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 recruited from the multicenter Bronchopulmonary Dysplasia (BPD) Collaborative. STUDY DESIGN: A cross-sectional study was performed among participants less than 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 1,011 subjects born at a mean gestational age of 26.4 ± 2.2 weeks were included. Most (66.6%) had severe BPD. Over 40% of subjects were exposed to at least one source of indoor air pollution. The odds of reporting an emergency department visit (OR 1.7 [1.18, 2.45], antibiotic use (OR 1.9 [1.12, 3.21]), or a systemic steroid course (OR 2.18 [1.24, 3.84]) were significantly higher in subjects reporting exposure to secondhand smoke (SHS) compared with those without SHS exposure. Subjects reporting exposure to air pollution (not including SHS) also had a significantly greater odds (OR 1.48 [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. CONCLUSION: Exposure to indoor air pollution, especially SHS, was associated with acute respiratory morbidities, including ED visits, antibiotics for respiratory illnesses, and systemic steroid use.

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.

Transpyloric feeding is associated with adverse in-hospital outcomes in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the association of transpyloric feeding (TPF) with the composite outcome of tracheostomy or death for patients with severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: Retrospective multi-center cohort study of preterm infants <32 weeks with sBPD receiving enteral feedings. We compared infants who received TPF at 36, 44, or 50 weeks post-menstrual age to those who did not receive TPF at any of those timepoints. Odds ratios were adjusted for gestational age, small for gestational age, male sex, and invasive ventilation and FiO2 at 36 weeks. RESULTS: Among 1039 patients, 129 (12%) received TPF. TPF was associated with an increased odds of tracheostomy or death (aOR 3.5, 95% CI 2.0-6.1) and prolonged length of stay or death (aOR 3.1, 95% CI 1.9-5.2). CONCLUSIONS: Use of TPF in sBPD after 36 weeks was infrequent and associated with worse in-hospital outcomes, even after adjusting for respiratory severity at 36 weeks.

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.

Comparison of Pneumotachometer and Portable Digital Turbine Spirometry for Field-Based Assessment: An Air Quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia Study.

Introduction: Data on the use of remote spirometry are limited in the pediatric population. We sought to assess the feasibility and accuracy of a digital turbine spirometer, Medical International Research (MIR) Spirobank Smart (MIR, New Berlin, WI, USA), compared with a pneumotachography spirometer, Pneumotrac (Vitalograph Inc., Lenexa, KS, USA), in field-based clinical research. Methods: This is a cross-sectional study of a subgroup of school-aged participants enrolled in the Air quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia (BPD) study, who performed same-day paired coached baseline spirometry measurements from the Pneumotrac and MIR devices. Proportion of successful tests was estimated for each device and compared using McNemar's test. Correlation between devices forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) was analyzed by Lin's concordance correlation, and Bland-Altman plots were generated. Results: Twenty-one participants with history of BPD completed home spirometry maneuvers on both devices. The mean age of participants was 8.7 years. The mean FEV1 and FVC measurement was 81% predicted and 90.4% predicted, respectively. The proportion of acceptable tests appeared higher using Pneumotrac (81%) than when using MIR (67%), although without evidence of discordance (P = 0.317). Among subjects with successful tests on both devices, Lin's concordance correlation demonstrated moderate agreement (FEV1 r = 0.955, 95% confidence interval [CI]: 0.87-0.98; FVC r = 0.971, CI: 0.91-0.99). The mean difference in FEV1 between Pneumotrac and MIR was 0.079 L (95% limits of agreement were -0.141 to 0.298 L) and FVC was 0.075 L (95% limits of agreement were -0.171 to 0.322 L). These were relatively small and without evidence of systematic or volume-dependent bias. Conclusions: Utilizing turbine spirometers may be a promising and feasible way to perform pulmonary function testing for field research in children.

Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features. OBJECTIVE: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRSAsthma) and spirometry (FEV1 and FEV1/forced vital capacity; PRSspiro) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO). METHODS: We developed and tested 2 asthma PRSs and applied the higher performing PRSAsthma and a previously published PRSspiro to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record-based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies. We assessed the association of PRSs with COPD and asthma using modified random-effects and binary-effects meta-analyses, and ACO and asthma exacerbations in specific cohorts. Models were adjusted for confounders and genetic ancestry. RESULTS: In meta-analyses of 102,477 participants, the PRSAsthma (odds ratio [OR] per SD, 1.16 [95% CI, 1.14-1.19]) and PRSspiro (OR per SD, 1.19 [95% CI, 1.17-1.22]) both predicted asthma, whereas the PRSspiro predicted COPD (OR per SD, 1.25 [95% CI, 1.21-1.30]). However, results differed by cohort. The PRSspiro was not associated with COPD in GERA and Mass General Brigham Biobank. In the Genetic Epidemiology of COPD study, the PRSAsthma (OR per SD: Whites, 1.3; African Americans, 1.2) and PRSspiro (OR per SD: Whites, 2.2; African Americans, 1.6) were both associated with ACO. In GERA, the PRSAsthma was associated with asthma exacerbations (OR, 1.18) in Whites; the PRSspiro was associated with asthma exacerbations in White, LatinX, and East Asian participants. CONCLUSIONS: PRSs for asthma and spirometry are both associated with ACO and asthma exacerbations. Genetic prediction performance differs in research versus electronic health record-based cohorts.

Obstructive sleep apnea is associated with use of assisted ventilation among children with bronchopulmonary dysplasia hospitalized with respiratory illness: A nationwide inpatient cohort.

OBJECTIVE (S): Children with bronchopulmonary dysplasia (BPD) are at higher risk of respiratory insufficiency during respiratory illness. We aimed to investigate whether obstructive sleep apnea (OSA) is associated with increased morbidity among children with BPD hospitalized with acute respiratory illnesses. STUDY DESIGN: Hospital discharge records were obtained from the Kid's Inpatient Database for children <21 years of age with BPD hospitalized for acute respiratory illness between 1997 and 2012. Acute respiratory illnesses included bacterial and/or viral pneumonia, bronchiolitis, acute upper respiratory tract infections, aspiration pneumonia, or asthma exacerbation. The primary exposure was OSA. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were noninvasive mechanical ventilation (NIMV), length of hospital stay (LOS), and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for BPD-associated comorbidities. RESULTS: Among 33,640 hospitalizations of children with BPD for acute respiratory illness, there were 607 (1.8%) cases with comorbid OSA vs. 33,033 (98.2%) controls without OSA. Patients with OSA were more likely to have aspiration pneumonia, central sleep apnea, obesity, laryngeal stenosis, congenital airway, and skull/face/jaw anomalies. Multivariable regression showed that OSA was associated with IMV (OR 1.45, 95% CI 1.09-1.94, p = 0.012) and NIMV (OR 2.61, 95% CI 1.71-3.98, p < 0.001), but not LOS or IACH. CONCLUSIONS: In BPD patients hospitalized with acute respiratory illness, having OSA is associated with increased risks for respiratory insufficiency requiring noninvasive or invasive mechanical ventilation. Clinicians should consider OSA, along with other BPD-associated comorbidities, in the management of this population.

Pre-Flight Hypoxemia Challenge Testing in Bronchopulmonary Dysplasia.

BACKGROUND AND OBJECTIVES: Former premature infants with bronchopulmonary dysplasia (BPD) are at risk for hypoxemia during air travel, but it is unclear until what age. We aimed to determine pass rates for high altitude simulation testing (HAST) by age in children with BPD and identify risks for failure. METHODS: Retrospective, observational analysis of HAST in children with BPD at Boston Children's Hospital, using interval censoring to estimate the time-to-event curve of first pass. Curves were stratified by neonatal risk factors. Pass was considered lowest Spo2 ≥ 90%, or ≥94% for subjects with ongoing pulmonary hypertension (PH). RESULTS: Ninety four HAST studies were analyzed from 63 BPD subjects; 59 studies (63%) were passed. At 3 months corrected gestational age (CGA), 50% of subjects had passed; at 6 months CGA, 67% has passed; at 12 and 18 months CGA, 72% had passed; and at 24 months CGA, 85% had passed. Neonatal factors associated with delayed time-to-pass included postnatal corticosteroid use, respiratory support at NICU discharge, and tracheostomy. BPD infants who did not require respiratory support at 36 weeks were likely to pass (91%) at 6 months CGA. At 24 months, children least likely to pass included those with a history of PH (63%) and those discharged from the NICU with oxygen or respiratory support (71%). CONCLUSIONS: Children with BPD on respiratory support at 36 weeks should be considered for preflight hypoxemia challenges through at least 24 months CGA, and longer if they had PH or went home from NICU on respiratory support.

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.

X chromosome associations with chronic obstructive pulmonary disease and related phenotypes: an X chromosome-wide association study.

BACKGROUND: The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations. METHODS: Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case-control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses. RESULTS: Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV1/FVC ([Formula: see text] 0.020, SE 0.004, p 4.97 × 10-08), with suggestive evidence of association with FEV1 ([Formula: see text] 0.092, SE 0.018, p 3.40 × 10-07). Sex-stratified analyses revealed X chromosome variants that were differentially trending in one sex, with significantly different effect sizes or directions. CONCLUSIONS: This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.

Discharge Practices for Infants with Bronchopulmonary Dysplasia: A Survey of National Experts.

OBJECTIVE: To establish consensus practices among a panel of national experts for the discharge of premature infants with bronchopulmonary dysplasia (BPD) from the hospital to home. STUDY DESIGN: We conducted a Delphi study that included US neonatologists and pediatric pulmonologists from the Bronchopulmonary Dysplasia Collaborative to establish consensus practices-defined as recommendations with at least 80% agreement-for infants with BPD being discharged from the hospital. Specifically, we evaluated recommendations for diagnostic tests to be completed around discharge, follow-up respiratory care, and family education. RESULTS: Thirty-one expert participants completed 3 rounds of surveys, with a 99% response rate (92 of 93). Consensus was established that infants with moderate-severe BPD (ie, those who remain on respiratory support at 36 weeks) and those discharged on oxygen should be targeted for in-person pulmonary follow-up within 1 month of hospital discharge. Specialized neonatal follow-up is an alternative for infants with mild BPD. Infants with moderate or severe BPD should have an echocardiogram performed after 36 weeks to screen for pulmonary hypertension. Infants with BPD warrant additional evaluations if they have growth restriction or poor growth, pulmonary hypertension, or tachypnea and if they are discharged to home on oxygen, diuretics, or nonoral feeds. CONCLUSIONS: This Delphi survey establishes expert consensus around best practices for follow-up respiratory management and routine evaluation for infants with BPD surrounding neonatal discharge. Areas of disagreement for which consensus was not established are discussed.

Approaches to Interdisciplinary Care for Infants with Severe Bronchopulmonary Dysplasia: A Survey of the Bronchopulmonary Dysplasia Collaborative.

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: · Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. · Benefits of interdisciplinary care for children have been observed in other chronic conditions.. · Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..

Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater health care use for respiratory illnesses during the first 3 years of life. STUDY DESIGN: Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from 9 BPD specialty clinics in the US. All subjects were former infants born preterm (<34 weeks) with BPD (71% severe) requiring outpatient follow-up between 0 and 3 years of age. Mixed logistic regression models were used to test for associations. RESULTS: Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to 3 years of age also were more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6 and 12 months of chronological age. CONCLUSIONS: In this study, children born preterm with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids, and have chronic respiratory symptoms compared with children not in daycare, indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.

Cost Savings Without Increased Risk of Respiratory Hospitalization for Preterm Children after the 2014 Palivizumab Policy Update.

OBJECTIVE: Our objective was to compare rates of hospitalizations for respiratory illnesses in preterm and full-term (FT) children for 4 years before and after the 2014 update to the American Academy of Pediatrics (AAP) respiratory syncytial virus (RSV) immunoprophylaxis guidance, which restricted eligibility among infants born at 29 to 34 weeks in the first winter and all preterm infants in the second winter after neonatal discharge. STUDY DESIGN: We conducted pre-post and interrupted time series analyses on claims data from a commercial national managed care plan. We compared the number of RSV and all respiratory hospital admissions in the first and second RSV seasons after neonatal discharge among a cohort of preterm children, regardless of palivizumab status, in the 4 years before and after the implementation of the 2014 palivizumab eligibility change. A FT group was included for reference. RESULTS: The cohort included 821 early preterm (EP, <29 weeks), 4,790 moderate preterm (MP, 29-34 weeks), and 130,782 FT children. Palivizumab use after the policy update decreased among MP children in the first and second RSV seasons after neonatal discharge, without any change in the odds of hospitalization with RSV or respiratory illness. For the EP group, there was no change in the rate of palivizumab or the odds of hospitalization with RSV or respiratory illness after the policy update. For the FT group, there was a slight decrease in odds of hospitalization post-2014 after the policy update. The interrupted time series did not reveal any secular trends over time in hospitalization rates among preterm children. Following the policy change, there were cost savings for MP children in the first and second RSV seasons, when accounting for the cost of hospitalizations and the cost of palivizumab. CONCLUSION: Hospitalizations for RSV or respiratory illness did not increase, and cost savings were obtained after the implementation of the 2014 AAP palivizumab prophylaxis policy. KEY POINTS: · Palivizumab use decreased among children born moderate preterm (29 to34 weeks) after the 2014 palivizuamb policy update.. · There was no change in odds of hospitalization with respiratory syncitial virus or respiratory illness among preterm infants after the policy update when compared to before.. · There were cost savings, when accounting for the cost of hospitalizations and the cost of palivizumab, after the policy update among children born moderate preterm..

Insurance coverage and respiratory morbidities in bronchopulmonary dysplasia.

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge. METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart review. Surveys for clinical outcomes were administered to caregivers. RESULTS: Of the 470 subjects included in this study, 249 (53.0%) received employer-based insurance coverage and 221 (47.0%) received Medicaid as sole coverage at least once between 0 and 3 years of age. The Medicaid group was twice as likely to have sick visits (adjusted odd ratio [OR]: 2.06; p = 0.009) and emergency department visits (aOR: 2.09; p = 0.028), and three times more likely to be admitted for respiratory reasons (aOR: 3.04; p = 0.001) than those in the employer-based group. Additionally, those in the Medicaid group were more likely to have nighttime respiratory symptoms (aOR: 2.62; p = 0.004). CONCLUSIONS: Children with BPD who received Medicaid coverage were more likely to utilize acute care and have nighttime respiratory symptoms during the first 3 years of life. More comprehensive studies are needed to determine whether the use of Medicaid represents a barrier to accessing care, lower socioeconomic status, and/or a proxy for detrimental environmental exposures.

Genetic Associations and Architecture of Asthma-COPD Overlap.

BACKGROUND: Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. RESEARCH QUESTION: What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? STUDY DESIGN AND METHODS: We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10-6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). RESULTS: We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10-8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. INTERPRETATION: We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.

Long-term respiratory and developmental outcomes in children with bronchopulmonary dysplasia and history of tracheostomy.

OBJECTIVE: The long-term morbidity among children with severe bronchopulmonary dysplasia who require tracheostomy (tBPD) relative to those without tracheostomy (sBPD) is not well characterized. We compared childhood lung function and neurodevelopmental outcomes in tBPD and sBPD. STUDY DESIGN: Retrospective case-control study of N = 49 tBPD and N = 280 sBPD subjects in Boston Children's Hospital Preterm Lung Patient Registry and medical record. We compared NICU course, childhood spirometry, and neurodevelopmental testing. RESULT: tBPD subjects were more likely than sBPD to be Black, have pulmonary hypertension, and have subglottic stenosis. tBPD subjects had lower maximal childhood FEV1 % predicted (ß = -0.14) and FEV1/FVC (ß = -0.08); spirometry curves were more likely to suggest fixed extrathoracic obstruction. tBPD subjects had greater cognitive and motor delays <24 months, and greater cognitive delays >24 months. CONCLUSION: Compared to subjects with sBPD who did not require tracheostomy, tBPD subjects suffer from increased long-term impairment in respiratory function and neurodevelopment.

Air quality, Environment and Respiratory Outcomes in Bronchopulmonary Dysplasia, the AERO-BPD cohort study: design and adaptation during the SARS-CoV-2 pandemic.

INTRODUCTION: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER: NCT04107701.

Lung function trajectories in children with post-prematurity respiratory disease: identifying risk factors for abnormal growth.

BACKGROUND: Survivors of prematurity are at risk for abnormal childhood lung function. Few studies have addressed trajectories of lung function and risk factors for abnormal growth in childhood. This study aims to describe changes in lung function in a contemporary cohort of children born preterm followed longitudinally in pulmonary clinic for post-prematurity respiratory disease and to assess maternal and neonatal risk factors associated with decreased lung function trajectories. METHODS: Observational cohort of 164 children born preterm ≤ 32 weeks gestation followed in pulmonary clinic at Boston Children's Hospital with pulmonary function testing. We collected demographics and neonatal history. We used multivariable linear regression to identify the impact of neonatal and maternal risk factors on lung function trajectories in childhood. RESULTS: We identified 264 studies from 82 subjects with acceptable longitudinal FEV1 data and 138 studies from 47 subjects with acceptable longitudinal FVC and FEV1/FVC data. FEV1% predicted and FEV1/FVC were reduced compared to childhood norms. Growth in FVC outpaced FEV1, resulting in an FEV1/FVC that declined over time. In multivariable analyses, longer duration of mechanical ventilation was associated with a lower rate of rise in FEV1% predicted and greater decline in FEV1/FVC, and postnatal steroid exposure in the NICU was associated with a lower rate of rise in FEV1 and FVC % predicted. Maternal atopy and asthma were associated with a lower rate of rise in FEV1% predicted. CONCLUSIONS: Children with post-prematurity respiratory disease demonstrate worsening obstruction in lung function throughout childhood. Neonatal risk factors including exposure to mechanical ventilation and postnatal steroids, as well as maternal atopy and asthma, were associated with diminished rate of rise in lung function. These results may have implications for lung function trajectories into adulthood.