Assessing the Role of Asthma on the Relationship between Neurodevelopmental Disabilities and Adverse Birth Outcomes.

BACKGROUND: Investigating asthma as an effect modifier between adverse birth outcomes and neurodevelopmental disabilities (NDDs) across different races is crucial for tailored interventions and understanding variable susceptibility among diverse populations. METHODS: Data were collected through the National Survey of Children's Health. This cross-sectional study included 131,774 children aged 0 to 17 years. Study exposures comprised adverse birth outcomes including preterm birth and low birth weight. Weighted prevalence estimates and odds ratios with 95% confidence intervals (CIs) among children with and without adverse birth outcomes were calculated for NDDs including attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, seizure, and several others including behavior problems. Adjusted odds ratios were stratified by asthma status and separate interactions were assessed for each outcome. RESULTS: Of 131,774 participants, 10,227 were born low birth weight (9.12%; 95% CI: 8.77% to 9.49%), 14,058 were born preterm (11.35%; 95% CI: 10.94% to 11.76%), and 16,166 participants had asthma (11.97%; 95% CI: 11.58% to 12.37%). There were 68,100 males (51.11%), 63,674 females (48.89%), 102,061 non-Hispanic Whites (NHW) (66.92%), 8,672 non-Hispanic Blacks (NHB) (13.97%), and 21,041 participants (19.11%) categorized as other. NHB children with adverse birth outcomes had higher prevalence of several NDDs compared to NHW children. CONCLUSIONS: Asthma was not shown to be an effect modifier of the association between adverse birth outcomes and NDDs. Nevertheless, these results suggest that NDDs are more prevalent within US children with adverse birth outcomes, with higher rates among NHB compared to NHW children. These findings support screening for NDDs in pediatric health care settings among patients with adverse birth outcomes, particularly among those from ethnic minority backgrounds.

Association between asthma, obesity, and metabolic syndrome in adolescents and young adults.

BACKGROUND: The association of asthma and metabolic syndrome (MetS) among adolescents and young adults (AYAs) remains unclear, as well as the role of obesity in this relationship. METHODS: AYAs aged 12-25 years who participated in the 2011-2020 National Health and Nutrition Examination Survey were included in this cross-sectional analysis. The moderating effect of obesity (age- and sex-adjusted body mass index ≥ 95th%ile for adolescents or ≥ 30 kg/m2 for adults) on asthma and MetS were evaluated in four groups: 1) both asthma and obesity; 2) asthma and no obesity; 3) obesity and no asthma; and 4) healthy controls with no obesity/asthma. RESULTS: A total of 7,709 AYAs (53.9% aged 12-18 years, 51.1% males, and 54.4% non-Hispanic White) were included in this analysis. 3.6% (95% CI 2.8-4.3%) had obesity and asthma, 7.6% (95% CI 6.8-8.4%) had asthma and no obesity, 21.4% (95% CI 19.6-23.2%) had obesity and no asthma, and 67.4% (95% CI 65.4-69.4%) had neither obesity nor asthma. The estimated prevalence of MetS was greater among those with both obesity and asthma versus those with only asthma (4.5% [95% CI 1.7-7.3%] vs. 0.2% [95% CI 0-0.5%], p < 0.001). Compared to healthy controls, those with both obesity and asthma had ∼10 times higher odds of having MetS (aOR 10.5, 95% CI 3.9-28.1). CONCLUSIONS: Our results show the association between MetS and asthma is stronger in AYAs with BMI-defined obesity. Efforts to prevent and treat obesity may reduce MetS occurrence in AYAs with asthma.

Association of corticosteroid use and attention deficit/hyperactivity disorder in asthmatic children varies by age.

OBJECTIVE: We aim to examine the impact of corticosteroids use on ADHD among children with asthma by administration routes. METHODS: A population-based, cross-sectional analysis included pediatric patients ages 5-20 years old from the 2016 and 2019 Kids Inpatient Database (unweighted N = 111,702). ICD-10-CM codes were used to identify corticosteroids use, asthma, and ADHD cases. Survey logistic regression models with purposeful variable selection algorithms were built to examine the association between corticosteroids use, and ADHD by asthma severity and age. An inverse probability weighting (IPW) approach was used to help further control residual confounding. RESULTS: Among children aged 5-11 years old, the odds of ADHD were significantly higher in children with moderate to severe asthma who used inhaled corticosteroids than nonusers (moderate asthma: adjusted odds ratios [aOR] 1.46, 95% confidence interval [CI] 1.14-2.44; severe asthma: aOR 1.61, 95% CI 1.18-2.21). Although oral corticosteroid use was not independently associated with ADHD in young children, combined use of inhaled and oral corticosteroid had almost 5 times higher odds of use among ADHD in children with severe asthma vs. nonusers (aOR 4.85, 95% CI 2.07 - 11.35). No associations were found between any corticosteroid use and ADHD among asthmatic children aged 12-20 years. CONCLUSIONS: In this retrospective analysis, we found inhaled corticosteroids were positively associated with ADHD in younger children with moderate to severe asthma, but not in older children.

Prevalence of polypharmacy and associated adverse outcomes and risk factors among children with asthma in the USA: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of polypharmacy, identify risk factors and examine related adverse outcomes in the US children with asthma. DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 1776 children with asthma from the 2011-2020 National Health and Nutrition Examination Surveys. EXPOSURES: Polypharmacy is defined as taking ≥2 medications concurrently for ≥1 day over the past 30 days. MAIN OUTCOMES AND MEASURES: (1) Weighted prevalence estimates of polypharmacy in children with asthma; (2) asthma attacks and emergency department (ED) visits. RESULTS: The estimated prevalence of polypharmacy in the US children with asthma was 33.49% (95% CI 31.81% to 35.17%). 15.53% (95% CI 14.31% to 16.75%), 12.63% (95% CI 11.37% to 13.88%) and 5.33% (95% CI) of participants were taking 2, 3-4, and 5 prescription medications, respectively. In addition to asthma medications, the most common sources of polypharmacy included antihistamines (20.17%, 95% CI 16.07% to 24.28%), glucocorticoids (16.67%, 95% 12.57% to 20.78%), and anti-infectives (14.28%, 95% CI 10.29 to 18.28). Risk factors for the increased number of medications included age 5-11 years old (vs 1-4 years: adjusted incidence rate ratio (aIRR) 1.38, 95% CI 1.10 to 1.72), fair-to-poor health (vs excellent or very good: aIRR 1.42, 95% CI 1.05 to 1.92), or ≥6 healthcare utilisation encounters over the last year (vs 0-5 encounters: aIRR 1.45, 95% CI 1.26 to 1.66). Polypharmacy increased the odds of an asthma attack (adjusted OR (aOR) 2.80, 95% CI 1.99 to 3.93) and ED visit (aOR 2.41, 95%1.59-3.63) after adjusting for demographics, insurance and health status. CONCLUSIONS: Every one in three US children with asthma experienced polypharmacy. Although it may reflect the treatment guidelines that various asthma medications are needed for maintenance therapy, our results suggested that polypharmacy increased the odds of asthma attacks or ED visits. This may be due to the concurrent use with other non-asthma medications indicating that there is an opportunity to improve medication management in children with asthma.

Adverse Drug Events Related to Common Asthma Medications in US Hospitalized Children, 2000-2016.

BACKGROUND: The reduction in adverse drug events is a priority in healthcare. Medications are frequently prescribed for asthmatic children, but epidemiological trends of adverse drug events related to anti-asthmatic medications have not been described in hospitalized children. OBJECTIVE: The objective of this study was to report incidence trends, risk factors, and healthcare utilization of adverse drug events related to anti-asthmatic medications by major drug classes in hospitalized children in the USA from 2000 to 2016. METHODS: A population-based temporal analysis included those aged 0-20 years who were hospitalized with asthma from the 2000 to 2016 Kids Inpatient Database. Age-stratified weighted temporal trends of the inpatient incidence of adverse drug events related to anti-asthmatic medications (i.e., corticosteroids and bronchodilators) were estimated. Stepwise multivariate logistic regression models generated risk factors for adverse drug events. RESULTS: From 2000 to 2016, 12,640 out of 698,501 pediatric asthma discharges (1.7%) were associated with adverse drug events from anti-asthmatic medications. 0.83% were adverse drug events from corticosteroids, resulting in a 1.14-fold increase in the length of stay (days) and a 1.42-fold increase in hospitalization charges (dollars). The overall incidence (per 1000 discharges) of anti-asthmatic medication adverse drug events increased from 5.3 (95% confidence interval [CI] 4.6-6.1) in 2000 to 21.6 (95% CI 18.7-24.6) in 2016 (p-trend = 0.024). Children aged 0-4 years had the most dramatic increase in the incidence of bronchodilator adverse drug events from 0.2 (95% CI 0.1-0.4) to 19.3 (95% CI 15.2-23.4) [p-trend ≤ 0.001]. In general, discharges among asthmatic children with some comorbidities were associated with an approximately two to five times higher odds of adverse drug events. CONCLUSIONS: The incidence of adverse drug events from common anti-asthmatic medications quadrupled over the past decade, particularly among preschool-age children who used bronchodilators, resulting in substantial increased healthcare costs. Those asthmatic children with complex medical conditions may benefit the most from adverse drug event monitoring.

Association between asthma and sugar-sweetened beverage consumption in the United States pediatric population.

OBJECTIVES: United States (US) youth consume an average of 10 teaspoons of added sugar from sugar-sweetened beverages (SSB) on any given day. Few population-based studies have examined the association between SSB consumption and asthma in children and adolescents. This study aimed to examine the association between SSB consumption and asthma in the US pediatric population. DESIGN: Analytical cross-sectional study. SETTING AND PARTICIPANTS: A total of 9,938 children aged 2-to-17 years old who participated in the 2011-2016 National Health and Nutrition Examination Surveys. SSB consumption was categorized into 3 groups based on the caloric intake from 24-hour food recall data as follows: 1) no consumption (0 kcal/day); 2) moderate consumption (1-499 kcal/day); and 3) heavy consumption (≥ 500 kcal/day). The primary outcome of interest was self-reported current asthma condition. RESULTS: Asthma prevalence estimates were significantly higher in heavy (16.4%) and moderate (11.0%) SSB consumers versus non-consumers (7.5%) (p < 0.05 for both comparisons). The adjusted odds of asthma were twice that among children with heavy SSB consumption (aOR 2.01, 95% confidence interval [CI] 1.31-3.08) versus non-SSB consumers. The odds of asthma were higher among those who consumed fruit drinks (aOR 2.51, 95% CI 1.55-4.08), non-diet soft drinks (aOR 1.89, 95% CI 1.23-2.89) and sweet tea (aOR 1.87, 95% CI 1.13-3.09) compared to nondrinkers. The effect was independent of obesity status (p-interaction = 0.439). CONCLUSIONS: Findings here suggest a dose-response relationship between SSB intake and asthma diagnosis, therefore controlling SSB consumption may potentially improve pulmonary health risk in the US pediatric population.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

United States prevalence of pediatric asthma by environmental tobacco smoke exposure, 2016-2017.

OBJECTIVES: We sought to update the prevalence estimates of parent-reported asthma diagnosis by Environmental Tobacco Smoke (ETS) exposure in the United States (US) pediatric population. METHODS: This cross-sectional study included 71,811 families with children who participated in the 2016-2017 National Survey of Children's Health (NSCH). Weighted asthma prevalence estimates were calculated for ETS-exposed and non-exposed children. Chi-square analysis compared asthma prevalence between the two exposure groups and logistic regression analysis generated adjusted odds ratios (aORs) of asthma diagnosis by ETS exposure by sex, race/ethnicity, and household education and income level. RESULTS: Asthma prevalence estimates were significantly higher in ETS-exposed vs. non-exposed children (10.7% vs. 7.8%, p < 0.001). Children with a smoker in the house are 30% more likely to have an asthma diagnosis vs. children with no smokers in the house (aOR 1.29, 95% Confidence Interval [CI] 1.09-1.52). Significant predictors for ETS exposure included < high school education and lower family income. Conversely, non-Hispanic black and Hispanic children were less likely to have ETS exposure vs. non-Hispanic white children. CONCLUSIONS: ETS exposure is a significant risk factor for asthma in the US pediatric population. Smoking cessation initiatives targeting non-Hispanic white parents from lower socioeconomic may improve children's chronic pulmonary health risk.

Disseminated Nannizziopsis Infection in an Adolescent With a STAT1 Mutation.

An adolescent with failure to thrive developed cuboid bone osteomyelitis and brain abscesses. Mold isolated from both locations was identified by universal genetic sequencing as Nannizziopsis spp, which is typically a pathogen of reptiles. The patient was subsequently diagnosed with a STAT1 mutation and was successfully treated.

Estimated Prevalence of Asthma in US Children With Developmental Disabilities.

Importance: The prevalence of asthma in US children with various developmental disabilities and delays is unclear, including how estimates vary by ethnic group. Objective: To report asthma prevalence estimates by various disability categories and developmental delays in a diverse sample of the US pediatric population. Design, Setting, and Participants: This population-based cross-sectional study encompassed a total of 71 811 families with children or adolescents aged 0 to 17 years (hereinafter referred to as children) who participated in the 2016 and 2017 National Survey of Children's Health. Data were collected from June 10, 2016, to February 10, 2017, for the 2016 survey and from August 10, 2017, to February 10, 2018, for the 2017 survey. Data were analyzed from September 20, 2019, to April 5, 2020. Exposures: Developmental disability, including attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, seizure, intellectual and/or learning disability, and vision, hearing, and/or speech delay. Delay was defined as not meeting growth milestones with unknown cause. Main Outcomes and Measures: Weighted asthma prevalence estimates and 95% CIs were generated for children with and without disabilities. Results: A total of 71 811 participants (mean [SE] age, 8.6 [0.1] years; 36 800 boys [51.1%; 95% CI, 50.2%-52.0%]; 50 219 non-Hispanic white [51.4%; 95% CI, 50.6%-52.3%]) were included in our final analytical sample, of whom 5687 (7.9%; 95% CI, 7.5%-8.4%) had asthma and 11 426 (15.3%; 95% CI, 14.7%-16.0%) had at least 1 disability. Overall asthma prevalence estimates were 10 percentage points higher in children with a disability (16.1%; 95% CI, 14.3%-17.8%) vs children without a disability (6.5%; 95% CI, 6.0%-6.9%). The odds of asthma were significantly higher in children with a disability (odds ratio [OR], 2.77; 95% CI, 2.39-3.21) or delay (OR, 2.22; 95% CI, 1.78-2.77) vs typically growing children. Adjusted models remained significant for all disability categories (overall adjusted OR, 2.21; 95% CI, 1.87-2.62). Subgroup analyses showed ethnic minorities had a higher prevalence of concurrent asthma and developmental disabilities vs non-Hispanic whites (19.8% [95% CI, 16.6%-23.0%] vs 12.6% [95% CI, 11.1%-14.0%]; P < .001). Conclusions and Relevance: These results suggest that US children with various developmental disabilities or delay may have higher odds for developing asthma vs their typically developing peers. These findings support asthma screening in pediatric health care settings among patients with developmental disabilities and delays, particularly among those from ethnic minority backgrounds. In addition, very young children with asthma should be screened for disabilities and delays, because temporality cannot be determined by the current data source and analytical approach.

Expanding the phenotype of congenital central hypoventilation syndrome impacts management decisions.

Congenital central hypoventilation syndrome (CCHS) is a neurocristopathy caused by pathogenic heterozygous variants in the gene paired-like homeobox 2b (PHOX2B). It is characterized by severe infantile alveolar hypoventilation. Individuals may also have diffuse autonomic nervous system dysfunction, Hirschsprung disease and neural crest tumors. We report three individuals with CCHS due to an 8-base pair duplication in PHOX2B; c.691_698dupGGCCCGGG (p.Gly234Alafs*78) with a predominant enteral and neural crest phenotype and a relatively mild respiratory phenotype. The attenuated respiratory phenotype reported here and elsewhere suggests an emergent genotype:phenotype correlation which challenges the current paradigm of invoking mechanical ventilation for all infants diagnosed with CCHS. Best treatment requires careful clinical judgment and ideally the assistance of a care team with expertise in CCHS.