Publications by authors named "Stephen J Teach"

139 Publications

Social Determinants of Health and At-Risk Rates for Pediatric Asthma Morbidity.

Pediatrics 2022 Aug;150(2)

Department of Pediatrics, Children's National Hospital, Washington, District of Columbia.

Background And Objectives: Compared with population-based rates, at-risk rates (ARRs) account for underlying variations of asthma prevalence. When applied with geospatial analysis, ARRs may facilitate more accurate evaluations of the contribution of place-based social determinants of health (SDOH) to pediatric asthma morbidity. Our objectives were to calculate ARRs for pediatric asthma-related emergency department (ED) encounters and hospitalizations by census-tract in Washington, the District of Columbia (DC) and evaluate their associations with SDOH.

Methods: This population-based, cross-sectional study identified children with asthma, 2 to 17 years old, living in DC, and included in the DC Pediatric Asthma Registry from January 2018 to December 2019. ED encounter and hospitalization ARRs (outcomes) were calculated for each DC census-tract. Five census-tract variables (exposures) were selected by using the Healthy People 2030 SDOH framework: educational attainment, vacant housing, violent crime, limited English proficiency, and families living in poverty.

Results: During the study period, 4321 children had 7515 ED encounters; 1182 children had 1588 hospitalizations. ARRs varied 10-fold across census-tracts for both ED encounters (64-728 per 1000 children with asthma) and hospitalizations (20-240 per 1000 children with asthma). In adjusted analyses, decreased educational attainment was significantly associated with ARRs for ED encounters (estimate 12.1, 95% confidence interval [CI] 8.4 to 15.8, P <.001) and hospitalizations (estimate 1.2, 95% CI 0.2 to 2.2, P = .016). Violent crime was significantly associated with ARRs for ED encounters (estimate 35.3, 95% CI 10.2 to 60.4, P = .006).

Conclusion: Place-based interventions addressing SDOH may be an opportunity to reduce asthma morbidity among children with asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2021-055570DOI Listing
August 2022

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.

medRxiv 2022 Jul 10. Epub 2022 Jul 10.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2022.07.09.22277457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298141PMC
July 2022

Total immunoglobulin E in infant bronchiolitis and risk of developing asthma.

J Allergy Clin Immunol Pract 2022 Jul 5. Epub 2022 Jul 5.

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2022.06.043DOI Listing
July 2022

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study.

J Allergy Clin Immunol 2022 Aug 1;150(2):302-311. Epub 2022 Jun 1.

University of Wisconsin School of Medicine and Public Health, Madison, Wisc.

Background: Whether children and people with asthma and allergic diseases are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection is unknown.

Objective: Our aims were to determine the incidence of SARS-CoV-2 infection in households with children and to also determine whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission.

Methods: For 6 months, biweekly nasal swabs and weekly surveys were conducted within 1394 households (N = 4142 participants) to identify incident SARS-CoV-2 infections from May 2020 to February 2021, which was the pandemic period largely before a vaccine and before the emergence of SARS-CoV-2 variants. Participant and household infection and household transmission probabilities were calculated by using time-to-event analyses, and factors associated with infection and transmission risk were determined by using regression analyses.

Results: In all, 147 households (261 participants) tested positive for SARS-CoV-2. The household SARS-CoV-2 infection probability was 25.8%; the participant infection probability was similar for children (14.0% [95% CI = 8.0%-19.6%]), teenagers (12.1% [95% CI = 8.2%-15.9%]), and adults (14.0% [95% CI = 9.5%-18.4%]). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (adjusted hazard ratio [aHR] = 1.04 [95% CI = 0.73-1.46]), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR = 0.50 [95% CI = 0.32-0.81]); higher body mass index was associated with increased infection risk (aHR per 10-point increase = 1.09 [95% CI = 1.03-1.15]). The household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (adjusted odds ratio = 0.43 [95% CI = 0.19-0.96]; P = .04).

Conclusion: Asthma does not increase the risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, whereas body mass index is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for preventing infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2022.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9155183PMC
August 2022

Hospitalization to emergency department visit ratio for pediatric asthma: A population-based study.

J Allergy Clin Immunol Pract 2022 Aug 11;10(8):2184-2186.e2. Epub 2022 May 11.

Children's National Hospital, Washington, DC; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2022.04.038DOI Listing
August 2022

Effect of the coronavirus disease 2019 pandemic on morbidity among children hospitalized for an asthma exacerbation.

Ann Allergy Asthma Immunol 2022 08 8;129(2):194-198.e1. Epub 2022 Apr 8.

Department of Pediatrics, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address:

Background: Pediatric asthma exacerbations account for substantial morbidity, including emergency department (ED) visits and hospitalizations. Although the coronavirus disease 2019 (COVID-19) pandemic was associated with a decrease in pediatric asthma ED visits and hospitalizations, there is limited information on the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic.

Objective: To investigate the clinical characteristics of children hospitalized with an asthma exacerbation during the pandemic as compared with those hospitalized during the same months in the year prior.

Methods: A retrospective case-control study was conducted at the Children's National Hospital, Washington, DC, comparing demographic and clinical characteristics of all children, 2 to 18 years old, hospitalized for an asthma exacerbation between April to September 2020 (cases) and April to September 2019 (controls).

Results: We identified 50 cases and 243 controls. Cases were significantly older than controls (9.8 ± 4.3 years vs 6.7 ± 3.8 years; P < .001), had significantly less eczema (16% vs 32.1%; P = .02) and food allergies (6% vs 18.5%; P = .03), and were more noncompliant with controller medications (46% vs 24.7%; P = .002) than controls. Magnesium sulfate was more frequently administered in the ED to the cases than to the controls (84% vs 63%; P = .004). Its use was associated with older age, African American race, and Hispanic ethnicity, but was independent of comorbid conditions.

Conclusion: Patients hospitalized for asthma during the COVID-19 pandemic were older and have less atopy than those hospitalized prepandemic. A larger proportion received magnesium sulfate in the ED, suggesting patients had with more severe asthma presentation during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anai.2022.03.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9049585PMC
August 2022

Stressful life events, caregiver depressive symptoms, and child asthma symptom-free days: a longitudinal analysis.

J Asthma 2022 Apr 13:1-8. Epub 2022 Apr 13.

Center for Translational Research, Children's National Research Institute, Washington, DC, USA.

Objective: To examine relationships among stressful life events (SLE), caregiver depression, and asthma symptom free days (SFDs) in publicly insured Black children aged 4-12 years with persistent asthma.

Methods: Secondary analysis of longitudinal data from a clinical trial assessing the efficacy of a six-month parental stress management intervention. Using repeated measures Poisson regression, we constructed four models of SLE (Rochester Youth Development Stressful Life Events scale-Parent Items), caregiver depression (Center for Epidemiologic Studies Depression scale ≥ 11), and child asthma symptom-free days (SFDs) in the prior 14 days.

Results: There was no association between SLE and child SFDs, but there was for caregiver depression (Incidence Rate Ratio [IRR]: 0.904; 95% CI 0.86-0.95). The interaction between SLE and caregiver depression was not significant. A specific SLE (recent serious family accident or illness) predicted fewer child SFDs (IRR: 0.91, 95% CI: 0.85-0.98). In the interaction model between caregiver depression and recent accident/illness, caregiver depression was associated with fewer child SFDs (IRR: 0.95, 95% CI: 0.91-0.99) as was the interaction between caregiver depression and recent accident/illness (IRR: 0.77, 95% CI 0.66-0.91); but the relationship between recent accident/illness and child SFDs was not (IRR: 1.00, 95% CI, 0.92-1.09), meaning accident/illness was only associated with fewer child SFDs among depressed caregivers.

Conclusions: In a sample of publicly insured Black children with persistent asthma, caregiver depression was negatively associated with child SFDs while overall SLE were not. A recent family accident or illness was negatively associated with child SFDs only when the caregiver was depressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2022.2062674DOI Listing
April 2022

Early Outcomes of a New NIH Program to Support Research in Residency.

Acad Med 2022 Mar 1. Epub 2022 Mar 1.

M.P. Rapoza is associate professor, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. A. McElvaine is director, Office of Physician-Scientist Development, Duke University School of Medicine, Durham, North Carolina. M.B. Conroy is professor, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah. K. Okuyemi is professor, Department of Family and Preventative Medicine, University of Utah School of Medicine, Salt Lake City, Utah. N. Rouphael is associate professor, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. S.J. Teach is chair, Department of Pediatrics, Children's National Research Institute, Washington, DC. M. Widlansky is professor of medicine and pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin. C. Williams is professor, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. S.R. Permar is chair, Department of Pediatrics, Weill Cornell Medicine, New York, New York.

The work of physician-investigators has historically led to key discoveries and developments in modern medicine, but recent decades have seen significant declines in the number of U.S. physician-investigators. One of the barriers to physicians participating in research is the lack of mentored research opportunities during clinical training, especially during residency training. In response to this identified barrier and to expand the physician-investigator workforce, the National Institutes of Health initiated the R38 program, known as Stimulating Access to Research in Residency, to support mentored research opportunities for residents. This article reports on the early outcomes of the recipients of the initial round of R38 awards, granted in 2018. Early positive outcomes include increases in the reported likelihood of resident-investigators pursuing physician-investigator careers, greater reported clarity in resident-investigators' research directions, the commitment of additional institutional resources to support the R38-awarded programs, and the approval of resident-investigators as having met training requirements for certification by multiple medical boards.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0000000000004643DOI Listing
March 2022

Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations.

J Allergy Clin Immunol 2022 Jul 8;150(1):204-213. Epub 2022 Feb 8.

Department of Medicine, University of California, San Francisco, Calif. Electronic address:

Background: Seasonal variation in respiratory illnesses and exacerbations in pediatric populations with asthma is well described, though whether upper airway microbes play season-specific roles in these events is unknown.

Objective: We hypothesized that nasal microbiota composition is seasonally dynamic and that discrete microbe-host interactions modify risk of asthma exacerbation in a season-specific manner.

Methods: Repeated nasal samples from children with exacerbation-prone asthma collected during periods of respiratory health (baseline; n = 181 samples) or first captured respiratory illness (n = 97) across all seasons, underwent bacterial (16S ribosomal RNA gene) and fungal (internal transcribed spacer region 2) biomarker sequencing. Virus detection was performed by multiplex PCR. Paired nasal transcriptome data were examined for seasonal dynamics and integrative analyses.

Results: Upper airway bacterial and fungal microbiota and rhinovirus detection exhibited significant seasonal dynamics. In seasonally adjusted analysis, variation in both baseline and respiratory illness microbiota related to subsequent exacerbation. Specifically, in the fall, when respiratory illness and exacerbation events were most frequent, several Moraxella and Haemophilus members were enriched both in virus-positive respiratory illnesses and those that progressed to exacerbations. The abundance of 2 discrete bacterial networks, characteristically comprising either Streptococcus or Staphylococcus, exhibited opposing interactions with an exacerbation-associated SMAD3 nasal epithelial transcriptional module to significantly increase the odds of subsequent exacerbation (odds ratio = 14.7, 95% confidence interval = 1.50-144, P = .02; odds ratio = 39.17, 95% confidence interval = 2.44-626, P = .008, respectively).

Conclusions: Upper airway microbiomes covary with season and with seasonal trends in respiratory illnesses and asthma exacerbations. Seasonally adjusted analyses reveal specific bacteria-host interactions that significantly increase risk of asthma exacerbation in these children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2022.01.020DOI Listing
July 2022

SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection.

Front Immunol 2021 18;12:793197. Epub 2022 Jan 18.

Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.

Background: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection.

Methods: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay.

Findings: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults.

Interpretation: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.793197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803660PMC
February 2022

Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.

Clin Transl Allergy 2021 Oct 13;11(8):e12073. Epub 2021 Oct 13.

Division of Vaccine Discovery La Jolla Institute for Immunology La Jolla California USA.

Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining.

Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract.

Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clt2.12073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514843PMC
October 2021

Increasing Pediatric Residency Class Diversity to Improve Patient Outcomes and Address Structural Racism.

Acad Med 2022 Jun 19;97(6):850-854. Epub 2021 Oct 19.

A. Barber is residency program director, Children's National Hospital, and associate professor, Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC.

Problem: The racial and ethnic makeup of physicians in the United States does not reflect that of the communities they serve. Addressing this disparity may improve patient outcomes and combat structural racism.

Approach: Starting in 2014, the pediatric residency program at Children's National Hospital deliberately worked to assemble residency classes with racial and ethnic diversity that was similar to that of the Washington, DC, community it served. This work consisted of 3 initiatives: the Minority Senior Scholarship Program (MSSP), a pipeline program for rising fourth-year underrepresented in medicine (UIM) medical students to expose them to careers in academic pediatrics; an enhanced applicant recruitment process for UIM applicants; and mechanisms like a diversity dinner series for UIM residents to find the support they need to succeed.

Outcomes: Since its inception in 2015, 73 participants have completed the MSSP, with 26% (19/73) going on to match at Children's National Hospital. An additional 12 participants are completing the program during the 2022 Match cycle. The MSSP has also increased participants' self-reported interest in pursuing a career in academic pediatrics, from 70% (14/20) before participation to 95% (19/20) after participation. In addition, the enhanced recruitment efforts have proven fruitful. The percentage of UIM interns at Children's National Hospital has increased from 5% (2/40) in 2014 to 51% (21/41) in 2021.

Next Steps: The dimensions of diversity included in these initiatives will be expanded to include individuals from other marginalized populations, such as certain individuals of Southeast Asian descent, those who identify as LGBTQ+, and those with disabilities. An antiracism initiative has also been implemented in the residency program in collaboration with the hospital and partner medical schools.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0000000000004468DOI Listing
June 2022

Association of mold levels in urban children's homes with difficult-to-control asthma.

J Allergy Clin Immunol 2022 04 2;149(4):1481-1485. Epub 2021 Oct 2.

Cincinnati Children's Hospital, Cincinnati, Ohio.

Background: Mold sensitization and exposure are associated with asthma severity, but the specific species that contribute to difficult-to-control (DTC) asthma are unknown.

Objective: We sought to determine the association between overall and specific mold levels in the homes of urban children and DTC asthma.

Methods: The Asthma Phenotypes in the Inner-City study recruited participants, aged 6 to 17 years, from 8 US cities and classified each participant as having either DTC asthma or easy-to-control (ETC) asthma on the basis of treatment step level. Dust samples had been collected in each participant's home (n = 485), and any dust remaining (n = 265 samples), after other analyses, was frozen at -20C. The dust samples (n = 265) were analyzed using quantitative PCR to determine the concentrations of the 36 molds in the Environmental Relative Moldiness Index. Logistic regression was performed to discriminate specific mold content of dust from homes of children with DTC versus ETC asthma.

Results: Frozen-dust samples were available from 54% of homes of children with DTC (139 of 253) and ETC asthma (126 of 232). Only the average concentration of the mold Mucor was significantly (P < .001) greater in homes of children with DTC asthma. In homes with window air-conditioning units, the Mucor concentration contributed about a 22% increase (1.6 odds ratio; 95% CI, 1.2-2.2) in the ability to discriminate between cases of DTC and ETC asthma.

Conclusions: Mucor levels in the homes of urban youth were a predictor of DTC asthma, and these higher Mucor levels were more likely in homes with a window air-conditioner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.07.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975947PMC
April 2022

Association between pediatric asthma and positive tests for SARS-CoV-2 in the District of Columbia.

J Allergy Clin Immunol Pract 2021 09 12;9(9):3490-3493. Epub 2021 Jul 12.

Center for Translational Research, Children's National Research Institute, Washington, DC; Division of Emergency Medicine, Children's National Hospital, Washington, DC. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274272PMC
September 2021

Inducible expression quantitative trait locus analysis of the MUC5AC gene in asthma in urban populations of children.

J Allergy Clin Immunol 2021 12 18;148(6):1505-1514. Epub 2021 May 18.

University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Mucus plugging can worsen asthma control, lead to reduced lung function and fatal exacerbations. MUC5AC is the secretory mucin implicated in mucus plugging, and MUC5AC gene expression has been associated with development of airway obstruction and asthma exacerbations in urban children with asthma. However, the genetic determinants of MUC5AC expression are not established.

Objectives: This study sought to assess single-nucleotide polymorphisms (SNPs) that influence MUC5AC expression and relate to pulmonary functions in childhood asthma.

Methods: This study used RNA-sequencing data from upper airway samples and performed cis-expression quantitative trait loci (eQTL) and allele-specific expression analyses in 2 cohorts of predominantly Black and Hispanic urban children, a high asthma-risk birth cohort, and an exacerbation-prone asthma cohort. Inducible MUC5AC eQTLs were further investigated during incipient asthma exacerbations. Significant eQTLs SNPs were tested for associations with lung function measurements and their functional consequences were investigated in DNA regulatory databases.

Results: Two independent groups of SNPs in the MUC5AC gene that were significantly associated with MUC5AC expression were identified. Moreover, these SNPs showed stronger eQTL associations with MUC5AC expression during asthma exacerbations, which is consistent with inducible expression. SNPs in 1 group also showed significant association with decreased pulmonary functions. These SNPs included multiple EGR1 transcription factor binding sites, suggesting a mechanism of effect.

Conclusions: These findings demonstrate the applicability of organ-specific RNA-sequencing data to determine genetic factors contributing to a key disease pathway. Specifically, they suggest important genetic variations that may underlie propensity to mucus plugging in asthma and could be important in targeted asthma phenotyping and disease management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.04.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599524PMC
December 2021

The indirect effects of COVID-19 on pediatric research.

Pediatr Res 2021 08 7;90(2):246-247. Epub 2021 May 7.

Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-021-01563-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102840PMC
August 2021

Creation and validation of a citywide pediatric asthma registry for the District of Columbia.

J Asthma 2022 05 22;59(5):901-909. Epub 2021 Mar 22.

District of Columbia Department of Health, Washington, DC, USA.

Objective: To create and validate a citywide pediatric Asthma Registry to improve the care and outcomes of children and adolescents in Washington, DC through data-driven quality improvement (QI).

Methods: All available electronic health record data from inpatient and outpatient domains of Children's National Hospital were aggregated from an existing enterprise data warehouse. Inclusion criteria included asthma relevant ICD-10 codes over the prior 24 months. Available Asthma Registry measures include patient demographics, ambulatory visits, hospital admissions, persistent asthma diagnoses, and prescription of controller medications. Data capture was validated using US Census data and current asthma prevalence estimate of the Behavioral Risk Factor Surveillance System (BRFSS).

Results: The registry identified 15,991 DC children and adolescents with asthma aged 0-17 years, inclusive, at the end of 2020. This was 14.2% higher than the estimate of 14,001 children derived from BRFSS. Characteristics of those in the registry included: mean age of 9.5 (1.4) years, 57.9% male, 72.3% Black, and 66.7% publicly insured. Over the prior 24 months, 30.3% had ≥1 emergency department visit, and 10.5% had ≥1 hospital admission. Controller medications were prescribed for 59.6% of children with persistent asthma. Rates varied by sampled primary care practice sites.

Conclusions: A population-level pediatric asthma registry captures more children and adolescents with asthma in DC then a BRFSS-derived estimate, and provides city-wide measures of asthma-related utilization. The registry allows for stratification by primary care practice locations and asthma characteristics, supporting the design, implementation, and evaluation of QI projects at the practice, health system, and population levels.

Supplemental data for this article can be accessed at publisher's website.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2021.1895213DOI Listing
May 2022

Pediatric asthma exacerbations during the COVID-19 pandemic: Absence of the typical fall seasonal spike in Washington, DC.

J Allergy Clin Immunol Pract 2021 05 16;9(5):2073-2076. Epub 2021 Feb 16.

Division of Emergency Medicine, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884913PMC
May 2021

Development of nasal allergen challenge with cockroach in children with asthma.

Pediatr Allergy Immunol 2021 07 20;32(5):971-979. Epub 2021 Mar 20.

Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.

Background: Nasal allergen challenge (NAC) could be a means to assess indication and/or an outcome of allergen-specific therapies, particularly for perennial allergens. NACs are not commonly conducted in children with asthma, and cockroach NACs are not well established. This study's objective was to identify a range of German cockroach extract doses that induce nasal symptoms and to assess the safety of cockroach NAC in children with asthma.

Methods: Ten adults (18-37 years) followed by 25 children (8-14 years) with well-controlled, persistent asthma and cockroach sensitization underwent NAC with diluent followed by up to 8 escalating doses of cockroach extract (0.00381-11.9 µg/mL Bla g 1). NAC outcome was determined by Total Nasal Symptom Score (TNSS) and/or sneeze score. Cockroach allergen-induced T-cell activation and IL-5 production were measured in peripheral blood mononuclear cells.

Results: 67% (6/9) of adults and 68% (17/25) of children had a positive NAC at a median response dose of 0.120 µg/mL [IQR 0.0380-0.379 µg/mL] of Bla g 1. Additionally, three children responded to diluent alone and did not receive any cockroach extract. Overall, 32% (11/34) were positive with sneezes alone, 15% (5/34) with TNSS alone, and 21% (7/34) with both criteria. At baseline, NAC responders had higher cockroach-specific IgE (P = .03), lower cockroach-specific IgG/IgE ratios (children, P = .002), and increased cockroach-specific IL-5-producing T lymphocytes (P = .045). The NAC was well tolerated.

Conclusion: We report the methodology of NAC development for children with persistent asthma and cockroach sensitization. This NAC could be considered a tool to confirm clinically relevant sensitization and to assess responses in therapeutic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503840PMC
July 2021

Management of Asthma Exacerbations in the Emergency Department.

J Allergy Clin Immunol Pract 2021 07 31;9(7):2599-2610. Epub 2020 Dec 31.

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

Asthma exacerbations occur across a wide spectrum of chronic severity; they contribute to millions of emergency department (ED) visits in both children and adults every year. Management of asthma exacerbations is an important part of the continuum of asthma care. The best strategy for ED management of an asthma exacerbation is early recognition and intervention, continuous monitoring, appropriate disposition, and, once improved, multifaceted transitional care that optimizes subacute and chronic asthma management after ED discharge. This article concisely reviews ED evaluation, treatment, disposition, and postdischarge care for patients with asthma exacerbations, based on high-quality evidence (eg, systematic reviews from the Cochrane Collaboration) and current international guidelines (eg, the National Asthma Education and Prevention Program Expert Panel Report 3, Global Initiative for Asthma, and Australian guidelines). Special populations (young children, pregnant women, and the elderly) also are addressed. Despite advances in asthma science, there remain many important evidence gaps in managing ED patients with asthma exacerbation. This article summarizes several of these controversial areas and challenges that merit further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.12.037DOI Listing
July 2021

2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group.

J Allergy Clin Immunol 2020 12;146(6):1217-1270

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda.

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders:A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality's (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924476PMC
December 2020

Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation.

Contemp Clin Trials 2021 01 24;100:106228. Epub 2020 Nov 24.

Boston Children's Hospital, Division of Allergy and Immunology, United States of America; Harvard Medical School, Boston, MA, United States of America.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cct.2020.106228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887056PMC
January 2021

Serum Soluble Receptor for Advanced Glycation End Products in Infants With Bronchiolitis: Associations With Acute Severity and Recurrent Wheeze.

Clin Infect Dis 2021 11;73(9):e2665-e2672

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze.

Methods: A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze.

Results: In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30).

Conclusions: Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563181PMC
November 2021

Outcomes from a pilot patient-centered hospital-to-home transition program for children hospitalized with asthma.

J Asthma 2021 10 4;58(10):1384-1394. Epub 2020 Aug 4.

Center for Translational Research, Children's National Research Institute, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Objective: To evaluate a multi-component hospital-to-home (H2H) transition program for children hospitalized with an asthma exacerbation.

Methods: A pilot prospective randomized clinical trial of guideline-based asthma care with and without a patient-centered multi-component H2H program among children enrolled in K-8 grade on Medicaid hospitalized for an asthma exacerbation. H2H program includes 5 components: medications in-hand at discharge, school-based asthma therapy (SBAT) for controller medications, referral for home trigger assessments, communication with the primary care provider (PCP), and patient navigator support. Primary outcomes included feasibility and acceptability. Secondary outcomes included healthcare utilization, asthma morbidity, and caregiver quality of life.

Results: A total of 32 children were enrolled and randomized. Feasibility outcomes in the intervention group included: medications in-hand at discharge (100%); SBAT for controller medication initiated (100%); home visit referrals made (100%) and home visits completed within 4 weeks of discharge (44%); PCP communication (100%); patient navigator communication at 3 days (81.3%) and 14 days (46.7%). Acceptability outcomes in the intervention group included: 87.5% of families continued SBAT, and 87.5% of families reported it was extremely helpful to have the home visit referral. Adjusting for baseline differences in age, asthma severity and control, there was no significant difference in healthcare utilization outcomes.

Conclusion: These pilot data suggest that comprehensive care coordination initiated during the inpatient stay is feasible and acceptable. A larger trial is justified to determine if the intervention may reduce healthcare utilization for urban, minority children with asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2020.1795877DOI Listing
October 2021

Machine learning-based prediction of acute severity in infants hospitalized for bronchiolitis: a multicenter prospective study.

Sci Rep 2020 07 3;10(1):10979. Epub 2020 Jul 3.

Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, 125 Nashua Street, Suite 920, Boston, MA, 02114-1101, USA.

We aimed to develop machine learning models to accurately predict bronchiolitis severity, and to compare their predictive performance with a conventional scoring (reference) model. In a 17-center prospective study of infants (aged < 1 year) hospitalized for bronchiolitis, by using routinely-available pre-hospitalization data as predictors, we developed four machine learning models: Lasso regression, elastic net regression, random forest, and gradient boosted decision tree. We compared their predictive performance-e.g., area-under-the-curve (AUC), sensitivity, specificity, and net benefit (decision curves)-using a cross-validation method, with that of the reference model. The outcomes were positive pressure ventilation use and intensive treatment (admission to intensive care unit and/or positive pressure ventilation use). Of 1,016 infants, 5.4% underwent positive pressure ventilation and 16.0% had intensive treatment. For the positive pressure ventilation outcome, machine learning models outperformed reference model (e.g., AUC 0.88 [95% CI 0.84-0.93] in gradient boosted decision tree vs 0.62 [95% CI 0.53-0.70] in reference model), with higher sensitivity (0.89 [95% CI 0.80-0.96] vs. 0.62 [95% CI 0.49-0.75]) and specificity (0.77 [95% CI 0.75-0.80] vs. 0.57 [95% CI 0.54-0.60]). The machine learning models also achieved a greater net benefit over ranges of clinical thresholds. Machine learning models consistently demonstrated a superior ability to predict acute severity and achieved greater net benefit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-67629-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335203PMC
July 2020

Pathways to Improve Pediatric Asthma Care: A Multisite, National Study of Emergency Department Asthma Pathway Implementation.

J Pediatr 2020 08 11;223:100-107.e2. Epub 2020 May 11.

Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.

Objective: To determine the effects of pediatric asthma pathway implementation in a diverse, national sample of emergency departments (EDs).

Study Design: In this quality improvement study, a national sample of EDs were provided pathways to tailor to local needs. Implementation strategies included local champions, external facilitators/mentors, educational seminars, and audit and feedback. Outcomes included systemic corticosteroid administration within 60 minutes (primary), assessment of severity at ED triage, chest radiograph use, hospital admission or transfer for higher level of care, and ED length of stay (balancing). Each month, EDs reviewed all charts (to a maximum of 20) of children ages 2-17 years with a primary diagnosis of asthma. Analyses were done using multilevel regression models with an interrupted time-series approach, adjusting for patient characteristics.

Results: We enrolled 83 EDs (37 in children's hospitals, 46 in community hospitals) and 61 (73%) completed the study (n = 22 963 visits). Pathway implementation was associated with significantly increased odds of systemic corticosteroid administration within 60 minutes of arrival (aOR, 1.26; 95% CI, 1.02-1.55), increased odds of severity assessment at triage (aOR, 1.88; 95% CI, 1.22-2.90), and decreased rate of change in odds of hospital admission/transfer (aOR, 0.97; 95% CI, 0.95-0.99). Pathway implementation was not associated with chest radiograph use or ED length of stay.

Conclusions: Pathway implementation was associated with improved quality of care for children with asthma in a diverse, national group of EDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.02.080DOI Listing
August 2020

Aeroallergen Sensitization, Serum IgE, and Eosinophilia as Predictors of Response to Omalizumab Therapy During the Fall Season Among Children with Persistent Asthma.

J Allergy Clin Immunol Pract 2020 10 4;8(9):3021-3028.e2. Epub 2020 May 4.

Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Background: Perennial aeroallergen sensitization is associated with greater asthma morbidity and is required for treatment with omalizumab.

Objective: To investigate the predictive relationship between the number of aeroallergen sensitizations, total serum IgE, and serum eosinophil count, and response to omalizumab in children and adolescents with asthma treated during the fall season.

Methods: This analysis includes inner-city patients with persistent asthma and recent exacerbations aged 6-20 years comprising the placebo- and omalizumab-treated groups in 2 completed randomized clinical trials, the Inner-City Anti-IgE Therapy for Asthma study and the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations study. Logistic regression modeled the relationship between greater degrees of markers of allergic inflammation and the primary outcome of fall season asthma exacerbations.

Results: The analysis included 761 participants who were 62% male and 59% African American with a median age of 10 years. Fall asthma exacerbations were significantly higher in children with greater numbers of aeroallergen-specific sensitizations in the placebo group (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P < .01), but not in the omalizumab-treated children (OR, 1.08; 95% CI, 0.91-1.28; P = .37), indicating a significant differential effect (P < .01). Likewise, there was a differential effect of omalizumab treatment in children with greater baseline total serum IgE levels (P < .01) or greater baseline serum eosinophil counts (P < .01). Multiple aeroallergen sensitization was the best predictor of response to omalizumab; treated participants sensitized to ≥4 different groups of aeroallergens had a 51% reduction in the odds of a fall exacerbation (OR, 0.49; 95% CI, 0.30-0.81; P < .01).

Conclusions: In preventing fall season asthma exacerbations, treatment with omalizumab was most beneficial in children with a greater degree of allergic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2020.03.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775809PMC
October 2020

Asthma.

Pediatr Rev 2019 Nov;40(11):549-567

Division of Emergency Medicine, Children's National Medical Center, Washington, DC.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/pir.2018-0282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818355PMC
November 2019
-->