A Randomized Trial of Inspiratory Training in Children and Adolescents With Obesity.

Introduction: Children with obesity suffer excess dyspnea that contributes to sedentariness. Developing innovative strategies to increase exercise tolerance and participation in children with obesity is a high priority. Because inspiratory training (IT) has reduced dyspnea, we sought to assess IT in children with obesity. Methods: We conducted a 6-week randomized IT trial involving 8- to 17-year-olds with obesity. Participants were randomized 1:1 to either high [75% of maximal inspiratory pressure (MIP)] or low resistance control (15% of MIP) three times weekly. Assessments included adherence, patient satisfaction, and changes in inspiratory strength and endurance, dyspnea scores and total activity level. Results: Among 27 randomized, 24 (89%) completed the intervention. Total session adherence was 72% which did not differ between treatment groups. IT was safe, and more than 90% felt IT benefitted breathing and general health. IT led to a mean improvement (95% CI) in inspiratory strength measured by MIP of 10.0 cm H2O (-3.5, 23.6; paired t-test, p = 0.139) and inspiratory endurance of 8.9 (1.0, 16.8; paired t-test, p = 0.028); however, there was no significant difference between high- and low-treatment groups. IT led to significant reductions in dyspnea with daily activity (p < 0.001) and in prospectively reported dyspnea during exercise (p = 0.024). Among the high- versus low-treatment group, we noted a trend for reduced dyspnea with daily activity (p = 0.071) and increased daily steps (865 vs. -51, p = 0.079). Discussion: IT is safe and feasible for children with obesity and holds promise for reducing dyspnea and improving healthy activity in children with obesity. Breathe-Fit trial NCT05412134.

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included. We evaluated the association between ICS prescription and clinical characteristics using univariable and multivariable logistic regression. RESULTS: Of 74,123 infants from 308 NICUs, 9253 (12.5%) were prescribed ICS: budesonide, fluticasone, or beclomethasone. Diagnosis of bronchopulmonary dysplasia (BPD), earlier gestational age, male sex, longer mechanical ventilation, oxygen support, and systemic steroids were independent risk factors for ICS prescription. CONCLUSIONS: Use of ICS is common in many NICUs and is associated with a diagnosis of BPD and healthcare utilization. Prospective trials are needed to establish the safety, efficacy, and optimal indication in this vulnerable population.

Association of Sputum Eosinophilia With Easily Measured Type-2 Inflammatory Biomarkers in Untreated Mild Persistent Asthma.

BACKGROUND: A multicenter clinical trial in patients with mild persistent asthma indicated that response to inhaled corticosteroids (ICS) is limited to those with sputum eosinophilia. However, testing for sputum eosinophilia is impractical in most clinical settings. OBJECTIVE: We examined associations between sputum eosinophilia and type 2 inflammatory biomarkers in untreated mild persistent asthma. METHODS: Induced sputum, blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and serum periostin were obtained twice during the 6-week run-in period in a clinical trial that enrolled patients 12 years and older with symptomatic, mild persistent asthma without controller therapy. The optimal threshold for each biomarker was based on achieving 80% or greater sensitivity. Performance of biomarkers (area under the receiver operating characteristics curve [AUC], range 0.0-1.0) in predicting sputum eosinophilia 2% or greater was determined; AUCs of 0.8 to 0.9 and more than 0.9 define excellent and outstanding discrimination, respectively. RESULTS: Of 564 participants, 27% were sputum eosinophilic, 83% were atopic, 70% had BEC of 200/uL or higher or FeNO of 25 ppb or greater; 64% of participants without sputum eosinophilia had elevated BEC or FeNO. The AUCs for BEC, FeNO, and both together in predicting sputum eosinophilia were all below the threshold for excellent discrimination (AUC 0.75, 0.78, and 0.79, respectively). Periostin (in adults) had poor discrimination (AUC 0.59; P = .02). CONCLUSIONS: In untreated mild persistent asthma, there is substantial discordance between sputum eosinophilia, BEC, and FeNO. Until prospective trials test the ability of alternative biomarkers to predict ICS response, BEC or FeNO phenotyping may be an option to consider ICS through a shared decision-making process with consideration of other clinical features.

The longitudinal association between asthma severity and physical fitness by neighborhood factors among New York City public school youth.

PURPOSE: This paper aims to examine the association between asthma severity and one-year lagged fitness in New York City Public school youth by neighborhood opportunity. METHODS: Using the Child Opportunity Index 2.0 and individual-level repeated measures NYC Office of School Health (OSH) fitness surveillance data (2010-2018), we ran multilevel mixed models stratified by neighborhood opportunity, adjusting for sex, race/ethnicity, grade level, poverty status, and time. Asthma severity was based on a physician-completed Asthma Medication Administration Form (MAF) from each school year and drawn from the Automated Student Health Record (ASHR). RESULTS: Across all youth in grades 4-12 (n = 939,598; 51.7 % male; 29.9 % non-Hispanic Black, 39.3 % Hispanic; 70.0 % high poverty), lower neighborhood opportunity was associated with lower subsequent fitness. Youth with severe asthma and very low and low neighborhood opportunity had the lowest 1-year lagged fitness z-scores - 0.24 (95 % CI, -0.34 to -0.14) and - 0.26 (95 % CI, -0.32 to -0.20), respectively, relative to youth with no asthma and very high opportunity. CONCLUSIONS: An inverse longitudinal relationship between asthma severity and subsequent fitness was observed. Study findings have implications for public health practitioners to promote physical activity and improved health equity for youth with asthma, taking neighborhood factors into account.

Supporting School Staff: Insights From Employee Health and Well-Being Programs.

BACKGROUND: The workplace is an important setting for health protection, health promotion, and disease prevention programs. In the school setting, employee health and well-being programs can address many physical and emotional concerns of school staff. This systematic review summarizes evidence-based approaches from employee health and well-being interventions supporting nutrition and physical activity (PA) in a variety of workplace settings. METHODS: The 2-phase systematic review included a search for articles within systematic reviews that met our criteria (addressing employee health and well-being programs; published 2010-2018; Phase 1) and the identification of individual articles from additional searches (addressing school-based employee interventions; published 2010-2020; Phase 2). We included 35 articles. FINDINGS: Across all studies and types of interventions and workplace settings, findings were mixed; however, multicomponent interventions appeared to improve health behaviors and health outcomes among employees. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Schools can apply this evidence from employee health and well-being programs in various workplace settings to implement coordinated and comprehensive employee health and well-being programs. CONCLUSIONS: Employee health and well-being programs may be effective at supporting nutrition and PA. Schools can use findings from employee health and well-being programs in workplaces other than schools to support school staff.

Pharmacokinetics of Oral Vitamin D in Children with Obesity and Asthma.

BACKGROUND AND OBJECTIVE: Vitamin D insufficiency is common in several pediatric diseases including obesity and asthma. Little data exist describing the pharmacokinetics of oral vitamin D in children or the optimal dosing to achieve therapeutic 25(OH)D targets. Describe the pharmacokinetics of oral Vitamin D in children with asthma. METHODS: This was a multi-center, randomized, open-label, oral supplementation study to describe the pharmacokinetics of vitamin D in children aged 6-17 years who have asthma and were overweight/obese. Participants had a serum 25(OH)D concentration between 10 and < 30 ng/mL at baseline. In Part 1 of the study, we assessed four 16-week dosing regimens for their ability to achieve 25(OH)D concentrations ≥ 40 ng/mL. Using serial serum 25(OH)D sampling over 28 weeks, we created a population pharmacokinetic model and performed dosing simulations to achieve 25(OH)D concentrations ≥ 40 ng/mL. In Part 2, the optimal regimen chosen from Part 1 was compared (2:1) to a standard-of-care control dose (600 international units [IU] daily) over 16 weeks. A final population pharmacokinetic model using both parts was developed to perform dosing simulations and determine important co-variates in the pharmacokinetics of vitamin D. RESULTS: Based on empiric and simulation data, the daily dose of 8000 IU and a loading dose of 50,000 IU were chosen; this regimen raised 25(OH)D concentrations above 40 ng/mL in the majority of participants while avoiding concentrations > 100 ng/mL. A 50,000-IU loading dose led to faster achievement of 25(OH)D therapeutic concentrations (≥ 40 ng/mL). The estimated median (5th-95th percentiles) apparent clearance of vitamin D from the final population pharmacokinetic model was 0.181 (0.155-0.206) L/h. The body mass index z-score was a significant covariate on apparent clearance and was associated with a significantly decreased median half-life in 25(OH)D (body mass index z-score 1.00-1.99: 97.7 days, body mass index z-score 2.00-2.99: 65.9 days, body mass index z-score ≥ 3.00: 39.1 days, p < 0.001). CONCLUSIONS: Obesity impacts vitamin D clearance and the half-life, but serum concentrations > 40 ng/mL can be reached in most children using a loading dose of 50,000 IU followed by a daily dose of 8000 IU. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT03686150.

Nationwide trends in hospitalization, medical costs, and mortality for asthma after introduction of biologics: A cross-sectional study in the United States.

BACKGROUND: Asthma is the most common inflammatory lung disease in the United States. Since 2015, biologic therapies have provided targeted treatment for patients with severe asthma. OBJECTIVE: To evaluate the trends for in-hospital outcomes of asthma before (2012-2014) and after (2016-2018) the introduction of biologic therapies for asthma. METHODS: We conducted a nationwide cross-sectional analysis of patients aged 2 years or older who were hospitalized for asthma between 2012 and 2018 using data from the Nationwide Readmissions Database. Outcomes included rates of asthma hospital admission and asthma-related 30-day readmission, hospital length of stay, hospital costs, and inpatient mortality. Generalized linear models assessed trends in rates of asthma admission and readmission, length of stay, costs, and mortality quarterly during 2012-2014 and 2016-2018. RESULTS: Among 691,537 asthma-related admissions, quarterly asthma admission rates significantly decreased (-0.90%, 95% CI = -1.46% to - 0.34%; P = 0.002) during 2016-2018, mainly among adults, but not during 2012-2014. Quarterly assessed readmission rates decreased by 2.40% (-2.85% to -1.96%; P < 0.0001) during 2012-2014 and by 2.12% (-2.74% to - 1.50%; P < 0.0001) during 2016-2018. Mean length of stay for asthma admissions decreased quarterly by 0.44% (-0.49% to - 0.38%; P < 0.0001) during 2012-2014 and by 0.27% (-0.34% to - 0.20%; P < 0.0001) during 2016-2018. Quarterly hospital costs for admissions were unchanged during 2012-2014 but increased by 0.28% (0.21% to 0.35%; P < 0.0001) during 2016-2018. There were no significant trends in inpatient mortality during 2012-2014 and 2016-2018. CONCLUSIONS: After the introduction of new biologics for severe asthma in 2015, asthma-related hospital admissions decreased significantly, whereas hospital costs increased. Asthma-related 30-day readmission rates and length of stay for asthma admissions continuously decreased, whereas inpatient mortality rates remained stable. DISCLOSURES: This work was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL136945. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The data that support the findings of this study are available from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project.

Asthma control in normal weight and overweight/obese asthmatic children following adenotonsillectomy.

OBJECTIVES: Childhood adenotonsillar hypertrophy (ATH) with sleep-disordered breathing (SDB) frequently occurs concomitant with asthma. Adenotonsillectomy and reduction in asthma severity association has been reported. We describe changes in asthma control in nonobese or normal weight and obese/overweight children undergoing adenotonsillectomy for SDB. METHODS: This prospective, nonrandomized cohort trial with 6-month follow-up at a tertiary children's hospital enrolled 41 children with persistent asthma undergoing adenotonsillectomy for SDB. Children with significant chronic medical conditions, premature birth (< 28 weeks), or recent respiratory infection were excluded. Patients were stratified by baseline BMI into nonobese or normal weight (BMI < 85 percentile) and obese/overweight (BMI > 85%). The primary outcome was change in Childhood Asthma Control Test (cACT) scores 3 and 6 months following adenotonsillectomy. Secondary outcome examined improvement in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) 3 and 6 months following adenotonsillectomy. RESULTS: Baseline characteristics were similar except for anthropometric measures and mean PACQLQ (P = .03). Children with nonobese or normal weight (n = 26) had statistically significant improvement in change in cACT at 3 (22.80 ± 2.33 vs. 17.86 ± 3.53, P < .001) and 6 (20.71±3.29 vs. 18.24 ± 4.16, P = .044) months compared with baseline. PACQLQ scores also improved at 3 (6.20 ± 0.87 vs. 4.56 ± 1.12, P < .001) and 6 (6.36 ± 0.72 vs. 4.93 ± 0.96, P < .001) months. Obese/overweight children (n = 10) had significant improvement in cACT scores at 6 months (20.00 ± 3.90 vs. 15.00 ± 6.90, P = .048). Change of cACT scores at 3 months (17.86 ± 3.53 vs. 14.86 ± 6.31, P = .272) was not significantly different. PACQLQ scores improved at 3 (5.47 ± 1.09 vs. 3.70 ± 0.85, P < .001) and 6 (5.75 ± 2.19 vs. 3.67 ± 1.04, P = .016) months. CONCLUSION: Nonobese or normal-weight children undergoing adenotonsillectomy demonstrated significant improvement in asthma control scores at 3 and 6 and obese/overweight children at 6 months. Using the PACQLQ, caregiver quality of life improved for all children at 3 and 6 months. Surgical management of ATH in children with comorbid SBD and asthma is a good treatment option.

Subgroup Analysis of a Randomized Trial of the Effects of Positive Messaging on Patient-Reported Outcomes with Asthma - Effect of Obesity.

Objective: Asthma in obese patients represents a specific phenotype that is associated with increased symptoms, more frequent and severe exacerbations, reduced responsiveness to treatment, and decreased quality of life. Marketing and placebos have been shown to alter subjective responses to interventions in both asthma and obesity. We evaluated obesity as a potential treatment effect modifier of the effects enhanced drug messaging or placebos on subjective asthma outcomes. Methods: We conducted a secondary analysis of a multicenter, randomized clinical trial that studied the effect of messaging and placebos on asthma outcomes. A total of 601 participants were randomized (1:1:1:1:1) to one of 5 groups: enhanced messaging with montelukast or placebo, neutral messaging with montelukast or placebo, or usual care and followed for 4 weeks after randomization. We compared baseline characteristics by obesity status for 600 participants with data on body weight. Obesity was evaluated as an effect modifier for enhanced messaging (versus neutral messaging) and on placebo effects (versus usual care) in 362 participants assigned to a placebo group or usual care for three asthma questionnaires: Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Asthma Symptoms Utility Index. Results: Overall, 227 (37%) of participants were obese. Obese participants were older (mean age 41 vs 34), more likely female (82% vs 67%) and self-identified as Black (44% vs 25%) than non-obese participants. As previously published, enhanced messaging was associated with improvements in patient-reported asthma scores, but there was no evidence for a placebo effect. Obesity status did not influence the message effects nor did it modify responses to placebo. Conclusion: Obesity has been shown to be an important factor associated with asthma outcomes and an effect modifier of drug treatment effects. We conducted a post hoc, subgroup analysis of data from a multicenter randomized trial of enhanced messaging and placebo associated with drug treatment on asthma outcomes. Our findings suggest that observed differences in treatment effects between obese and non-obese patients sometimes seen in trials of asthma treatments are unlikely to be due to different "placebo" effects of treatment and may reflect differential physiologic effects of active agents.

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.

Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmonary hypertension. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus is a promising candidate for BPD. Following phase I studies, we developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD. SIL02 is a randomized, double-blind, placebo-controlled, 3-cohort, sequential dose-escalating trial of enteral or intravenous (IV) sildenafil dosed every 8 h for up to 34 days. The target IV doses were 0.125, 0.5 and 1 mg/kg/dose in cohorts 1, 2 and 3, respectively; while the enteral doses will be double the IV doses. Eligible infants must be < 29 weeks' gestation at birth and requiring respiratory support at 7-28 days' postnatal age. Adverse events and preliminary effectiveness will be compared by treatment group. Using the final population PK model, empirical Bayesian estimates will be generated for each patient. Preliminary effectiveness will be measured by the incidence of moderate to severe BPD or death at 36 weeks and change in the BPD risk estimation.

Inspiratory Muscle Rehabilitation Training in Pediatrics: What Is the Evidence?

Pulmonary rehabilitation is typically used for reducing respiratory symptoms and improving fitness and quality of life for patients with chronic lung disease. However, it is rarely prescribed and may be underused in pediatric conditions. Pulmonary rehabilitation can include inspiratory muscle training that improves the strength and endurance of the respiratory muscles. The purpose of this narrative review is to summarize the current literature related to inspiratory muscle rehabilitation training (IMRT) in healthy and diseased pediatric populations. This review highlights the different methods of IMRT and their effects on respiratory musculature in children. Available literature demonstrates that IMRT can improve respiratory muscle strength and endurance, perceived dyspnea and exertion, maximum voluntary ventilation, and exercise performance in the pediatric population. These mechanistic changes help explain improvements in symptomology and clinical outcomes with IMRT and highlight our evolving understanding of the role of IMRT in pediatric patients. There remains considerable heterogeneity in the literature related to the type of training utilized, training protocols, duration of the training, use of control versus placebo, and reported outcome measures. There is a need to test and refine different IMRT protocols, conduct larger randomized controlled trials, and include patient-centered clinical outcomes to help improve the evidence base and support the use of IMRT in patient care.

The CDC Worksite Health ScoreCard: A Tool to Advance Workplace Health Promotion Programs and Practices.

INTRODUCTION: The CDC Worksite Health ScoreCard (ScoreCard) is a free, publicly available survey tool designed to help employers assess the extent to which they have implemented evidence-based interventions or strategies at their worksites to improve the health and well-being of employees. We examined how, how broadly, and to what effect the ScoreCard has been applied. METHODS: We analyzed peer-reviewed and grey literature along with the ScoreCard database of online submissions from January 2012 through January 2021. Our inclusion criteria were workplace settings, adult working populations, and explicit use of the ScoreCard. RESULTS: We found that the ScoreCard had been used in 1) surveillance efforts by states, 2) health promotion training and technical assistance, 3) research on workplace health promotion program effectiveness, and 4) employer efforts to improve program design, implementation, and evaluation. CONCLUSION: The ScoreCard has been used as intended to support the development, planning, monitoring, and continuous improvement of workplace health promotion programs. Our review revealed gaps in the tool and opportunities to improve it by 1) enhancing surveillance efforts, 2) engaging employers in low-wage industries, 3) adding new questions or topic areas, and 4) conducting quantitative studies on the relationship between improvements in the ScoreCard and employee health and well-being outcomes.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

Environmental and clinical data utility in pediatric asthma exacerbation risk prediction models.

BACKGROUND: Asthma exacerbations are triggered by a variety of clinical and environmental factors, but their relative impacts on exacerbation risk are unclear. There is a critical need to develop methods to identify children at high-risk for future exacerbation to allow targeted prevention measures. We sought to evaluate the utility of models using spatiotemporally resolved climatic data and individual electronic health records (EHR) in predicting pediatric asthma exacerbations. METHODS: We extracted retrospective EHR data for 5982 children with asthma who had an encounter within the Duke University Health System between January 1, 2014 and December 31, 2019. EHR data were linked to spatially resolved environmental data, and temporally resolved climate, pollution, allergen, and influenza case data. We used xgBoost to build predictive models of asthma exacerbation over 30-180 day time horizons, and evaluated the contributions of different data types to model performance. RESULTS: Models using readily available EHR data performed moderately well, as measured by the area under the receiver operating characteristic curve (AUC 0.730-0.742) over all three time horizons. Inclusion of spatial and temporal data did not significantly improve model performance. Generating a decision rule with a sensitivity of 70% produced a positive predictive value of 13.8% for 180 day outcomes but only 2.9% for 30 day outcomes. CONCLUSIONS: EHR data-based models perform moderately wellover a 30-180 day time horizon to identify children who would benefit from asthma exacerbation prevention measures. Due to the low rate of exacerbations, longer-term models are likely to be most clinically useful. TRIAL REGISTRATION: Not applicable.

Asthma and the Risk of SARS-CoV-2 Infection Among Children and Adolescents.

OBJECTIVES: Over 6 million pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred in the United States, but risk factors for infection remain poorly defined. We sought to evaluate the association between asthma and SARS-CoV-2 infection risk among children. METHODS: We conducted a retrospective cohort study of children 5 to 17 years of age receiving care through the Duke University Health System and who had a Durham County, North Carolina residential address. Children were classified as having asthma using previously validated electronic health record-based definitions. SARS-CoV-2 infections were identified based on positive polymerase chain reaction testing of respiratory samples collected between March 1, 2020, and September 30, 2021. We matched children with asthma 1:1 to children without asthma, using propensity scores and used Poisson regression to evaluate the association between asthma and SARS-CoV-2 infection risk. RESULTS: Of 46 900 children, 6324 (13.5%) met criteria for asthma. Children with asthma were more likely to be tested for SARS-CoV-2 infection than children without asthma (33.0% vs 20.9%, P < .0001). In a propensity score-matched cohort of 12 648 children, 706 (5.6%) children tested positive for SARS-CoV-2 infection, including 350 (2.8%) children with asthma and 356 (2.8%) children without asthma (risk ratio: 0.98, 95% confidence interval: 0.85-1.13. There was no evidence of effect modification of this association by inhaled corticosteroid prescription, history of severe exacerbation, or comorbid atopic diseases. Only 1 child with asthma required hospitalization for SARS-CoV-2 infection. CONCLUSIONS: After controlling for factors associated with SARS-CoV-2 testing, we found that children with asthma have a similar SARS-CoV-2 infection risk as children without asthma.

Association between postmenstrual age and furosemide dosing practices in very preterm infants.

OBJECTIVE: Furosemide renal clearance is slow after very preterm (VP) birth and increases with postnatal maturation. We compared furosemide dose frequency and total daily dose between postmenstrual age (PMA) groups in VP infants. STUDY DESIGN: Observational cohort study of VP infants exposed to a repeated-dose course of furosemide in Pediatrix neonatal intensive care units (NICU) from 1997 to 2016. RESULTS: We identified 6565 furosemide courses among 4638 infants. There were no statistically significant differences between PMA groups on the odds of receiving more frequent furosemide dosing. Furosemide courses initiated at <28 weeks PMA were associated with a higher total daily dose than those initiated at a later PMA. CONCLUSIONS: Furosemide dosing practices in the NICU are similar across PMA groups, despite maturational changes in drug disposition. Research is needed to identify and test rational dosing strategies across the PMA spectrum for this commonly used but unproven pharmacotherapy.

Biomarkers to Predict Response to Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists in Adolescents and Adults with Mild Persistent Asthma.

Rationale: Whether biomarkers can be used to predict response to inhaled corticosteroids (ICS) or long-acting muscarinic antagonists (LAMA) in mild persistent asthma is unclear. Objectives: In a prespecified exploratory analysis of a randomized clinical trial of 295 participants 12 years of age or older with uncontrolled mild persistent asthma, we sought to identify biomarkers of treatment response after 12 weeks of ICS (mometasone, 200 µg or 220 µg twice/d), LAMA (tiotropium, 5 µg/d), or placebo in adults (⩾18 yr) and adolescents (12-17 yr) separately. Methods: The primary outcome was a composite outcome of asthma control (treatment failure, asthma control days, and forced expiratory volume in 1 second [FEV1]). Analyses examined type 2 inflammatory biomarkers and physiologic biomarkers. We assessed the area under the receiver operating characteristic curve (AUC) for response to ICS and LAMA (each versus placebo). An AUC of 0.5 suggests no discrimination, 0.7-0.8 is considered acceptable, more than 0.8-0.9 is considered excellent, and more than 0.9 is considered outstanding. Results: In 237 adults, sputum and blood eosinophil levels and fractional exhaled nitric oxide (FeNO) each predicted ICS response (AUCs: 0.61 [95% confidence interval (CI), 0.53-0.69], 0.64 [95% CI, 0.56-0.72], and 0.62 [95% CI, 0.54-0.70], respectively; all P < 0.01); the AUC for blood eosinophil levels and FeNO together was 0.66 (95% CI, 0.58-0.74; P < 0.001). In 58 adolescents, the number of positive aeroallergens and total serum immunoglobulin E each predicted ICS response (AUCs: 0.69 [95% CI, 0.52-0.85] and 0.73 [95% CI, 0.58-0.87], respectively; both P < 0.03); the AUC for both together was 0.73 (95% CI, 0.58-0.87; P = 0.003). After ipratropium bromide, FEV1 reversibility predicted LAMA response in adults (AUC: 0.61 [95% CI, 0.53-0.69], P = 0.007) but not in adolescents. Conclusions: The AUCs of the type 2 inflammatory biomarkers and physiological biomarkers we examined may not be high enough to confidently identify individuals with asthma who respond to ICS and LAMA. However, our findings indicate that the biomarkers that predict response to ICS or LAMA may differ in adults versus adolescents with uncontrolled mild persistent asthma. Prospective, biomarker-stratified clinical trials are needed to confirm these findings and to identify first-line controllers tailored for each population.

Reduced pediatric urgent asthma utilization and exacerbations during the COVID-19 pandemic.

The COVID-19 pandemic has had a profound impact on healthcare access and utilization, which could have important implications for children with chronic diseases, including asthma. We sought to evaluate changes in healthcare utilization and outcomes in children with asthma during the COVID-19 pandemic. We used electronic health records data to evaluate healthcare use and asthma outcomes in 3959 children and adolescents, 5-17 years of age, with a prior diagnosis of asthma who had a history of well-child visits and encounters within the healthcare system. We assessed all-cause healthcare encounters and asthma exacerbations in the 12-months preceding the start of the COVID-19 pandemic (March 1, 2019-February 29, 2020) and the first 12 months of the pandemic (March 1, 2020-February 28, 2021). All-cause healthcare encounters decreased significantly during the pandemic compared to the preceding year, including well-child visits (48.1% during the pandemic vs. 66.6% in the prior year; p < .01), emergency department visits (9.7% vs. 21.0%; p < .01), and inpatient admissions (1.6% vs. 2.5%; p < .01), though there was over a 100-fold increase in telehealth encounters. Asthma exacerbations that required treatment with systemic steroids also decreased (127 vs. 504 exacerbations; p < .01). Race/ethnicity was not associated with changes in healthcare utilization or asthma outcomes. The COVID-19 pandemic corresponded to dramatic shifts in healthcare utilization, including increased telehealth use and improved outcomes among children with asthma. Social distancing measures may have also reduced asthma trigger exposure.