Introduction Asthma is one of the most common chronic diseases of childhood with morbidity disproportionately affecting children across different racial and/or ethnic groups and socioeconomic statuses, specifically Black children and those living in poverty. Hospitalization for asthma is a significant risk factor for future readmissions. The Hospital-to-Home (H2H) study seeks to improve asthma care and outcomes by focusing on the transition home after hospitalizations. Methods The H2H study is a pragmatic, randomized controlled trial comparing the H2H intervention to usual care. The intervention involves 12 months of care coordination from an asthma navigator. Participants are enrolled during hospitalization from either a freestanding urban children's hospital or an affiliated community hospital. The primary outcome is readmission for asthma within 12 months of index asthma-related hospital admission. Secondary outcomes include caregiver asthma-related quality of life, self-efficacy for asthma management, perceived stress, and resilience. Discussion Children admitted with asthma exacerbations represent an at-risk population, thus hospitalization offers a critical opportunity to deliver timely, meaningful interventions that can support sustained improvements in their care and improve long-term outcomes. Despite the majority of asthma hospitalizations occurring in community hospitals, past studies have focused on freestanding children's hospitals. To improve the generalizability of our findings, we also enroll children from a community hospital. Optimizing care with the H2H intervention offers an opportunity to reduce asthma morbidity in an at-risk pediatric cohort by leveraging high-touch, cost-effective asthma navigators for intensive coordination while maintaining low-touch provider oversight to ensure safety and sustainability.

OBJECTIVE:To evaluate if the Child Opportunity Index (COI) moderates associations between receiving a multimodal evidence-based asthma intervention and asthma-related emergency department (ED) reutilization among children. METHODS:We identified a prospective cohort of children ≤16 years old with ≥1 asthma-related ED visit(s) in 2022 from our city-wide asthma registry. We evaluated associations between receiving evidence-based asthma care through a locally validated intervention (exposure) and risk of ED reutilization within one year of the first ED visit (outcome) stratified by age (0-4, 5-11, 12-16 years), modeling recurrent events using survival analysis. We then tested for interactions between the COI and receiving the asthma intervention by stratifying by census tract COI 3.0 (moderator) which we dichotomized into lower (very low/low) and higher (moderate/high/very high) COI. RESULTS:There were 4125 ED encounters among 2244 children. Most lived in lower COI areas (67.2%, n = 1507). Two-hundred and eighty children (12.5%) received the multimodal evidence-based asthma intervention, which overall was associated with a reduced risk of ED reutilization (adjusted hazard ratio [aHR] 0.58, 95%CI: 0.48, 0.71). Among children 5-11 years old, this reduction was significantly less in those from lower COI areas (aHR 0.64, 83.4%CI 0.52, 0.79) than in those from higher COI areas (aHR 0.21, 83.4%CI 0.12, 0.38) (p-interaction = 0.01). The COI did not moderate associations for other age groups. CONCLUSIONS:Adjusting effective evidence-based asthma care interventions to enhance their impact for children experiencing COI-related barriers, while partnering with communities to eradicate the root causes of lower COI, may be needed to achieve more equitable outcomes.

Respiratory health is the result of genetics and socioenvironmental factors that influence optimal lung development and function. Adverse socioenvironmental exposures are linked with pediatric respiratory diseases. Because pulmonary symptomatology is nonspecific, objective assessment of respiratory health is based on pulmonary function testing. Historically, pulmonary function testing was adjusted for race. With increased recognition of race being a social rather than a biological construct, the American Thoracic Society issued guidelines in 2023 recommending a "race-neutral" approach to the interpretation of lung function, as put forth by the Global Lung Function Initiative-Global equations. Using disease examples of asthma and pulmonary involvement in sickle cell disease, we describe effects of these guidelines on disease reclassification, including identification of worse airflow obstruction in Black children, that corresponded with disease burden. Despite the greater alignment of the race-neutral approach with disease burden, there is a possibility that reclassifying disease may widen the racial gaps. For these reasons, although we recommend clinicians to routinely incorporate spirometry for assessment of respiratory disease, we suggest that in the setting of an abnormal result, they not only address the underlying disease but also assess for, and address, adverse socioenvironmental factors that are known determinants of low lung function. This contextual analysis of pulmonary function is key in providing equitable respiratory health for all children. The recommendations also identify the need for additional research on its implications among healthy children and the role of biological variables such as genetic variation that are associated with ancestry and independently associated with lower lung function.

Importance:While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. Objective:To identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab vs placebo. Design, Setting, and Participants:This is a secondary analysis of the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (MUPPITS-2) double-blind, placebo-controlled, parallel-group, randomized clinical trial comparing treatment with mepolizumab vs placebo among children with exacerbation-prone asthma in low-income urban centers in 9 US cities. Data analysis was performed from September 2022 to April 2025. Intervention:Participants were randomized to receive either mepolizumab (aged 6-11 years: 40 mg; aged 12-17 years: 100 mg) or matching placebo by subcutaneous injection once every 4 weeks for 52 weeks. Main Outcomes and Measures:The primary measurement was a transcriptomic modular analysis by RNA sequencing of nasal samples obtained during acute respiratory illnesses. Associations among upper airway transcriptional signatures, the clinical outcome of respiratory illnesses, and pulmonary functions were investigated. Results:Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants (median [IQR] age, 10.0 [9.0-13.0] years; 48 [44%] female) were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module associated with T2 inflammation (log2 fold change [FC] estimate, -0.60; false discovery rate [FDR] < .05) but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo (log2 FC estimates, 0.22-0.85; FDR < .05). Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to nonexacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus, while macrophage pathways contributed specifically to viral exacerbations. Three distinct, semiorthogonal inflammatory axes were shown to underlie the majority of the heterogeneity among exacerbations in the 2 groups. Conclusions and Relevance:The study's findings implicate multiple alternative inflammatory pathways associated with the epithelium and macrophages, as well as mucus hypersecretion, as mechanisms of residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes can independently contribute to asthma exacerbations. Trial Registration:ClinicalTrials.gov Identifier: NCT03292588.

Mepolizumab (anti-IL5 therapy) reduces asthma exacerbations in urban children with exacerbation-prone eosinophilic asthma. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with asthma exacerbations despite this therapy. In this study, we applied differential gene correlation analysis on these targeted gene co-expression modules to gain better insight into the treatment effects on correlation structure within gene networks. Mepolizumab treatment resulted in loss of correlation amongst eosinophil-specific genes but conservation and even strengthening of correlation amongst mast cell-specific genes, T2 cytokines, and airway epithelial inflammatory genes. Notably, mepolizumab induced significant gain in correlation of genes associated with multiple aspects of airway epithelial inflammation including those related to extracellular matrix production and nitric oxide synthesis, and this change was associated with a poor clinical response to mepolizumab. These findings highlight that using differential gene correlation analysis offers insight into the molecular regulatory effects of treatment on gene interactions and may lead to better understanding of disease mechanisms and therapeutic responses. ClinicalTrials.gov ID: NCT03292588.

Background Overweight/obesity is a risk factor for asthma, particularly in under-resourced children, and contributes to higher disease burden. Type 2 (T2) inflammation, a key characteristic of asthma endotypes, has been inconsistently associated with burden of obesity-related asthma, which may be due to limited overlap between different T2 features, including elevated total serum IgE level, eosinophilia, and allergen sensitization. Objective To investigate the effects of different T2 features on association of overweight/obesity with asthma burden in under-resourced children. Methods Among 2160 children aged 6 to 20 years from 4 Inner-City Asthma Consortium cohorts, the association of overweight/obesity with asthma burden (unscheduled visits, hospitalizations, exacerbations, asthma control, and pulmonary function) and the effect of T2 features (total IgE level higher than age-specific cutoffs, total eosinophils > 300 cells/µL, or sensitization to ≥2 allergens) on the association were investigated. Results The odds (odds ratio [95% CI]) of unscheduled visits were higher among those with overweight/obesity (1.35 [1.04-1.75]) and allergen sensitization (1.35 [1.02-1.80]), hospitalizations were higher among those with elevated total IgE level (2.17 [1.27-3.69]) and eosinophilia (2.80 [1.56-5.21]), and poor asthma control was higher among those with elevated total IgE level (1.27 [1.09-1.41]). Overweight/obesity and all T2 features were associated with lower forced expiratory volume in 1 second/forced vital capacity ratio. There was no synergistic or clinically significant mediating influence of any of T2 features on the association of overweight/obesity with asthma burden. Conclusion Among under-resourced children with asthma, overweight/obesity and T2 inflammation are largely independently associated with unscheduled visits and pulmonary function deficits. T2 inflammation, but not overweight/obesity, is associated with poor control and hospitalizations.

While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. To identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab vs placebo. This is a secondary analysis of the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (MUPPITS-2) double-blind, placebo-controlled, parallel-group, randomized clinical trial comparing treatment with mepolizumab vs placebo among children with exacerbation-prone asthma in low-income urban centers in 9 US cities. Data analysis was performed from September 2022 to April 2025. Participants were randomized to receive either mepolizumab (aged 6-11 years: 40 mg; aged 12-17 years: 100 mg) or matching placebo by subcutaneous injection once every 4 weeks for 52 weeks. The primary measurement was a transcriptomic modular analysis by RNA sequencing of nasal samples obtained during acute respiratory illnesses. Associations among upper airway transcriptional signatures, the clinical outcome of respiratory illnesses, and pulmonary functions were investigated. Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants (median [IQR] age, 10.0 [9.0-13.0] years; 48 [44%] female) were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module associated with T2 inflammation (log2 fold change [FC] estimate, −0.60; false discovery rate [FDR] < .05) but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo (log2 FC estimates, 0.22-0.85; FDR < .05). Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to nonexacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus, while macrophage pathways contributed specifically to viral exacerbations. Three distinct, semiorthogonal inflammatory axes were shown to underlie the majority of the heterogeneity among exacerbations in the 2 groups. The study’s findings implicate multiple alternative inflammatory pathways associated with the epithelium and macrophages, as well as mucus hypersecretion, as mechanisms of residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes can independently contribute to asthma exacerbations. ClinicalTrials.gov Identifier: NCT03292588

Background: Determining why some upper respiratory illnesses provoke asthma exacerbations remains an unmet need. Objective: We sought to identify transcriptome-wide gene expression changes associated with colds that progress to exacerbation. Methods: Two hundred eight urban children (6-17 years) with exacerbation-prone asthma were prospectively monitored for up to 2 cold illnesses. Exacerbation illnesses (Ex(+)), defined as colds leading to asthma exacerbations requiring systemic corticosteroids within 10 days, were compared to colds that resolved without exacerbation (Ex(-)). Peripheral blood and nasal lavage samples were collected at baseline and during colds for RNA sequencing. Interferon gene expression was compared between Ex(+) and Ex(-) illnesses. Generalized additive modeling revealed interferon response kinetics. Multiple linear regression models compared interferon expression to clinical variables. Results: One hundred six participants were evaluated during 154 colds. There was greater upregulation of differentially expressed interferon genes during Ex(+) illnesses compared to Ex(-). Ex(+) illnesses had greater average and steeper rise in interferon expression. Within 3 days of illness, interferon expression was positively associated with nasal rhinovirus quantity (nasal: adjusted R-2 = 0.48, P = .015; blood: adjusted R-2 = 0.22, P = .013), and interferon expression was negatively associated with percentage predicted forced expiratory volume in 1 second (nasal: beta = -0.010, P = .048; blood: beta = -0.008, P = .023). Participants with lower baseline interferon expression had shorter time to exacerbation, higher risk for exacerbation with viral illnesses, and greater increase in interferon expression during viral colds (nasal: beta = -0.80, P < .0001; blood: beta = -0.75, P < .0001). Conclusion: Dysregulated interferon responses are important contributors to asthma exacerbation risk in children. Low baseline interferon expression followed by greater upregulation of interferon pathways in airway and blood during respiratory illnesses increased exacerbation risk. Targeting this pathway in at-risk individuals holds promise for the personalized prevention of asthma exacerbations.

Rationale: Systemic corticosteroids are standard-of-care treatment for asthma exacerbations; however, little is known about whether corticosteroid effects on airway inflammatory pathways differ when added to biologic therapies targeting type 2 inflammation. Methods: 290 urban children (6-17 years) with exacerbation-prone eosinophilic asthma were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected at baseline (before treatment), post-exacerbation (5-10 days after starting systemic corticosteroids), and on treatment for RNA-sequencing. Differentially expressed genes (DEGs) were assessed using mixed effects modeling (significance threshold FDR<0.05). Results: 98 participants were evaluated following 170 exacerbation events (placebo:105, mepolizumab:65). In the placebo group, there were no significant differentially expressed genes comparing on treatment to before treatment timepoints. In the placebo group, there were 6363 significant DEGs (2734 increased, 3629 decreased) comparing post-exacerbation to on treatment. In the mepolizumab group, there were 1404 significant DEGs (664 increased, 740 decreased) comparing on treatment to before treatment (Fig1A: x-axis). In the mepolizumab group, there were 1111 significant DEGs (413 increased, 698 decreased) comparing post-exacerbation to on treatment (Figure 1A: y-axis). In the post-exacerbation versus on treatment contrasts, there were 885 overlapping significant DEGs (348 increased, 537 decreased) between the placebo and mepolizumab participants. Mepolizumab reduced expression of eosinophil-associated genes (CCL23, GATA1, CLC, PRSS33, PTGDR2, ADORA3, THBS4) on treatment, with a larger decrease post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab did not significantly alter expression of mast cell/T2 cytokine-related genes (HDC, CPA3, GATA2, TPSAB2, IL5, IL13, IL1RL1, ALOX15) on treatment; however, expression of these genes significantly decreased post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab increased expression of genes associated with epithelial and airway inflammation (CFTR, ERBB2, BMP3, TRPV4) on treatment; however, expression of these genes returned to baseline levels post-corticosteroid (FDR<0.05) (Fig1B). Conclusions: By comparing differential gene expression across treatment groups and time points, we identified overlapping DEGs related to systemic corticosteroid effects, DEGs related only to mepolizumab treatment, and clusters of functionally related genes with additive effects of mepolizumab plus systemic corticosteroids. Mepolizumab enhances the actions of oral corticosteroids on eosinophil related pathways in relation to exacerbations. Oral corticosteroids provide the added benefit of down-regulating mast cell and T2 cytokine pathways. Finally, oral corticosteroids reverse the up-regulation of epithelial inflammatory pathways that occurred during mepolizumab treatment.

BACKGROUND:T-cell responses to the individual components of allergen extracts have not been fully elucidated in subcutaneous allergen immunotherapy (SCIT). Specifically, it is unknown whether T-cell responses to immunodominant allergens are more or less sensitive to modulation, and whether allergen abundance in the immunotherapy extract influences T-cell response modulation. OBJECTIVE:To fill these gaps, we evaluated CD4+ T-cell reactivity specific to each of the main cockroach allergens in the double-blinded, placebo controlled, multicenter CRITICAL (NCT03541187) SCIT trial. METHODS:Participants aged 8-17 years with mild-to-moderate, well-controlled asthma received 12 months' dosing with cockroach SCIT (n = 20) or placebo (n = 26). Peripheral blood mononuclear cells were isolated before and after 12 months of therapy. CD4+ T-cell responses at baseline and after treatment were assessed using overlapping peptide pools derived from 11 well-defined cockroach allergens and intracellular cytokine staining for IL-4, IFN-γ, and IL-10 production. T-cell responses were evaluated for magnitude, cytokine polarization, allergen immunodominance, and correlation with allergen content in the cockroach SCIT extract. RESULTS:SCIT modulation was more prominent in participants with the strongest and most TH2-polarized responses. Downmodulation was observed against Bla g 5 and Bla g 9, the most dominantly recognized allergens in the population study. Furthermore, effective modulation was observed independent of allergen content in the cockroach SCIT extract. CONCLUSION:Immunodominant responses are effectively modulated by SCIT, and this effect is independent of allergen abundance in the extract utilized for SCIT.

BACKGROUND:Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses. METHODS:Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 respiratory pathogens. We performed RNA sequencing on 147 swabs (n = 144 participants) collected prior to SARS-CoV-2 infection and 391 swabs (n = 165 participants) during and before rhinovirus infection. RESULTS:Participants with rhinovirus infection in the previous 30 days were at 48% lower risk of SARS-CoV-2 infection (adjusted hazard ratio, 0.52; P = .034). Among participants with SARS-CoV-2 infection, recent rhinovirus infection was associated with 9.6-fold lower SARS-CoV-2 viral load (P = .0031). Higher preinfection expression of 57 genes was associated with lower SARS-CoV-2 viral load, including 24 antiviral defense genes; 22 of these were induced by rhinovirus infections. Relative to adults, children expressed higher levels of the antiviral gene signature (P = .014) and were at 2.2-fold increased risk for rhinovirus infections. CONCLUSIONS:Rhinovirus infections, which trigger increased expression of antiviral airway genes, are linked to a lower risk of SARS-CoV-2 infection. Frequent rhinovirus infections may enhance this protective gene profile, partially explaining why children experience milder SARS-CoV-2 infections compared to adults. CLINICAL TRIALS REGISTRATION:NCT04375761.

Multiple early life environmental exposures are thought to influence childhood asthma incidence. The coronavirus disease 2019 (COVID-19) pandemic resulted in changes in air pollution levels and a marked disruption in the circulation of childhood respiratory viruses. Both air pollution and respiratory viruses have been implicated in the development of asthma and early childhood wheeze. Human behavior and daily routine practices, including family gatherings and daycare attendance, were impacted profoundly by the COVID-19 pandemic and the associated mitigation measures. The changes to human behavior and social interactions that occurred during the pandemic have and will likely continue to impact chronic diseases, including the development of asthma. This rostrum explores how childhood asthma incidence might be affected by the COVID-19 pandemic and its associated public health mitigation measures. Recently completed and ongoing clinical trials being conducted in the infant and toddler population and assessing allergic outcomes may be well positioned to examine the impact of the pandemic on asthma incidence and time to asthma onset.

BACKGROUND:It is unknown whether nasal corticosteroid (NCS) or inhaled corticosteroid (ICS) use impacts the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVES:We sought to examine the associations of NCS and ICS use with the risk of SARS-CoV-2 infection among individuals with allergic rhinitis or asthma. METHODS:This is a prospective, multicenter, SARS-CoV-2 surveillance study of households with children. Nasal swabs were obtained from participants every 2 weeks with additional collections based on coronavirus disease 2019-related symptoms. In our primary adjusted models, we examined the association of NCS or ICS use at study entry (in participants with allergic rhinitis or asthma, respectively) with the time to the first SARS-CoV-2-positive quantitative PCR testing using Cox proportional hazard regression. RESULTS:There were 2211 participants in the 1113 households included. The associations of NCS and ICS use with the risk of SARS-CoV-2 infection were modified by age (P for both interactions <.05). NCS and ICS use were individually associated with higher risks of SARS-CoV-2 infection among adults (adjusted hazard ratio [aHR] = 1.88, 95% CI: 1.14-3.12, P = .01, and aHR = 2.15, 95% CI: 1.003-4.63, P = .049, respectively). The association of NCS use with the risk of SARS-CoV-2 infection in adults was consistent in a series of sensitivity analyses. There was no association of NCS or ICS use with the risk of SARS-CoV-2 infection in children. CONCLUSION:Our findings suggest that the risk of SARS-CoV-2 infection is increased in adults who use NCS but not in children. Similar, albeit less consistent, age-dependent findings were observed for ICS use. While the results of this observational study should be interpreted with caution, they emphasize the need to conduct studies to understand potential mechanisms that could explain these findings.

Background: While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. We aimed to identify the multiple distinct molecular mechanisms implicated in asthma exacerbations in children by contrasting exacerbations among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab versus placebo.Methods: We performed transcriptomic modular analysis of nasal samples obtained during acute respiratory illnesses from urban children with exacerbation-prone eosinophilic asthma enrolled in the MUPPITS-2 clinical trial, which compared treatment with mepolizumab versus placebo. We investigated associations among upper airway transcriptional signatures, respiratory illnesses that resulted in exacerbations, pulmonary function, and biomarkers of T2 inflammation.Findings: Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module related to T2 inflammation but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo. Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to non-exacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus while macrophage pathways occurred specifically in viral exacerbations.Interpretation: Our findings implicate multiple alternative inflammatory pathways related to the epithelium and macrophages, as well as mucus hypersecretion, as probable mechanisms responsible for residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes contribute to asthma exacerbations.Funding: The research reported in this publication was supported by NIH-NIAID award numbers 5UM1AI114271, UM1AI160040, and UM2AI117870, with additional support provided through award numbers UL1TRG01422, UL1RR025741, UL1TR000150, UL1TR001422, UL1 TR002535, UL1TR001876, and 5UL1TR001425–03. Additional support was also provided through an unrestricted grant from GlaxoSmithKline.Declaration of Interest: All authors except A. Togias and P. Becker report grants from NIH/NIAID during the conduct of study. W. Busse reports consulting fees from Novartis, GlaxoSmithKline, Genentech, Sanofi, AstraZeneca and Regeneron, royalties from Elsevier outside the submitted work. M. Gill reports an honorarium for and support for travel to the 2017 AAAAI meeting during the conduct of study and monetary compensation from the American Academy of Pediatrics for her work teaching the biannual Pediatrics board review course, PREP The Course. K. Hershey reports grants from Adare, during the conduct of the study. D. Jackson reports personal fees from Novartis, Pfizer, Regeneron, AstraZeneca, Sanofi and Vifor Pharma, grants and personal fees from GlaxoSmithKline and grants from NIH/NHLBI, outside the submitted work. M. Kattan reports personal fees from Regeneron, outside the submitted work. R. Gruchalla reports government employment from Center for Biologics Evaluation and Research as well as personal fees from Consulting Massachusetts Medical Society, outside the submitted work. A. Liu reports personal fees from Phadia ThermoFisher as consulting honoraria, grants and non-financial support from ResMed/Propeller Health, non-financial support from Revenio, grants and personal fees from Avillion and personal fees from Labcorp, outside the submitted work. L. Bacharier reports book royalties from Elsevier, consulting fees from Sanofi, Regeneron, Genentech, GlaxoSmithKline, DBV technologies, Teva, Medscape, Kinaset, OM Pharma and AstraZeneca, honoraria from Sanofi, Regeneron and GlaxoSmithKline, participation in advisory board for DBV Technologies, AstraZeneca and Vertex, leadership role in American Academy of Allergy Asthma & Immunology and American Board of Allergy and Immunology and medical writing services for Sanofi/Regeneron. J. Gern reports consulting fees from AstraZeneca and Meissa Vaccines, two patents related to the methods to enhance the production of rhinoviruses and stock options with Meissa Vaccines. S. Teach reports grants from NIH–NHLBI, payment from Medscape and personal fees from Uptodate. S. Lynch reports personal fees from Siolta Therapeutics, personal fees from Sanofi, a patent Reductive prodrug cancer chemothera (Stan449-PRV) issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection; WO 2010091189 A1 with royalties paid to KaloBios Inc., a patent Therapeutic microbial consortium for induction of immune tolerance licensed to Siolta Therapeutics, a patent Systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent Nitroreductase enzymes. US 7687474 B2 issued, a patent Sinusitis diagnostics and treatments WO 2013155370 A1 issued, a patent Methods and systems for phylogenetic analysis US 20120264637 A1 issued, and a patent methods and compositions relating to epoxide hydrolase genes issued to Siolta Therapeutics and reports that she is a co-founder of Siolta Therapeutics, a start up company that is developing a mixed-species microbial oral therapeutic for induction of immune tolerance. All other authors declare no competing interests.Ethical Approval: The protocol was approved by a central IRB. The legal guardians of all study participants provided written informed consent and children provided assent.

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 IFN 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.

New faculty orientation (NFO) programs are shown to increase faculty satisfaction, enhance collaboration, and support promotion, retention, and academic success. In an effort led by a clinical psychologist, the Children’s National Hospital (CNH) NFO was developed, piloted, and is in its 3rd year. Data are shared regarding program development process, feasibility, and acceptability. In 2020, CNH faculty were surveyed about their new faculty member experience. CNH leaders were interviewed about important topics to include in an NFO. In FY22, the NFO was piloted across 15 Divisions. Year 2 (FY23) invited all new early career faculty. Year 3 (FY24) invited all new faculty. Feedback was obtained via REDCap after meetings and before/after the 10-month program. In 2020, 62

Background: In the United States, Black and Latino children with asthma are more likely than White children with asthma to require emergency department visits or hospitalizations because of an asthma exacerbation. Although many cite patient-level socioeconomic status and access to health care as primary drivers of disparities, there is an emerging focus on a major root cause of disparities-systemic racism. Current conceptual models of asthma disparities depict the historical and current effects of systemic racism as the foundation for unequal exposures to social determinants of health, environmental exposures, epigenetic factors, and differential healthcare access and quality. These ultimately lead to biologic changes over the life course resulting in asthma morbidity and mortality. Methods: At the 2022 American Thoracic Society International Conference, a diverse panel of experts was assembled to identify gaps and opportunities to address systemic racism in childhood asthma research. Panelists found that to examine and address the impacts of systemic racism on children with asthma, researchers and medical systems that support biomedical research will need to 1) address the current gaps in our understanding of how to conceptualize and characterize the impacts of systemic racism on child health, 2) design research studies that leverage diverse disciplines and engage the communities affected by systemic racism in identifying and designing studies to evaluate interventions that address the racialized system that contributes to disparities in asthma health outcomes, and 3) address funding mechanisms and institutional research practices that will be needed to promote antiracism practices in research and its dissemination. Results: A thorough literature review and expert opinion discussion demonstrated that there are few studies in childhood asthma that identify systemic racism as a root cause of many of the disparities seen in children with asthma. Community engagement and participation in research studies is essential to design interventions to address the racialized system in which patients and families live. Dissemination and implementation studies with an equity lens will provide the multilevel evaluations required to understand the impacts of interventions to address systemic racism and the downstream impacts. To address the impacts of systemic racism and childhood asthma, there needs to be increased training for research teams, funding for studies addressing research that evaluates the impacts of racism, funding for diverse and multidisciplinary research teams including community members, and institutional and financial support of advocating for policy changes based on study findings. Conclusions: Innovative study design, new tools to identify the impacts of systemic racism, community engagement, and improved infrastructure and funding are all needed to support research that will address impacts of systemic racism on childhood asthma outcomes.