Helping Low-Income Families Manage Childhood Asthma: Solutions for Healthcare & Beyond

Asthma is the most common childhood chronic illness, affecting more than seven million children nationwide. Managing chronic illness in a child is challenging for any family. Among the challenges is constant fear of an acute episode, a complex regimen of medications given daily or many times each day, frequent changes in prescriptions or dosages, coordinating multiple healthcare providers, and helping a child have as "normal" and active a childhood as his/her condition allows. Low-income children of color bear a heavier asthma burden than their white or more affluent peers. Those low-income children who live in urban areas such as Baltimore, Chicago, Los Angeles, and New York are particularly vulnerable. Families with limited resources struggle to provide their children with asthma the support that these children need

Recurrent and High‐frequency Use of the Emergency Department by Pediatric Patients

Objectives The authors sought to describe the epidemiology of and risk factors for recurrent and high‐frequency use of the emergency department (ED) by children. Methods This was a retrospective cohort study using a database of children aged 0 to 17 years, inclusive, presenting to 22 EDs of the Pediatric Emergency Care Applied Research Network (PECARN) during 2007, with 12‐month follow‐up after each index visit. ED diagnoses for each visit were categorized as trauma, acute medical, or chronic medical conditions. Recurrent visits were defined as any repeat visit; high‐frequency use was defined as four or more recurrent visits. Generalized estimating equations (GEEs) were used to measure the strength of associations between patient and visit characteristics and recurrent ED use. Results A total of 695,188 unique children had at least one ED visit each in 2007, with 455,588 recurrent ED visits in the 12 months following the index visits. Sixty‐four percent of patients had no recurrent visits, 20% had one, 8% had two, 4% had three, and 4% had four or more recurrent visits. Acute medical diagnoses accounted for most visits regardless of the number of recurrent visits. As the number of recurrent visits per patient rose, chronic diseases were increasingly represented, with asthma being the most common ED diagnosis. Trauma‐related diagnoses were more common among patients without recurrent visits than among those with high‐frequency recurrent visits (28% vs. 9%; p < 0.001). High‐frequency recurrent visits were more often within the highest severity score classifications. In multivariable analysis, recurrent visits were associated with younger age, black or Hispanic race or ethnicity, and public health insurance. Conclusions Risk factors for recurrent ED use by children include age, race and ethnicity, and insurance status. Although asthma plays an important role in recurrent ED use, acute illnesses account for the majority of recurrent ED visits. Resumen Objetivos Describir la epidemiología y los factores de riesgo de revista e hiperfrecuentación del servicio de urgencias (SU) por parte de los pacientes pediátricos. Metodología Estudio de cohorte retrospectivo mediante una base de datos de niños entre 0 y 17 años inclusive, que acudieron a 22 SU de la Pediatric Emergency Care Applied Research Network durante 2007, con un seguimiento de 12 meses tras cada visita índice. Los diagnósticos del SU de cada visita se clasificaron como traumatológico, médico agudo o enfermedades médicas crónicas. Las revisitas se definieron como cualquier visita repetida; la hiperfrecuentación se definió como cuatro o más revisitas. Se utilizaron ecuaciones de estimación generalizada para medir la fuerza de las asociaciones entre las características al paciente y la visita y la revisita del SU. Resultados Un total de 695.188 niños tuvieron al menos una visita al SU en 2007, con 455.588 revisitas al SU en los 12 meses tras las visitas índice. Un 64% de los pacientes no tuvieron revisitas, un 20% tuvo una, un 8% tuvo dos, un 4% tuvo tres y un 4% tuvo cuatro o más revisitas. Los diagnósticos médicos agudos representan la mayoría de las visitas, con independencia del número de revisitas. A medida que el número de revisitas por paciente aumentaba, las enfermedades crónicas estaban más representadas, y el asma fue el diagnóstico más común en el SU. Los diagnósticos relacionados con lo traumatológico fueron más frecuentes entre los pacientes sin revisitas que entre aquéllos con hiperfrecuentación (28% vs. 9%; p < 0,001). La alta frecuencia de revisitas fue más frecuente en las clasificaciones de gravedad más altas. En el análisis multivariable, las revisitas se asociaron con una edad más joven, raza o etnia negra o hispana, y la tenencia de un seguro de salud público. Conclusiones Los factores de riesgo para la revisita al SU por los niños incluyen la edad, la raza o etnia, y el tipo de seguro médico. Aunque el asma juega un papel importante en la revisita al SU, las enfermedades agudas representan la mayoría de la revistas al SU.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106853/1/acem12347.pd

Stakeholder engagement in eight comparative effectiveness trials in African Americans and Latinos with asthma

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies. METHODS: Using the method content analysis of cases, we identified themes regarding the types of stakeholders, methods of engagement, input from the stakeholders, changes made to the research protocols and processes, and perceived benefits and challenges of the engagement process. We used summaries from meetings of the eight teams, results from an engagement survey, and the final research reports as our data source to obtain detailed information. The descriptive data were assessed by multiple reviewers using inductive and deductive qualitative methods and discussed in the context of engagement literature. RESULTS: Stakeholders participated in the planning, conduct, and dissemination phases of all eight asthma studies. All the studies included clinicians and community representatives as stakeholders. Other stakeholders included patients with asthma, their caregivers, advocacy organizations, and health-system representatives. Engagement was primarily by participation in advisory boards, although six of the eight studies (75%) also utilized focus groups and one-on-one interviews. Difficulty finding a time and location to meet was the most reported challenge to engagement, noted by four of the eight teams (50%). Other reported challenges and barriers to engagement included recruitment of stakeholders, varying levels of enthusiasm among stakeholders, controlling power dynamics, and ensuring that stakeholder involvement was reflected and had true influence on the project. CONCLUSION: Engagement-driven modifications led to specific changes in study design and conduct that were felt to have increased enrollment and the general level of trust and support of the targeted communities. The level of interaction described, between investigators and stakeholders in each study and between investigator-stakeholder groups, is-we believe-unprecedented and may provide useful guidance for other studies seeking to improve the effectiveness of community-driven research

Feasibility of Screening Patients With Nonpsychiatric Complaints for Suicide Risk in a Pediatric Emergency Department: A Good Time to Talk?

Screening children for suicide risk when they present to the emergency department (ED) with nonpsychiatric complaints could lead to better identification and treatment of high-risk youth. Before suicide screening protocols can be implemented for nonpsychiatric patients in pediatric EDs, it is essential to determine whether such efforts are feasible

Epithelial-Associated Inflammatory Pathways Underlie Residual Asthma Exacerbations in Urban Children Treated with Mepolizumab Therapy

Rationale: Identification of airway inflammatory pathways in asthma has proven essential to understanding mechanisms of disease and has led to effective personalized treatment with biologic therapies. However, relatively little is known about patterns of airway inflammation at the time of respiratory illnesses and how such patterns relate to responsiveness to biologic therapies. Methods: The MUPPITS-1 (n=106) and MUPPITS-2 (n=290) studies investigated asthma exacerbations in urban children with exacerbation-prone asthma and ≥150/microliter blood eosinophils. Children in both studies received guidelines-based asthma care; in MUPPITS-2, participants were additionally randomized (1:1) to placebo or mepolizumab. Nasal lavage samples were collected during respiratory illnesses for RNA-sequencing and analyzed by modular analysis to assess genome-wide expression patterns associated with exacerbation illnesses. Results: Among 284 illnesses, exacerbations that occurred in the absence of mepolizumab therapy showed significantly higher upregulation of eosinophil associated inflammatory pathways (fold change values [FC]=1.27-1.43, p-values\u3c0.05), including a Type-2 inflammation module composed of eosinophil, mast cell, and IL-13 response genes. In contrast, exacerbations that occurred while on mepolizumab therapy showed significantly higher upregulation of several epithelial inflammatory pathways (FC=1.36-1.64, p-values\u3c0.05) including TGF-β/Smad3 signaling, extracellular matrix production, and epidermal growth factor receptor signaling. Conclusions: These results indicate that novel inflammatory pathways, likely originating from the airway epithelium and distinct from Type-2 or eosinophilic inflammation, drive residual exacerbations that occur in children treated with mepolizumab therapy added to guideline-based care. These findings identify likely mechanisms of persistent disease expression in these children despite significant depletion of eosinophils and can identify novel treatment targets for future studies

Mepolizumab Alters Regulation of Airway Type-2 Inflammation in Urban Children with Asthma by Disrupting Eosinophil Gene Expression but Enhancing Mast Cell and Epithelial Pathways

Rationale: Mepolizumab (anti-IL5) reduces asthma exacerbations in urban children. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with exacerbations despite this therapy. To understand mepolizumab’s precise impact on these pathways, we assess gene co-expression and loss of correlation, “decoherence,” using differential co-expression network analyses. Methods: 290 urban children (6-17 years) with exacerbation-prone asthma and blood eosinophils ≥150/microliter were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected before and during treatment for RNA-sequencing. Differential co-expression of gene networks was evaluated to assess interactions and regulatory aspects of type-2 and eosinophilic airway inflammation. Results: Mepolizumab, but not placebo, significantly reduced the overall expression of an established type-2 inflammation gene co-expression module (fold change=0.77, p=0.002) enriched for eosinophil, mast cell, and epithelial IL-13 response genes (242 genes). Mepolizumab uncoupled co-expression of genes in this pathway. During mepolizumab, but not placebo treatment, there was significant loss of correlation among eosinophil-specific genes including RNASE2 (EDN), RNASE3 (ECP), CLC, SIGLEC8, and IL5RA contrasting a reciprocal increase in correlation among mast cell-specific genes (TPSAB1, CPA3, FCER1A), T2 cytokines (IL4, IL5, and IL13), and POSTN. Conclusions: These results suggest mepolizumab disrupts the regulatory interactions of gene co-expression among airway eosinophils, mast cells and epithelium by interrupting transcription regulation in eosinophils with enhancement in mast cell and epithelial inflammation. This paradoxical effect may contribute to an incomplete reduction of asthma exacerbations and demonstrates how differential co-expression network analyses can identify targets for more precise therapies

Down-Modulation of Cockroach (CR) Allergen-specific Th2 Cell Responses Following Subcutaneous German Cockroach Allergen Immunotherapy (SCIT)

Rationale: The responses of T cells to subcutaneous allergen immunotherapy (SCIT) are not fully elucidated. We conducted a functional immunological evaluation of cockroach (CR) allergen-specific CD4+ T cell reactivity in the double-blinded, placebo-controlled, multi-center CRITICAL study. Methods: Participants (8-17 years of age) with mild to moderate, well-controlled asthma received 12 months of maintenance dosing of CR SCIT (n=20) or placebo (n=26). Peripheral blood mononuclear cells (PBMC) were isolated prior to, 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 CR allergens and intracellular cytokine staining for IL-4, IFNg, and IL-10 production. T cell responses were further evaluated in terms of magnitude, cytokine polarization, and allergen immunodominance. Results: Significant down-modulation of the total magnitude of CD4+ T cell responses was observed with SCIT but not placebo, with a significant change between groups (-4.46±0.82 vs. −1.81±0.72, respectively, p = 0.020). Responses were driven by a decrease in IL-4 (-4.87±0.86 vs. −1.09±0.75, p = 0.002) with unaltered IFNg and IL-10 production, reflecting a shift towards a Th1 polarization profile (1.35±0.58 vs. −0.37±0.50, in SCIT and placebo respectively, p = 0.031). The largest effects were observed against the allergens Bla g 5 and Bla g 9, which are dominantly recognized, suggesting that dominant responses are susceptible to modulation. Conclusions: Our results demonstrate a significant down-regulation of CR-specific Th2 cell responses in urban children with asthma who received SCIT, compared with those who received placebo

Distinct Airway Inflammatory Pathways Associated with Asthma Exacerbations are Modulated by Mepolizumab Therapy in Children

Rationale: Identification of specific airway inflammatory pathways can lead to effective personalized treatment with biologics in asthma and insights to mechanisms of action. Methods: 290 urban children with exacerbation-prone asthma and ≥150/mm3 blood eosinophils were randomized (1:1) to placebo or mepolizumab added to guideline-based care. Nasal lavage samples were collected at randomization and during treatment for RNA-sequencing, and analyzed by cell-deconvolution modular analysis to assess genome-wide expression patterns associated with exacerbation number and effect of treatment. Results: Mepolizumab significantly reduced the frequency of exacerbations compared to placebo. At randomization, there were no differences in expression between treatment groups; multiple modules were subsequently differentially expressed during mepolizumab but not placebo treatment. Furthermore, expression levels of multiple modules were associated with the exacerbation number during the study, with distinct relationships observed in the placebo and/or mepolizumab groups. Notably, higher expression at randomization of an eosinophil-associated module enriched for Type-2 genes including IL4, IL5, and IL13, was associated with increased exacerbations in placebo (β=0.19, p\u3c0.001), but not mepolizumab-treated children (interaction p\u3c0.01). Furthermore, mepolizumab treatment reduced expression of this module (Fold-change=0.62, p\u3c0.001). In contrast, higher expression at randomization of an eosinophil-associated module enriched for eosinophil activation (e.g. CD9) and mucus hypersecretion (e.g. MUC5AC) genes was associated with exacerbation number in both groups throughout the study (β=0.18, p\u3c0.01) and was unaltered by mepolizumab therapy. Conclusions: Multiple distinct airway inflammation patterns were identified associated with exacerbation frequency. These findings identify inflammatory endotypes and indicate likelihood and potential mechanisms of a beneficial clinical response to mepolizumab therapy to prevent exacerbations

Research Priorities in Pediatric Asthma Morbidity: Addressing the Impacts of Systemic Racism on Children with Asthma in the United States. An Official American Thoracic Society Workshop Report.

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

Variation in Ancillary Testing among Pediatric Asthma Patients Seen in Emergency Departments

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72605/1/j.aem.2007.01.016.pd