Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Screening for sleep disordered breathing among children hospitalized for asthma exacerbation.

Background: Sleep disordered breathing (SDB) may exacerbate asthma and is a treatable comorbidity.

Objective: To design and implement a screening process for SDB in patients hospitalized for asthma exacerbation using quality improvement (QI) methods. We sought to improve screening for SDB from zero to 60% from July 2019 to December 2020.

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

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood.

Identifying asthma-related risks during hospitalization using the child asthma risk assessment tool.

The Child Asthma Risk Assessment Tool (CARAT) identifies risk factors for asthma morbidity. We hypothesized that CARAT-identified risk factors (using a CARAT adapted for inpatient use) would be associated with future healthcare utilization and would identify areas for intervention. We reviewed CARAT data collected during pediatric asthma admissions from 2010-2015, assessing for risk factors in environmental, medical, and social domains and providing prompts for inpatient (specialist consultation or social services engagement) and post-discharge interventions (home care visit or home environmental assessment).

Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis.

Background: Asthma prevalence and severity have markedly increased with urbanisation, and children in low-income urban centres have among the greatest asthma morbidity. Outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

Background: Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry.

Methods: We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American-specific haplotype.

Safety of Live Attenuated Influenza Vaccine in Children With Asthma.

Background And Objectives: Asthma is considered a precaution for use of quadrivalent live attenuated influenza vaccine (LAIV4) in persons aged ≥5 years because of concerns for wheezing events. We evaluated the safety of LAIV4 in children with asthma, comparing the proportion of children with asthma exacerbations after LAIV4 or quadrivalent inactivated influenza vaccine (IIV4).

Methods: We enrolled 151 children with asthma, aged 5 to 17 years, during 2 influenza seasons.

Seasonal airway microbiome and transcriptome interactions promote childhood asthma exacerbations.

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.

Dexamethasone Versus Prednisone in Children Hospitalized With Asthma Exacerbation.

Objectives: Dexamethasone is increasingly used for the management of children hospitalized with asthma in place of prednisone, yet data regarding the effectiveness of dexamethasone in children with asthma exacerbation severe enough to require hospitalization are limited. Our objective is to compare the effectiveness of dexamethasone versus prednisone in children hospitalized with an asthma exacerbation on 30-day reutilization.

Methods: We conducted a retrospective cohort study at an urban, quaternary children's hospital of children aged 4 to 17 years, hospitalized from January 1, 2014 to December 31, 2017, with a primary discharge diagnosis of asthma.

Treatment by biomarker-informed endotype vs guideline care in children with difficult-to-treat asthma.

Background: Asthma is heterogeneous, contributing to difficulty in disease management.

Objective: To develop a biomarker-informed treatment model for difficult-to-treat (DTT) asthma and conduct a pilot feasibility study.

Methods: School-aged children (n = 21) with DTT asthma were enrolled and completed 3 medical visits (V1-V3).

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

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.

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

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.

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

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.

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

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.

Serum IL-6: A biomarker in childhood asthma?

Serum IL-6 was associated with asthma exacerbation risk but not with symptoms or lung function in urban children; further studies to evaluate the role of IL-6 in the life course of asthma are needed.

Weighing in on asthma: Insights on BMI, magnesium, and hospitalizations from the Ohio Pediatric Asthma Repository.

Little is known about weight status and its effects on clinical course during hospitalization for asthma exacerbation. We sought to evaluate associations between weight status, specifically body mass index (BMI), with inpatient clinical course and clinical history. We retrospectively analyzed data from 2012 to 2013 on children hospitalized for asthma exacerbation in a state-wide longitudinal cohort, the Ohio Pediatric Asthma Repository.

Distinct nasal airway bacterial microbiotas differentially relate to exacerbation in pediatric patients with asthma.

Background: In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development.

Objective: We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes.

Methods: Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling.

Transcriptome networks identify mechanisms of viral and nonviral asthma exacerbations in children.

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation.

Management/Comorbidities of School-Aged Children with Asthma.

Asthma is a complex heterogeneous disease characterized by reversible airflow obstruction. After appropriate diagnosis, the management in school-aged children centers on 3 broad domains: pharmacologic treatment, treatment of underlying comorbidities, and education of the patient and caregivers. It is important to understand that the phenotypic differences that exist in the school-aged child with asthma may impact underlying comorbid conditions as well as pharmacologic treatment choices.

A computerized decision support tool to implement asthma guidelines for children and adolescents.

Background: Multicenter randomized controlled trials (RCTs) for asthma management that incorporate usual-care regimens could benefit from standardized application of evidence-based guidelines.

Objective: We sought to evaluate performance of a computerized decision support tool, the Asthma Control Evaluation and Treatment (ACET) Program, to standardize usual-care regimens for asthma management in RCTs.

Methods: Children and adolescents with persistent uncontrolled asthma living in urban census tracts were recruited into 3 multicenter RCTs (each with a usual-care arm) between 2004 and 2014.