Human microbiome variation associated with race and ethnicity emerges as early as 3 months of age.

Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes racial and ethnic categories with 87% accuracy. Importantly, predictive genera are also among the top 30 most important taxa when childhood microbiomes are used to predict adult self-identified race and ethnicity. Our results highlight a critical developmental window at or shortly after 3 months of age when social and environmental factors drive race and ethnicity-associated microbiome variation and may contribute to adult health and health disparities.

Nasopharyngeal airway long noncoding RNAs of infants with bronchiolitis and subsequent risk of developing childhood asthma.

BACKGROUND: Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for developing childhood asthma. However, the biological mechanisms linking these 2 conditions remain unclear. OBJECTIVE: We sought to investigate the longitudinal relationship between nasopharyngeal airway long noncoding RNA (lncRNA) in infants with severe bronchiolitis and subsequent asthma development. METHODS: In this multicenter prospective cohort study of infants with severe bronchiolitis, we performed RNA sequencing of nasopharyngeal airway lncRNAs at index hospitalization. First, we identified differentially expressed lncRNAs (DE-lncRNAs) associated with asthma development by age 6 years. Second, we investigated the associations of DE-lncRNAs with asthma-related clinical characteristics. Third, to characterize the function of DE-lncRNAs, we performed pathway analysis for mRNA targeted by DE-lncRNAs. Finally, we examined the associations of DE-lncRNAs with nasal cytokines at index hospitalization. RESULTS: Among 343 infants with severe bronchiolitis (median age, 3 months), we identified 190 DE-lncRNAs (false-discovery rate [FDR] < 0.05) associated with asthma development (eg, LINC02145, RAMP2-AS1, and PVT1). These DE-lncRNAs were associated with asthma-related clinical characteristics (FDR < 0.05), for example, respiratory syncytial virus or rhinovirus infection, infant eczema, and IgE sensitization. Furthermore, DE-lncRNAs were characterized by asthma-related pathways, including mitogen-activated protein kinase, FcɛR, and phosphatidylinositol 3-kinase (PI3K)-protein kinase B signaling pathways (FDR < 0.05). These DE-lncRNAs were also associated with nasal cytokines (eg, IL-1ß, IL-4, and IL-13; FDR < 0.05). CONCLUSIONS: In a multicenter cohort study of infants with severe bronchiolitis, we identified nasopharyngeal airway lncRNAs associated with childhood asthma development, characterized by asthma-related clinical characteristics, asthma-related pathways, and nasal cytokines. Our approach identifies lncRNAs underlying the bronchiolitis-asthma link and facilitates the early identification of infants at high risk of subsequent asthma development.

Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. RESULTS: Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. CONCLUSIONS: In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts.

OBJECTIVE: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. STUDY DESIGN: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines. RESULTS: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts. CONCLUSIONS: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

A systematic review and meta-analysis on absolute eosinophil counts and the risk of asthma in preschool children with wheezing: An EAACI Task Force Report.

Preschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45-7.98, p = .38), 2.87 (95% CI: 1.38-5.95, p < .05), and 3.38 (95% CI: 1.72-6.64, p < .05) for cutoff values in the <300, 300-449, and ≥450 cells/µL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/µL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.

Asthma heterogeneity among Asian American children: The California Health Interview Survey.

BACKGROUND: The Asian American (AsA) population is heterogenous and rapidly growing; however, little is known regarding childhood asthma burden among AsA ethnic groups. The relation between obesity and asthma in AsA ethnic groups also remains unclear. OBJECTIVE: To evaluate asthma prevalence and the relation of obesity to asthma risk among children in 7 AsA ethnic groups. METHODS: We analyzed data from the California Health Interview Survey from 2011 to 2020. AsA ethnicities were self-reported. Body mass index z-scores, calculated from self-reported height/weight, were used to categorize children by obesity status, based on body mass index-for-age growth charts. Prevalence of self-reported lifetime doctor-diagnosed asthma and asthma attack in the last 12 months was calculated. We performed multivariable logistic regressions adjusting for age and sex. RESULTS: Of 34,146 survey respondents, 12.2% non-Hispanic White and 12.5% AsA children reported lifetime asthma. Among AsA ethnic groups, however, lifetime asthma ranged from 5.1% (Korean American) to 21.5% (Filipino American). Non-Hispanic White children and AsA children had a similar lifetime asthma prevalence (adjusted odds ratio [aOR], 1.05; 95% CI, 0.71-1.55; P = .81), but prevalence was lower in Korean American children (aOR, 0.37; 95% CI, 0.19-0.73; P = .004) and higher in Filipino American children (aOR, 1.97; 95% CI, 1.22-3.17; P = .006). The lifetime asthma prevalence of different AsA ethnic groups persisted even when stratified by obesity status. CONCLUSION: Childhood lifetime asthma prevalence varied among AsA ethnic groups, with lowest prevalence in Korean American children and highest prevalence in Filipino American. Further characterization of asthma burden among AsA ethnic groups may help guide asthma screening and prevention measures and offer new insights into asthma pathogenesis.

Geographic variation in disease burden among patients with severe persistent asthma in the United States.

BACKGROUND: In the United States, a few studies have evaluated geographic variation of severe asthma at the subnational level. OBJECTIVE: To assess state-level geographic variation in the prevalence and characteristics of severe persistent asthma in the United States. METHODS: Patients aged above or equal to 12 years with severe persistent asthma were identified using nationally representative data from IQVIA open-source Medical/Pharmacy Claims and PharMetrics Plus databases (January 2019-December 2020). The index date was defined as the patient's earliest qualifying date for a severe asthma diagnosis. Baseline characteristics were measured during the 12-month pre-index period. Outcomes including exacerbation occurrence, asthma control, and medication use were measured during the 12-month post-index period and compared across states using census-level projections. RESULTS: A total of 2,092,799 patients with asthma were identified; 496,750 (23.7%) met criteria for severe persistent asthma and all inclusion criteria. Mean age was 50.5 years; 68.4% were females. The prevalence of severe persistent asthma varied across states, ranging from 19.6% (New Mexico) to 31.9% (Alaska). Among patients with severe persistent asthma, 40.9% had more than or equal to 1 exacerbation, ranging from 34.2% (Vermont) to 45.6% (Louisiana); 21.1% had uncontrolled disease, ranging from 16.5% (Vermont) to 24.0% (Arizona). Among patients with exacerbations, 13.7% had exacerbation-related emergency department visits or hospitalizations, ranging from 7.0% (North Carolina) to 17.7% (Nevada). Among patients with severe uncontrolled asthma, 15.6% used biologics post-index, ranging from 2.2% (Hawaii) to 27.9% (Mississippi). CONCLUSION: There is significant variability in severe persistent asthma prevalence and disease burden across US states. Reasons for geographic variation may include differences in socioeconomic/environmental factors or asthma management.

Association of respiratory virus types with clinical features in bronchiolitis: Implications for virus testing strategies. A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features. METHODS: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated. RESULTS: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined. CONCLUSIONS: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.

Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO programme.

OBJECTIVE: n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake. DESIGN: Pooled pregnancy cohort studies. SETTING: Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. PARTICIPANTS: A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. RESULTS: Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 v. <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v. healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v. never). CONCLUSIONS: One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n-3 supplement use was uncommon, even among those who did not consume fish.

Association between EMS Workforce Density and Population Health Outcomes in the U.S.

BACKGROUND: The prehospital care provided by emergency medical services (EMS) personnel is a critical component of the public health, public safety, and health care systems in the U.S.; however, the population-level value of EMS care is often overlooked. No studies have examined how the density of EMS personnel relates to population-level health outcomes. Our objectives were to examine the geographic distribution and density of EMS personnel in the U.S.; and quantify the association between EMS personnel density and population-level health outcomes. METHODS: We conducted a cross-sectional evaluation of county-level EMS personnel density using estimates from the National Registry of Emergency Medical Technicians in nine states that require continuous national certification (Alabama, Louisiana, Massachusetts, Minnesota, New Hampshire, North Dakota, South Carolina, Vermont, and Washington, D.C.). Outcomes of interest included life expectancy, all-cause mortality, and cardiac arrest mortality. We used quantile regression models to examine the association between a 10-person increase in EMS personnel density and each outcome at the 10th, 50th (median), and 90th percentiles, controlling for population characteristics and area health resources. RESULTS: There were 356 counties included, with a mean EMS density of 223 EMS personnel per 100,000 population. Density was higher in rural compared to urban counties (247 versus 186 per 100,000 population; p = 0.001). In unadjusted models, there was a significant association between increase in EMS personnel density and an increase in life expectancy at each examined percentile (e.g., 50th percentile, increase of 52.9 days; 95% CI 40.2, 65.5; p < 0.001), decrease in all-cause mortality at each examined percentile, and decrease in cardiac arrest mortality at the 50th and 90th percentiles. These associations were not statistically significant in the adjusted models. CONCLUSIONS: EMS personnel density differs between urban and rural areas, with higher density per population in rural areas. There were no statistically significant associations between EMS density and population-level health outcomes after controlling for population characteristics and other health resources. The best approach to quantifying the community-level value that EMS care may or may not provide remains unclear.

Emergency Medical Services Management of Bronchospasm in the United States: A Cross-Sectional Analysis and Nationwide Quality Assessment.

Background/Objective: Bronchospasm, caused by asthma and other related conditions, is a significant cause of morbidity and mortality commonly managed by emergency medical services (EMS). We aimed to evaluate the quality of prehospital management of bronchospasm by EMS in the US.Methods: The National EMS Information System Public Release Research dataset, a nationwide convenience sample of prehospital patient care report data from 2018 to 2019, was used to capture 9-1-1 activations where patients aged ≥2 years were treated and transported by EMS for suspected bronchospasm. First, we described the extent to which EMS care met eight quality measures identified from available statewide EMS protocols, existing quality measures, and national guidelines. Second, we quantified the extent of risk-standardized agency-level variation in administration of inhaled beta agonists and systemic corticosteroids using logistic regression models, accounting for patient characteristics, severity, and clustering by agencies. Third, we compared rates of completed prehospital interventions between pediatric (age <18 years) versus adult patients using two-sample t-tests.Results: A total of 1,336,988 EMS encounters for suspected bronchospasm met inclusion criteria. Median age of patients was 66 years, with only 4% pediatric; 55% were female. Advanced life support (ALS) units managed 94% of suspected bronchospasm. Respiratory rate (98%) and pulse oximetry (96%) were documented in nearly all cases. Supplemental oxygen was administered to hypoxic patients by 65% of basic life support (BLS) and 73% of ALS units. BLS administered inhaled beta-agonist therapy less than half the time (48%), compared to 77% by ALS. ALS administered inhaled anticholinergic therapy in 38% of cases, and systemic corticosteroids in 19% of cases. Pediatric patients were significantly less likely to receive supplemental oxygen when hypoxic, inhaled beta-agonists, inhaled anticholinergics, or systemic corticosteroids.Conclusions: We found important gaps in recent EMS practice for prehospital care of suspected bronchospasm. We highlight three targets for improvement: inhaled beta-agonist administration by BLS, systemic corticosteroid administration by ALS, and increased interventions for pediatric patients. These findings indicate important areas for research, protocol modification, and quality improvement efforts to improve EMS management of bronchospasm.

Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

BACKGROUND: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. OBJECTIVES: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. METHODS: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). RESULTS: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. CONCLUSIONS: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

A Comparison of State-Specific Pediatric Emergency Medical Facility Recognition Programs, 2020.

OBJECTIVES: Prior research suggests that the presence of state-specific pediatric emergency medical facility recognition programs (PFRPs) is associated with high emergency department (ED) pediatric readiness. The PFRPs aim to improve the quality of pediatric emergency care, but individual state programs differ. We aimed to describe the variation in PFRP characteristics and verification requirements and to describe the availability of pediatric emergency care coordinators (PECCs) in states with PFRPs. METHODS: In mid-2020, we collected information about each PFRP from 3 sources: the state Emergency Medical Services for Children (EMSC) website, the EMSC Innovation and Improvement Center website, or via communication with the state's EMSC program manager. For each state with a PFRP, we documented program characteristics, including program start date, number of tiers, whether participation was required/optional, and requirements for verification. RESULTS: Overall, we identified 17 states with active PFRPs. Five states had only 1 tier or level of recognition whereas the others had multiple. All programs did require presence of a PECC for verification. However, some PRFPs with multiple verification tiers did not require presence of a PECC to achieve each level of verification. In states with PFRPs, EDs with higher total visit volumes, a separate pediatric ED area, located in the Northeast, and earlier program start date were all more likely to have a PECC. CONCLUSIONS: There is variation in state PFRPs, although all prioritize the presence of a PECC. We encourage further research on the effect of different aspects of PFRPs on patient outcomes.

Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

Emergency Department and Health Care System Factors Associated with Telehealth Innovation During the COVID-19 Pandemic.

Objective: Telehealth capacity may be an important component of pandemic response infrastructure. We aimed to examine changes in the telehealth use by the US emergency departments (EDs) during COVID-19, and to determine whether existing telehealth infrastructure or increased system integration were associated with increased likelihood of use. Methods: We analyzed 2016-2020 National ED Inventory (NEDI)-USA data, including ED characteristics and nature of telehealth use for all US EDs. American Hospital Association data characterized EDs' system integration. An ordinary least-squares regression model obtained one-step-ahead forecast of the expected proportion of EDs using telehealth in 2020 based on growth observed from 2016 to 2019. Among EDs without telehealth in 2019, we used logistic regression models to examine whether system membership or existing telehealth infrastructure were associated with odds of innovation in telehealth use in 2020, accounting for ED characteristics. Results: Of 4,038 EDs responding to telehealth questions in 2019 and 2020 (73% response rate), 3,015 used telehealth in 2020. Telehealth use by US EDs increased more than expected in 2020 (2016: 58%, 2017: 61%, 2018: 65%, 2019: 67%, 2020: 74%, greater than predicted 71%, p = 0.004). Existing telehealth infrastructure was associated with increased telehealth innovation (OR = 1.88, 95% CI: 1.49-2.36), whereas hospital system membership was not (odds ratio [OR] = 1.00, 95% confidence interval [CI]: 0.80-1.25). Conclusions: Telehealth use by US EDs in 2020 grew more than expected and preexisting telehealth infrastructure was associated with increased innovation in its use. Preparation for future pandemic responses may benefit from considering strategies to invest in local infrastructure to facilitate technology adoption and innovation.

Respiratory Virus-Specific Nasopharyngeal Lipidome Signatures and Severity in Infants With Bronchiolitis: A Prospective Multicenter Study.

BACKGROUND: In infant bronchiolitis, recent evidence indicates that respiratory viruses (eg, respiratory syncytial virus [RSV], rhinovirus [RV]) contribute to the heterogeneity of disease severity. Of the potential pathobiological molecules, lipids serve as signaling molecules in airway inflammation. However, little is known about the role of the airway lipidome in between-virus heterogeneity and disease severity. METHODS: In this multicenter prospective study of 800 infants hospitalized for RSV or RV bronchiolitis, we analyzed nasopharyngeal lipidome data. We examined discriminatory lipids between RSV and RV infection and the association of the discriminatory lipids with bronchiolitis severity, defined by positive pressure ventilation (PPV) use. RESULTS: We identified 30 discriminatory nasopharyngeal lipid species and 8 fatty acids between RSV and RV infection. In the multivariable models adjusting for patient-level confounders, 8 lipid species-for example, phosphatidylcholine (18:2/18:2) (adjusted odds ratio [aOR], 0.23 [95% confidence interval {CI}, .11-.44]; false discovery rate [FDR] = 0.0004) and dihydroceramide (16:0) (aOR, 2.17 [95% CI, 1.12-3.96]; FDR = 0.04)-were significantly associated with the risk of PPV use. Additionally, 6 fatty acids-for example, eicosapentaenoic acid (aOR, 0.27 [95% CI, .11-.57]; FDR = 0.01)-were also significantly associated with the risk of PPV use. CONCLUSIONS: In infants hospitalized for bronchiolitis, the nasopharyngeal lipidome plays an important role in the pathophysiology of between-virus heterogeneity and disease severity.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study.

BACKGROUND: Severe bronchiolitis (i.e. bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma. METHODS: In a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines. RESULTS: In 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development (e.g. hsa-miR-29a-3p; false discovery rate (FDR) <0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction <0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR <0.05), e.g. infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells (e.g. T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g. hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR <0.05), e.g. toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data. CONCLUSION: In a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization.

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV-A or RV-C types using log-linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV-A versus RV-C nAb responses. Our models identified limited reciprocal cross-neutralizing relationships for RV-A (A12-A75, A12-A78, A20-A78, and A75-A78) and only one for RV-C (C2-C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV-C2. Mixed-effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV-A and RV-C illnesses induced nAb responses of similar duration. These results indicate that both RV-A and RV-C nAb responses have only modest cross-reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV-C species may include even fewer cross-neutralizing types than RV-A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.