To identify clinical characteristics that may be associated with persistence or progression of mild sleep-disordered breathing (SDB) in children who are observed without surgery. This is a secondary analysis of the control arm of the Pediatric Adenotonsillectomy Trial for Snoring (PATS), which randomized 458 children aged 3.0 to 12.9 years with mild SDB (snoring with obstructive apnea–hypopnea index [oAHI] < 3 events/hour) to early adenotonsillectomy (eAT) versus watchful waiting with supportive care (WWSC). Participants were assessed at baseline and 12 months with the Pediatric Sleep Questionnaire–Sleep-Related Breathing Disorder (PSQ-SRBD) scale and polysomnography (PSG). We tested for factors predictive of either (1) PSG progression defined by a 12-month oAHI ≥ 3 or (2) symptom persistence or progression defined by a 12-month PSQ-SRBD score ≥ 0.33. A total of 234 participants were observed (mean age 6.2 years, 111 [47

BACKGROUND:Asthma is characterized by airway inflammation and bronchoconstriction. Recent therapies have addressed inflammation but not bronchoconstriction. S-Nitrosoglutathione (GSNO) is an endogenous smooth muscle relaxant that also affects β2-adrenergic response. Airway GSNO levels are often low in asthma. OBJECTIVE:We studied the effects of inhaled GSNO (iGSNO) in human asthma. METHODS:We measured the effects and metabolism of iGSNO, with a focus on forced expiratory volume in 1 second, β2-adrenergic agonist response and fractional exhaled nitric oxide, and expression of GSNO metabolic genes from bronchoscopic biopsy samples using spatial transcriptomics. RESULTS:iGSNO increased forced expiratory volume in 1 second and β2-adrenergic receptor response; the magnitude of increase was related, and additive, to the receptor response (P < .001). SCoR2 (AKR1A1 gene), encoding a GSNO degrading enzyme, was upregulated in airway epithelium, and higher SCoR2 expression was associated with reduced iGSNO bronchodilation. Sustained elevation in fractional exhaled nitric oxide after iGSNO, indicating reduced GSNO catabolism, was a biomarker for iGSNO effect. CONCLUSION:iGSNO could represent personalized asthma therapy, augmenting β2-adrenergic receptor agonist benefit.

Introduction: Moderate to severe obstructive sleep-disordered breathing (oSDB) in children has been associated with elevated blood pressure (BP) and hypertension (HTN). While adenotonsillectomy has been shown to benefit children with elevated BP, its impact in children with only mild oSDB, remains unclear. Study Design and Methods: We conducted a secondary outcome analysis of the Pediatric Adenotonsillectomy Trial for Snoring, a randomized clinical trial that enrolled 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (oAHI) < 3/hour. Children were randomized to early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC) and followed for 12 months. Systolic BP (SBP) and diastolic BP (DBP) measurements were collected at baseline, 6 months, and 12 months during daytime research visits. We hypothesized that 12-month BP trajectories would differ between study arms. The treatment effect on BP changes was evaluated using mixed-effects models. A P < 0.05 was considered significant. Results: Of the 458 participants analyzed, 230 (50.2%) were female, 122 (26.6%) Black, and 169 (36.9%) had overweight/obesity (BMI > 85th percentile). A total of 394 (86%) children completed the 12-month follow-up and 231 (50.3%) underwent eAT. Baseline mean SBP was slightly higher in the eAT group, although both groups means were within the normal range (eAT: 63.6th percentile [23.02 SD] vs. WWSC: 57.6th percentile [26.97 SD]). Mean DBP values were similar between the intervention arms (eAT: 55.4th percentile [20.50 SD] vs. WWSC 52.2nd percentile [21.51]). Both SBP and DBP decreased significantly in the eAT group compared to WWSC (difference between groups: -9.02 for SBP, P = 0.002, 95% CI [-14.77 to -3.28]; and -6.53 for DBP, P = 0.005, 95% CI [-11.02 to -2.03]). Moderation effect analysis indicated that children with overweight/obesity had a larger decrease in DBP percentile following eAT compared to children with a normal BMI at 12 months (-10.41, P = 0.028, 95% CI [-19.69 to -1.12]). At baseline, 53 children (12.2%) had elevated SBP (>90th percentile) and 22 (5.1%) had elevated DBP; 25 (5.8%) had systolic HTN (>95th percentile), and 9 (2.1%) had diastolic HTN. Conclusion: Children with mild oSDB treated with eAT vs. WWSC experienced divergent SBP and DBP trajectories at 12 months, with children in the eAT group experiencing a significant reduction in both SBP and DBP. Moderation effect analysis suggests that children with overweight/obesity may derive greater BP-lowering benefits from adenotonsillectomy.

The literature indicates that health care utilization (HCU) of children with untreated moderate-to-severe obstructive sleep apnea is greater than that of matched controls before diagnosis, and treatment is associated with a decline in HCU not observed in those who remain untreated. Research on this topic has been limited to retrospective analyses and observational cohort studies; little is known about HCU among the many children with snoring and mild sleep-disordered breathing (SDB). To determine whether adenotonsillectomy in comparison with watchful waiting with supportive care is associated with fewer health care encounters and prescriptions. This randomized clinical trial, Pediatric Adenotonsillectomy Trial for Snoring (PATS), was a 12-month, parallel-arm trial conducted from 2016 to 2022 in tertiary care centers in the United States. Participants were recruited from otolaryngology, sleep, pulmonary, or general pediatric clinics; aged 3 to 13 years; diagnosed with mild SDB; had a tonsillar hypertrophy grade of 2 or more; and had a body mass index z score less than 3. Children referred from a clinician outside of the local electronic medical record system were excluded. Data analysis was conducted from June 2022 to April 2024. Early adenotonsillectomy. Evaluation of HCU was a prespecified secondary aim of PATS. Total encounters and total prescriptions over the 12 months after randomization were analyzed. Among 459 children who were randomized, the analytic sample included 381 children, after excluding those referred from outside the local electronic medical record system. The median (IQR) age was 6 (4-8) years; 192 participants (50%) were female and 189 (50%) male. Adenotonsillectomy was associated with a 32% reduction in total health care encounters (mean difference, −1.25 per participant per year; 95% CI, −1.96 to −0.53) and a 48% reduction in prescriptions (mean difference, −2.53 per participant per year; 95% CI, −4.12 to −0.94). The difference in encounters was primarily driven by fewer office visits and outpatient procedures rather than by reduced hospitalizations or urgent care visits. This study found that adenotonsillectomy was associated with reduced all-cause HCU in children with mild SDB, supporting early intervention for children with mild SDB. Future research focused on the cost effectiveness of adenotonsillectomy for pediatric SDB is warranted. ClinicalTrials.gov Identifier: NCT02562040

Importance:The literature indicates that health care utilization (HCU) of children with untreated moderate-to-severe obstructive sleep apnea is greater than that of matched controls before diagnosis, and treatment is associated with a decline in HCU not observed in those who remain untreated. Research on this topic has been limited to retrospective analyses and observational cohort studies; little is known about HCU among the many children with snoring and mild sleep-disordered breathing (SDB). Objective:To determine whether adenotonsillectomy in comparison with watchful waiting with supportive care is associated with fewer health care encounters and prescriptions. Design, Setting, and Participants:This randomized clinical trial, Pediatric Adenotonsillectomy Trial for Snoring (PATS), was a 12-month, parallel-arm trial conducted from 2016 to 2022 in tertiary care centers in the United States. Participants were recruited from otolaryngology, sleep, pulmonary, or general pediatric clinics; aged 3 to 13 years; diagnosed with mild SDB; had a tonsillar hypertrophy grade of 2 or more; and had a body mass index z score less than 3. Children referred from a clinician outside of the local electronic medical record system were excluded. Data analysis was conducted from June 2022 to April 2024. Intervention:Early adenotonsillectomy. Main Outcomes and Measures:Evaluation of HCU was a prespecified secondary aim of PATS. Total encounters and total prescriptions over the 12 months after randomization were analyzed. Results:Among 459 children who were randomized, the analytic sample included 381 children, after excluding those referred from outside the local electronic medical record system. The median (IQR) age was 6 (4-8) years; 192 participants (50%) were female and 189 (50%) male. Adenotonsillectomy was associated with a 32% reduction in total health care encounters (mean difference, -1.25 per participant per year; 95% CI, -1.96 to -0.53) and a 48% reduction in prescriptions (mean difference, -2.53 per participant per year; 95% CI, -4.12 to -0.94). The difference in encounters was primarily driven by fewer office visits and outpatient procedures rather than by reduced hospitalizations or urgent care visits. Conclusions and Relevance:This study found that adenotonsillectomy was associated with reduced all-cause HCU in children with mild SDB, supporting early intervention for children with mild SDB. Future research focused on the cost effectiveness of adenotonsillectomy for pediatric SDB is warranted. Trial Registration:ClinicalTrials.gov Identifier: NCT02562040.

BACKGROUND:Dupilumab demonstrated efficacy in children with asthma in phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies. This post hoc analysis assessed dupilumab's long-term efficacy by asthma severity at parent study baseline. METHODS:Children (6-11 years) with moderate-to-severe type 2 inflammatory asthma (PS baseline blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) from placebo-controlled VOYAGE who enrolled in EXCURSION received dupilumab every 2 weeks for an additional 52 weeks. We assessed annualized severe exacerbation rates, change in pre-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1) and FEV1 z-score, and Interviewer-Administered 7-item Asthma Control Questionnaire (ACQ-7-IA) score in subgroups with moderate (medium-dose inhaled corticosteroid (ICS), pre-bronchodilator percent predicted FEV1 ≥ 80%) and severe (high-dose ICS, pre-bronchodilator percent predicted FEV1 < 80%) asthma at parent study baseline. RESULTS:Among 179 children (104 with moderate, 75 with severe asthma), dupilumab compared to placebo reduced unadjusted annualized severe exacerbation rates during VOYAGE in children with moderate (0.22 vs. 0.37) and severe (0.41 vs. 1.07) asthma, with sustained reductions in EXCURSION (moderate: 0.07 and 0.07; severe: 0.24 and 0.19). At VOYAGE Week 52, the change from the parent study baseline in pre-bronchodilator percent predicted FEV1 was 8.6 versus 2.1 percentage points with dupilumab and placebo in children with moderate asthma, and 16.7 versus 9.8 percentage points in children with severe asthma. Improvements in the change from the parent study baseline in pre-bronchodilator FEV1 z-scores and ACQ-7-IA scores were also observed with dupilumab treatment in both subgroups. CONCLUSION:Long-term dupilumab treatment reduced exacerbation rates and improved lung function and asthma control in children with type 2 asthma irrespective of disease severity, with numerically greater improvements in children with severe asthma.

Introduction Mild sleep-disordered breathing (mSDB) in children is associated with both neurobehavioral morbidity and reduced quality of life (QOL). However, the association between symptom burden and QOL with executive function is not well understood, and it is not known whether QOL and symptom burden may help identify children with neurocognitive dysfunction. Objective To assess associations among executive function, QOL, and symptom burden in children with mSDB. Design, Setting, and Participants This cross-sectional study was a secondary analysis of the multicenter Pediatric Adenotonsillectomy Trial for Snoring, which included children aged 3 to 12 years randomized to watchful waiting or adenotonsillectomy for mSDB (snoring and an obstructive apnea-hypopnea index <3) between June 29, 2016, and February 1, 2021. The data for this report were analyzed between December 22, 2020, and October 3, 2024. Exposure Pediatric mSDB. Main Outcomes and Measures Quality of life was assessed using the Obstructive Sleep Apnea-18 (OSA-18), and symptom burden was assessed using the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder Scale (PSQ-SRBD). Executive function, including self-control and working memory, was measured using the Behavior Rating Inventory of Executive Function Global Executive Composite (BRIEF GEC), and inhibitory control and sustained attention were measured by the GoNoGo vigilance test. Partial Pearson correlations and multiple linear regression models were used to assess the associations among QOL, symptoms, and executive function. Results The sample included 459 children (mean [SD] age, 6.1 [2.3] years; 230 female [50.1%]). Moderate correlations were found between the BRIEF GEC and the PSQ-SRBD and OSA-18 (r = 0.58 [95% CI, 0.51-0.64] and 0.59 [95% CI, 0.52-0.64], respectively). After adjusting for age, sex, race and ethnicity, body mass index percentile, household income, maternal education, attention-deficit/hyperactivity disorder, test characteristics, and disease severity, both OSA-18 and PSQ-SRBD scores were associated with the BRIEF GEC (beta = 0.41 [95% CI, 0.36-0.47] and 3.66 [95% CI, 3.17-4.15], respectively). In the fully adjusted model, PSQ-SRBD was also associated with GoNoGo inhibitory control (beta = -0.04 [95% CI, -0.08 to -0.01]) and sustained attention (beta = -0.05 [95% CI, -0.10 to -0.01]). Conclusions and Relevance In this study, disease-specific QOL and symptom burden were associated with executive function in children with mSDB. These findings may be useful in identifying those children who are at risk for neurocognitive dysfunction.

Rationale: Evidence suggests that asthma duration is associated with more symptoms; early diagnosis and intervention may ameliorate persistent asthma in children. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, central drivers of type 2 inflammation. The VOYAGE trial (NCT02948959) demonstrated the efficacy and safety of dupilumab in children with asthma. This post hoc analysis investigated the association between the efficacy of dupilumab and asthma duration. Methods: VOYAGE was a 52-week double-blind, phase 3 trial of children aged 6-11 years with uncontrolled, moderate-to-severe asthma and randomized 2:1 to dupilumab 100/200 mg (per body weight) or placebo every 2 weeks. Children with type 2 inflammatory asthma (blood eosinophil counts ≥150 cells/μL or fractional exhaled nitric oxide ≥20 parts per billion) were split into three subgroups based on the time between their first asthma diagnosis and enrolment: ≤4 years, >4 to <7 years, and ≥7 years since. Endpoints included proportion of children with no exacerbations over 52 weeks, the adjusted annualized exacerbation rate (AER) throughout, and the proportion with well-controlled asthma (Interviewer-Administered 7-item Asthma Control Questionnaire (ACQ-7-IA) ≤ 0.75) at Week 52. Results: The 350 children were distributed as follows among the asthma duration subgroups: 37.7% on placebo and 31.8% on dupilumab had asthma for ≤4 years; 36.8% on placebo and 36.9% on dupilumab from >4 to <7 years; and 25.4% on placebo and 31.4% on dupilumab for ≥7 years. At the end of VOYAGE, 72.1% on placebo and 86.7% on dupilumab for the ≤4 years group, experienced no severe exacerbations (P = 0.0439) compared with 54.8% on placebo and 71.3% on dupilumab (P = 0.0359) for the >4 to <7 years group, and 48.3% on placebo and 74.3% on dupilumab (P = 0.0046) for the ≥7 years group. Children on dupilumab demonstrated significant decreases in adjusted AER compared to placebo (Figure). Well-controlled asthma was reported in 55.8% on placebo and 78.7% on dupilumab (P = 0.0110) for the ≤4 years group, 42.9% on placebo and 67.8% on dupilumab (P = 0.0104) for the >4 to <7 years group, and 34.5% on placebo and 62.2% on dupilumab (P = 0.0189) for the ≥7 years group. Conclusion: Dupilumab decreased exacerbations and improved asthma control compared to placebo in children with uncontrolled moderate-to-severe type 2 asthma regardless of disease duration. Longer asthma duration was associated with more exacerbations and less disease control.

Pediatric PulmonologyEarly View LETTER The effect of adenotonsillectomy on asthma symptoms in the Pediatric Adenotonsillectomy Trial for Snoring (PATS) Seyni Gueye-Ndiaye MD, Corresponding Author Seyni Gueye-Ndiaye MD [email protected] orcid.org/0000-0002-0907-9224 Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Correspondence Seyni Gueye-Ndiaye, MD, Division of Pulmonary Medicine, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA. Email: [email protected] Contribution: Writing - original draft, Writing - review & editing, Methodology, ​Investigation, ConceptualizationSearch for more papers by this authorMeg Tully MBiostat, Meg Tully MBiostat Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Formal analysis, Writing - review & editing, Visualization, Methodology, ConceptualizationSearch for more papers by this authorPo-Yang Tsou MD, Po-Yang Tsou MD Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Conceptualization, Writing - review & editing, ​Investigation, MethodologySearch for more papers by this authorRaouf Amin MD, Raouf Amin MD Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorCristina M. Baldassari MD, Cristina M. Baldassari MD Division of Sleep Medicine, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, Children's Hospitals of The King's Daughters, Norfolk, Virginia, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorRonald D. Chervin MD, MS, Ronald D. Chervin MD, MS Department of Neurology, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorChristopher M. Cielo DO, Christopher M. Cielo DO Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorAlisha George MD, Alisha George MD Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorFauziya Hassan MD, Fauziya Hassan MD Department of Pediatrics, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorSally Ibrahim MD, Sally Ibrahim MD Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorStacey L. Ishman MD, MPH, Stacey L. Ishman MD, MPH Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorErin M. Kirkham MD, MPH, Erin M. Kirkham MD, MPH Department of Otolaryngology-Head and Neck Surgery, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Writing - review & editing, Methodology, ConceptualizationSearch for more papers by this authorRon B. Mitchell MD, Ron B. Mitchell MD Children's Medical Center of Dallas and UT Southwestern Medical Center, Dallas, Texas, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorKamal Naqvi MD, Kamal Naqvi MD Children's Medical Center of Dallas and UT Southwestern Medical Center, Dallas, Texas, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorMoshe Prero MD, Moshe Prero MD Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorMichael Rueschman MPH, Michael Rueschman MPH Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Writing - review & editing, Methodology, Conceptualization, Project administration, Data curationSearch for more papers by this authorIgnacio E. Tapia MD, Ignacio E. Tapia MD orcid.org/0000-0003-1400-6852 University of Miami Health System and Miller School of Medicine, Miami, Florida, USA Contribution: Writing - review & editing, Conceptualization, MethodologySearch for more papers by this authorCarlos Sendon MD, Carlos Sendon MD Division of Sleep Medicine, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, Children's Hospitals of The King's Daughters, Norfolk, Virginia, USA Contribution: Writing - review & editing, Methodology, ConceptualizationSearch for more papers by this authorRui Wang PhD, Rui Wang PhD Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA Contribution: Supervision, Writing - review & editing, Methodology, Formal analysis, Conceptualization, ​Investigation, ResourcesSearch for more papers by this authorSusan Redline MD, MPH, Susan Redline MD, MPH Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Supervision, Conceptualization, ​Investigation, Funding acquisition, Writing - review & editing, Methodology, ResourcesSearch for more papers by this authorKristie Ross MD, Kristie Ross MD orcid.org/0000-0001-7732-2516 Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, ​Investigation, Methodology, Writing - review & editing, SupervisionSearch for more papers by this author Seyni Gueye-Ndiaye MD, Corresponding Author Seyni Gueye-Ndiaye MD [email protected] orcid.org/0000-0002-0907-9224 Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Correspondence Seyni Gueye-Ndiaye, MD, Division of Pulmonary Medicine, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA. Email: [email protected] Contribution: Writing - original draft, Writing - review & editing, Methodology, ​Investigation, ConceptualizationSearch for more papers by this authorMeg Tully MBiostat, Meg Tully MBiostat Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Formal analysis, Writing - review & editing, Visualization, Methodology, ConceptualizationSearch for more papers by this authorPo-Yang Tsou MD, Po-Yang Tsou MD Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Conceptualization, Writing - review & editing, ​Investigation, MethodologySearch for more papers by this authorRaouf Amin MD, Raouf Amin MD Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorCristina M. Baldassari MD, Cristina M. Baldassari MD Division of Sleep Medicine, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, Children's Hospitals of The King's Daughters, Norfolk, Virginia, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorRonald D. Chervin MD, MS, Ronald D. Chervin MD, MS Department of Neurology, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorChristopher M. Cielo DO, Christopher M. Cielo DO Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorAlisha George MD, Alisha George MD Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorFauziya Hassan MD, Fauziya Hassan MD Department of Pediatrics, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorSally Ibrahim MD, Sally Ibrahim MD Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorStacey L. Ishman MD, MPH, Stacey L. Ishman MD, MPH Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorErin M. Kirkham MD, MPH, Erin M. Kirkham MD, MPH Department of Otolaryngology-Head and Neck Surgery, Michigan Medicine, Ann Arbor, Michigan, USA Contribution: Writing - review & editing, Methodology, ConceptualizationSearch for more papers by this authorRon B. Mitchell MD, Ron B. Mitchell MD Children's Medical Center of Dallas and UT Southwestern Medical Center, Dallas, Texas, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorKamal Naqvi MD, Kamal Naqvi MD Children's Medical Center of Dallas and UT Southwestern Medical Center, Dallas, Texas, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorMoshe Prero MD, Moshe Prero MD Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, Methodology, Writing - review & editingSearch for more papers by this authorMichael Rueschman MPH, Michael Rueschman MPH Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Writing - review & editing, Methodology, Conceptualization, Project administration, Data curationSearch for more papers by this authorIgnacio E. Tapia MD, Ignacio E. Tapia MD orcid.org/0000-0003-1400-6852 University of Miami Health System and Miller School of Medicine, Miami, Florida, USA Contribution: Writing - review & editing, Conceptualization, MethodologySearch for more papers by this authorCarlos Sendon MD, Carlos Sendon MD Division of Sleep Medicine, Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, Children's Hospitals of The King's Daughters, Norfolk, Virginia, USA Contribution: Writing - review & editing, Methodology, ConceptualizationSearch for more papers by this authorRui Wang PhD, Rui Wang PhD Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA Contribution: Supervision, Writing - review & editing, Methodology, Formal analysis, Conceptualization, ​Investigation, ResourcesSearch for more papers by this authorSusan Redline MD, MPH, Susan Redline MD, MPH Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA Contribution: Supervision, Conceptualization, ​Investigation, Funding acquisition, Writing - review & editing, Methodology, ResourcesSearch for more papers by this authorKristie Ross MD, Kristie Ross MD orcid.org/0000-0001-7732-2516 Rainbow Babies and Children's Hospital and University Hospitals, Cleveland, Ohio, USA Contribution: Conceptualization, ​Investigation, Methodology, Writing - review & editing, SupervisionSearch for more papers by this author First published: 24 April 2024 https://doi.org/10.1002/ppul.27022Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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Schools are in a unique position to address social determinants of health (SDOHs) in pediatric asthma management because of their potential to provide resources and facilitate collaboration with health care providers and services for children at risk within their community. SDOHs include economic factors, educational attainment and health literacy, neighborhood factors and the built environment, social and community aspects including discrimination and racism, and health care access and quality. These factors have a significant impact on asthma health in children, and certain populations such as minoritzed populations and those living in high-poverty environments have been shown to be at greater risk for adverse effects of SDOHs on asthma outcomes. School-based asthma programs address several SDOHs including health literacy, the built environment, and health care quality and access and have been shown to improve asthma outcomes. Key components include connection between the school and the health care team, self-management education, and directly observed therapy. School nurses play a key role in directing and managing effective programs because they can evaluate and support a student's health while considering the effect of SDOHs at interpersonal, institutional, community, and policy levels.

ImportanceIt is unknown whether adenotonsillectomy causes undesirable weight gain in children with mild obstructive sleep-disordered breathing (oSDB).ObjectiveTo compare changes in anthropometric measures in children with mild oSDB treated with adenotonsillectomy vs watchful waiting.Design, Setting, and ParticipantsThis was an exploratory analysis of the Pediatric Adenotonsillectomy Trial for Snoring (PATS) randomized clinical trial of adenotonsillectomy vs watchful waiting for mild oSDB (snoring with obstructive apnea-hypopnea index of <3 events/hour) that took place at 7 pediatric tertiary care centers across the US and included 458 children aged 3.0 to 12.9 years with mild oSDB. Participants were recruited from June 29, 2016, to February 1, 2021. Anthropomorphic measures taken at baseline and 12 months after randomization were standardized for age and sex, including each participant’s percentage of the 95th body mass index percentile (%BMIp95). Data analyses were performed from March 15, 2023, to April 1, 2024.InterventionEarly adenotonsillectomy (eAT) vs watchful waiting with supportive care (WWSC).Main Outcomes and MeasuresTwelve-month change in %BMIp95 from baseline and undesirable weight gain (defined as any weight gain in a child who already had overweight or obesity or an increase from baseline normal weight/underweight to overweight/obesity) at follow-up assessment.ResultsThe study analysis included 375 children (mean [SD] age, 6.1 [2.3] years; 188 [50.2%] females), of whom 143 (38%) had overweight or obesity at baseline. At 12 months, children in the eAT group experienced a 1.25-point increase in %BMIp95 compared with a 0.59-point increase in the WWSC group (mean difference, 0.93; 95% CI, −0.39 to 2.25). Undesirable weight gain was also similar between the eAT (n = 120; 32%) and WWSC (n = 101; 27%) groups (mean difference, 4%; 95% CI, 5% to 14%).Conclusions and RelevanceThe findings of this exploratory analysis of the PATS trial indicate that adenotonsillectomy was not independently associated with an increased risk of undesirable weight gain in children with mild oSDB. However, one-third of the children gained undesirable weight during the study, which suggests that there is an opportunity to address healthy weight management during the evaluation and treatment of children with mild oSDB.Trial RegistrationClinicalTrials.gov Identifier: NCT02562040

Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils >= 150 cells/mu L or fractional exhaled nitric oxide >= 20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (>= 5% or >= 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV(1)) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV(1) to Week 12. Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of >= 5% in ppFEV(1); 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV(1) >= 10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV(1) (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of >= 5%. Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV(1), with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV(1) response at Week 12.

Although asthma is common in children with sleep-disordered breathing (SDB), it is unclear whether and to what extent asthma is associated with SDB-related outcomes. Our objectives are to describe risk factors for asthma among children with mild SDB (mSDB) and assess the association between asthma and the severity of sleep-related outcomes. Cross-sectional analyses were conducted for children aged 3–12.9 years with mSDB enrolled in Pediatric Adenotonsillectomy for Snoring Children Study. Sleep-related outcomes included SDB symptoms (Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder scale (PSQ-SRBD)), SDB-specific quality of life (OSA-18), sleepiness (modified Epworth Sleepiness Score) and polysomnographic and actigraphic measures. Asthma was defined by caregiver-reported diagnosis with current asthma symptoms and medication use, or a Composite Asthma Severity Index (CASI) score ≥ 4. Asthma was further categorized into mild (CASI < 4) and moderate-to-severe (CASI ≥ 4). Regression analyses were conducted to identify asthma risk factors and estimate the associations between mild and moderate-to-severe asthma with sleep-related outcomes. The sample included 425 children (20.3 β adj; 95 β adj; 95 β adj; 95 https://clinicaltrials.gov/study/NCT02562040

Importance:It is unknown whether adenotonsillectomy causes undesirable weight gain in children with mild obstructive sleep-disordered breathing (oSDB). Objective:To compare changes in anthropometric measures in children with mild oSDB treated with adenotonsillectomy vs watchful waiting. Design, Setting, and Participants:This was an exploratory analysis of the Pediatric Adenotonsillectomy Trial for Snoring (PATS) randomized clinical trial of adenotonsillectomy vs watchful waiting for mild oSDB (snoring with obstructive apnea-hypopnea index of <3 events/hour) that took place at 7 pediatric tertiary care centers across the US and included 458 children aged 3.0 to 12.9 years with mild oSDB. Participants were recruited from June 29, 2016, to February 1, 2021. Anthropomorphic measures taken at baseline and 12 months after randomization were standardized for age and sex, including each participant's percentage of the 95th body mass index percentile (%BMIp95). Data analyses were performed from March 15, 2023, to April 1, 2024. Intervention:Early adenotonsillectomy (eAT) vs watchful waiting with supportive care (WWSC). Main Outcomes and Measures:Twelve-month change in %BMIp95 from baseline and undesirable weight gain (defined as any weight gain in a child who already had overweight or obesity or an increase from baseline normal weight/underweight to overweight/obesity) at follow-up assessment. Results:The study analysis included 375 children (mean [SD] age, 6.1 [2.3] years; 188 [50.2%] females), of whom 143 (38%) had overweight or obesity at baseline. At 12 months, children in the eAT group experienced a 1.25-point increase in %BMIp95 compared with a 0.59-point increase in the WWSC group (mean difference, 0.93; 95% CI, -0.39 to 2.25). Undesirable weight gain was also similar between the eAT (n = 120; 32%) and WWSC (n = 101; 27%) groups (mean difference, 4%; 95% CI, 5% to 14%). Conclusions and Relevance:The findings of this exploratory analysis of the PATS trial indicate that adenotonsillectomy was not independently associated with an increased risk of undesirable weight gain in children with mild oSDB. However, one-third of the children gained undesirable weight during the study, which suggests that there is an opportunity to address healthy weight management during the evaluation and treatment of children with mild oSDB. Trial Registration:ClinicalTrials.gov Identifier: NCT02562040.

Rationale: Neighborhood disadvantage (ND) has been associated with sleep-disordered breathing (SDB) in children. However, the association between ND and SDB symptom burden and quality of life (QOL) has not yet been studied.Objectives: To evaluate associations between ND with SDB symptom burden and QOL.Methods: Cross-sectional analyses were performed on 453 children, ages 3-12.9 years, with mild SDB (habitual snoring and apnea-hypopnea index < 3/h) enrolled in the PATS (Pediatric Adenotonsillectomy Trial for Snoring) multicenter study. The primary exposure, neighborhood disadvantage, was characterized by the Child Opportunity Index (COI) (range, 0-100), in which lower values (specifically COI ⩽ 40) signify less advantageous neighborhoods. The primary outcomes were QOL assessed by the obstructive sleep apnea (OSA)-18 questionnaire (range, 18-126) and SDB symptom burden assessed by the Pediatric Sleep Questionnaire-Sleep-related Breathing Disorder (PSQ-SRBD) scale (range, 0-1). The primary model was adjusted for age, sex, race, ethnicity, maternal education, recruitment site, and season. In addition, we explored the role of body mass index (BMI) percentile, environmental tobacco smoke (ETS), and asthma in these associations.Results: The sample included 453 children (16% Hispanic, 26% Black or African American, 52% White, and 6% other). COI mean (standard deviation [SD]) was 50.3 (29.4), and 37% (n = 169) of participants lived in disadvantaged neighborhoods. Poor SDB-related QOL (OSA-18 ⩾ 60) and high symptom burden (PSQ-SRBD ⩾ 0.33) were found in 30% (n = 134) and 75% (n = 341) of participants, respectively. In adjusted models, a COI increase by 1 SD (i.e., more advantageous neighborhood) was associated with an improvement in OSA-18 score by 2.5 points (95% confidence interval [CI], -4.34 to -0.62) and in PSQ-SRBD score by 0.03 points (95% CI, -0.05 to -0.01). These associations remained significant after adjusting for BMI percentile, ETS, or asthma; however, associations between COI and SDB-related QOL attenuated by 23% and 10% after adjusting for ETS or asthma, respectively.Conclusions: Neighborhood disadvantage was associated with poorer SDB-related QOL and greater SDB symptoms. Associations were partially attenuated after considering the effects of ETS or asthma. The findings support efforts to reduce ETS and neighborhood-level asthma-related risk factors and identify other neighborhood-level factors that contribute to SDB symptom burden as strategies to address sleep-health disparities.Clinical trial registered with www.clinicaltrials.gov (NCT02562040).

BACKGROUND:Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children.OBJECTIVE:Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency.METHODS:We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository.RESULTS:Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth.CONCLUSION:These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.