary analyses were performed to identify factors associated with a higher number (≥2) of readmissions. RESULTS:There were 1615 participants who met inclusion criteria with a mean age of 9.4 ± 7.5 months at recruitment. During the study period, 352 (21.8%) had at least 1 readmission and 1263 had no reported readmission. In multivariable models, an increased likelihood of readmission was associated with a shorter initial neonatal intensive care unit hospitalization, use of a home ventilator, prescription of reflux medications, daycare attendance, and lower BPD control score. CONCLUSIONS:In young children with BPD, markers of medical complexity, such as home ventilator use for chronic respiratory failure and gastroesophageal reflux, were associated with a high likelihood of respiratory readmissions. Other potentially modifiable factors associated with readmissions include daycare attendance and respiratory symptom control. BPD severity was not associated with readmission risk. Identifying risk factors for respiratory readmission in the outpatient setting will help healthcare providers to provide targeted anticipatory guidance.

BACKGROUND:To assess whether human milk consumption after neonatal intensive care unit (NICU) discharge is associated with outpatient respiratory outcomes in infants and children with bronchopulmonary dysplasia (BPD). METHODS:We conducted a retrospective longitudinal cohort study of children under 2 years followed in outpatient BPD clinics. Participants were categorized by post-NICU human milk exposure (any vs. none). Caregiver questionnaires assessed the presence and frequency of chronic respiratory symptoms and acute care usage. Baseline characteristics were compared descriptively, and logistic regression with clustering by subject evaluated associations between human milk intake and outcomes. RESULTS:Among 1731 children, 445 (25.7%) received human milk after NICU discharge, and 1286 (74.3%) did not. After adjusting for potential confounders, human milk consumption was associated with lower odds of sick (OR: 0.65, p = 0.006) and emergency department visits (OR: 0.66, p = 0.015), antibiotic (OR: 0.58, p = 0.005) and steroid prescriptions (OR: 0.46, p < 0.001), and beta-agonist use in the prior 3 months (OR: 0.69, p = 0.008). CONCLUSIONS:In our multicenter cohort of children with BPD, post-NICU human milk consumption was associated with decreased parent-reported acute healthcare utilization and chronic respiratory symptoms, supporting its role as a modifiable risk factor that may improve respiratory outcomes in children with BPD. IMPACT:Human milk has been shown to decrease the incidence of bronchopulmonary dysplasia (BPD); however, limited data exist on the role of human milk intake after NICU discharge and its effect on long-term outpatient respiratory outcomes. Our findings demonstrate that post-NICU human milk intake is associated with decreased acute care usage and chronic respiratory symptoms in children with BPD, suggesting that human milk consumption is potentially a modifiable risk factor to improve outcomes. Further investigation using quantitative time-adjusted analyses, evaluating long-term respiratory consequences, and addressing barriers to use is needed to better define the role of human milk in this population.

INTRODUCTION:Lung-function outcomes among preterm-born children referred for pulmonology care are highly heterogeneous, and early determinants remain incompletely defined. We aimed to identify early-life factors associated with school-age lung function after preterm birth and to examine whether school-age spirometry patterns relate to subsequent lung-function trajectories. METHODS:Early-life analyses (n=511) examined predictors of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores at ages 6-8 years using multivariable regression. Spirometry-based phenotypes included prematurity-associated preserved-ratio impaired spirometry (pPRISm), prematurity-associated obstructive lung disease (POLD) and prematurity-associated dysanapsis. Longitudinal mixed-effects models assessed lung-function trajectories from ages 8 to 21 years. Parallel analyses were conducted in the National Health and Nutrition Examination Survey (NHANES). RESULTS:Lower weight-for-height at 4 years was non-linearly associated with both FEV1 and FVC at school age. Invasive ventilation in the first year of life was associated with lower FEV1 (β -0.62, 95% CI -0.96 to -0.28) and FVC (β -0.54, 95% CI -0.92 to -0.18). In exploratory analyses, pPRISm was inversely associated with neighbourhood income (risk ratio (RR) 0.63 per SD increase, 95% CI 0.46 to 0.88), and POLD was associated with invasive ventilation (RR 8.07, 95% CI 3.33 to 19.5). Similar subtypes and associations were observed in NHANES. School-age pPRISm was associated with progressive FEV1 z-score decline (age x pPRISm β -0.08 SD/year, 95% CI -0.15 to -0.02), while POLD was associated with improving FVC z-score (age x POLD β 0.13 SD/year, 95% CI 0.07 to 0.20). DISCUSSION:Early-childhood growth, neonatal respiratory exposures and school-age spirometry patterns help stratify long-term pulmonary risk among preterm-born children referred for pulmonary care.

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.

Bronchopulmonary dysplasia (BPD) is the second most common pediatric chronic respiratory disorder after asthma. Infants and children with BPD can have markedly different long-term respiratory outcomes despite being born at similar gestational ages, which is partially attributable to environmental exposures. Furthermore, these early life exposures can have lifelong consequences for the respiratory system, including decrements in lung function. In this review, we discuss what is known about the effects of environmental pollutants on respiratory outcomes for individuals born prematurely, and more specifically, those with BPD where data exist. Ultimately, targeting individuals with modifiable risk factors, such as preventable exposures, may improve long-term health outcomes for this vulnerable group.

Prosthetic joint infections (PJIs) following total joint arthroplasties are relatively rare but devastating complications. To date, no cases of Mycobacterium fortuitum PJIs associated with contaminated water supplies have been reported in the literature. Our report details 5 patients with Mycobacterium fortuitum PJIs related to a contaminated water supply at an ambulatory surgical center. These patients were identified by referral to our academic center. All underwent at least 1 revision surgery prior to referral and required prolonged broad-spectrum antibiotics. All had extensive wound complications, and 4 of 5 patients have received at least stage 1 of a 2-stage revision. All will require further surgery, but long-term outcomes remain relatively uncertain.

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.

Background: Bronchopulmonary dysplasia (BPD) is the most common long-term complication of prematurity. While 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. As such, we set out 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 Environmental Protection Agency data. Clinical data were obtained by chart review and caregiver questionnaires. Results: Non-white race, home ventilator usage, and lower median household income were associated with higher levels of air pollution exposure. After adjustment for these factors, moderate and high air pollution exposure were associated with requiring systemic steroids (OR 1.78 and 2.17 respectively) compared to low air pollution. Similarly, high air pollution exposure was associated with emergency department visits (OR 1.59). Conclusion: This study demonstrates an association between AAP exposure and BPD morbidity following 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.

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.

RATIONALE:In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma-associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. METHODS:This study included children with the diagnosis of BPD (n = 661) who were seen in outpatient pulmonary clinics at the Children's Hospital of Philadelphia between 2016 and 2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis, and acute care usage following initial hospital discharge. RESULTS:At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at the completion of initial pulmonary visit. Children started on an ICS as outpatients had a higher likelihood of ER visits (adjusted odds ratio: 2.68 ± 0.7), hospitalizations (4.81 ± 1.16), and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. CONCLUSIONS:This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

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

BACKGROUND:Bronchopulmonary dysplasia, a sequela of preterm birth, is the most common chronic respiratory disorder in infancy, and the second most common in children. Despite this, clinical care remains highly variable with guidelines supported by limited evidence, and do not provide specific guidance for timing of clinical follow-up, echocardiography, modalities of pulmonary function testing, etc. OBJECTIVE/METHODS: To further our understanding of care delivery for BPD, we sought to describe outpatient care patterns at tertiary care centers through survey data from 27 well-established BPD programs. RESULTS:We observed variability in referral patterns to outpatient BPD clinics, ancillary services provided, indications for follow-up echocardiograms, availability of lung function testing, and criteria for discharge from care. CONCLUSION:More comprehensive and detailed clinical guidelines similar to other pulmonary diseases such as asthma and cystic fibrosis should be developed to help standardize care and may improve long term outcomes.

Background: Fatigue can be a disabling multiple sclerosis (MS) symptom with no effective treatment options. Objective: Determine whether a low-fat diet improves fatigue in people with MS (PwMS). Methods: We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group. Subjects underwent 2 weeks of baseline diet data collection (24-hour diet recalls (24HDRs)), followed by randomization. The active group received 2 weeks of nutrition counseling and underwent a 12-week low-fat diet intervention. One set of three 24HDRs at baseline and week 16 were collected. We administered a food frequency questionnaire (FFQ) and Modified Fatigue Impact Scale (MFIS) every 4 weeks. The control group continued their pre-study diet and received diet training during the study completion. Results: We recruited 39 PwMS (20—active; 19—control). The active group decreased their daily caloric intake by 11% (95% confidence interval (CI): −18.5%, −3.0%) and the mean MFIS by 4.0 (95% CI: −12.0, 4.0) compared to the control (intent-to-treat). Sensitivity analysis strengthened the association with a mean MFIS difference of −13.9 (95% CI: −20.7, −7.2). Conclusions: We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in PwMS.

PDF - 240K, Overall segmentation results across the entire autosomal chromosomes in the genomic DNA titration series.

XLS - 100K, The list of SCAs detected by delta-theta in clinical specimens.

Childhood interstitial lung disease (chILD) is a heterogeneous group of diffuse lung diseases that can be challenging to diagnose. With relative rarity of individual entities, data are limited on disease prevalence, care patterns, and healthcare utilization. The objective of this study was to evaluate chILD prevalence and review diagnostic and clinical care patterns at our center. A single-center, retrospective cohort study was conducted of patients receiving care at the Children's Hospital of Philadelphia (CHOP) between 1 January 2019 and 31 December 2021. Through query of selected ICD-10 billing codes relevant for chILD and medical chart review, a total of 306 patients were identified receiving pulmonary care during this period. Respiratory symptom onset was documented to have developed before 2 years of age for 40% of cases. The most common diagnostic categories included those with oncologic disease (21.2%), bronchiolitis obliterans (10.1%), and connective tissue disease (9.5%). Genetic testing was performed in 49% of cases, while 36% underwent lung biopsy. Hospitalization at CHOP had occurred for 80.4% of patients, with 45.1% ever hospitalized in an intensive care unit. One-third of children had required chronic supplemental oxygen. Seven (2.3%) patients died during this 3-year period. Collectively, these data demonstrate the scope of chILD and extent of health care utilization at a large volume tertiary care center. This approach to cohort identification and EMR-driven data collection in chILD provides new opportunities for cohort analysis and will inform the feasibility of future studies.

PDF - 138K, The comparisons of representative delta-θ signals between 2 different methods of DNA isolation from brushing.

PDF - 79K, Legends for Supplementary Figures 1 through 5