Publications by authors named "John Kroner"

Importance: In the absence of evidence of clinical utility, the United States' Centers for Disease Control and Prevention does not currently recommend the assessment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike-protein antibody levels. Clinicians and their patients, especially immunocompromised patients, may benefit from an adjunctive objective clinical laboratory measure of risk, using SARS-CoV-2 serology.

Objective: The aim of this study is to estimate the association between SARS-CoV-2 spike-protein targeted antibody levels and clinically relevant outcomes overall and among clinically relevant subgroups, such as vaccine and immunocompetency statuses.

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The skin is a major immune organ and skin barrier dysfunction is a major risk factor for the development of the inappropriate immune response seen in allergic disease. Skin barrier disruption alters the landscape of antigens experienced by the immune system and the downstream impacts on the antibody repertoire remain poorly characterized, particularly for the IgE isotype responsible for allergic specificity and in early life, when allergic disease is developing. In this study, we sequenced antibody gene repertoires from a large and well-characterized cohort of children with atopic dermatitis and found that food sensitization was associated with lower mutation frequencies in the IgE compartment.

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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).

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Background: In addition to its involvement in both the innate and adaptive immune systems, vitamin D has been found to affect keratinocyte function and proliferation, suggesting a possible role for vitamin D in cutaneous allergic sensitization.

Objective: To explore the role of circulating vitamin D levels in allergic sensitization.

Methods: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in a subset of children (N = 323) enrolled in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort, a prospective early life cohort of children with atopic dermatitis.

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Background: The atopic march has been studied mostly in White populations, biasing our current paradigms.

Objective: We sought to define the atopic march in Black and White children and explore mechanisms for racial differences.

Methods: Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n = 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children.

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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.

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Background: Low epidermal filaggrin (FLG) is a risk factor for atopic dermatitis (AD) and allergic comorbidity. FLG mutations do not fully explain the variation in epidermal FLG levels, highlighting that other genetic loci may also regulate FLG expression.

Objective: We sought to identify genetic loci that regulate FLG expression and elucidate their functional and mechanistic consequences.

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Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine important in initiation of allergic inflammation. Single nucleotide polymorphisms (SNPs) in TSLP are associated with asthma, yet studies have shown inconsistent associations between circulating TSLP and asthma. Studies that integrate the combined effects of TSLP genotype, TSLP mRNA, circulating TSLP levels, and asthma outcome are lacking.

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Background: Children with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity.

Objective: We sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity.

Methods: We studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations.

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Background: Second-hand smoke (SHS) exposure is associated with paediatric asthma, and oxidative stress is believed to play a role in mediating this association. The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) is important for the defence against oxidative stress.

Objective: To explore interactions between NFE2L2 genotype and SHS exposure in paediatric asthma risk.

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Background: Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus, although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their associations with AD severity, barrier function, and epidermal gene expression in the first US early-life cohort of children with AD, the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH).

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Background: Nonlesional skin in atopic dermatitis (AD) is abnormal, but the pathobiology of lesional and nonlesional skin and the definition of endotypes are poorly understood.

Objective: To define lesional and nonlesional endotypes of AD by building the first US-based early-life prospective cohort of children with AD, the Mechanisms of Progression from AD to Asthma in Children cohort.

Methods: We assessed lesional and nonlesional skin transepidermal water loss, filaggrin (FLG) and alarmin (S100A8, S100A9) expression, staphylococcal colonization, and patterns of aeroallergen and food sensitization to define nonlesional and lesional phenotypes and endotypes.

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Early sensitization is ~50% higher in children with atopic dermatitis compared to children from a high-risk allergy cohort with comparable rates of parental atopy. AD may increase sensitization risk over heredity alone.

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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.

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Background: Asthma phenotypes are currently not amenable to primary prevention or early intervention because their natural history cannot be reliably predicted. Clinicians remain reliant on poorly predictive asthma outcome tools because of a lack of better alternatives.

Objective: We sought to develop a quantitative personalized tool to predict asthma development in young children.

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Background: Asthma is an allergic airway inflammation-driven disease that affects more than 300 million people world-wide. Targeted therapies for asthma are largely lacking. Although asthma symptoms can be prevented from worsening, asthma development cannot be prevented.

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Background: Large-scale, multisite studies in which researchers evaluate patient- and systems-level factors associated with pediatric asthma exacerbation outcomes are lacking. We sought to investigate patient-level risks and system-level practices related to physiologic readiness for discharge (PRD) in the prospective Ohio Pediatric Asthma Repository.

Methods: Participants were children ages 2 to 17 years admitted to an Ohio Pediatric Asthma Repository hospital for asthma exacerbation.

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Background: Adequate nutrition is essential for growth in children with cystic fibrosis (CF). The new CF Foundation Clinical Practice Guidelines bring attention to monitoring macronutrient intake as well as total energy.

Methods: Dietary intake of 75 preschool children with CF and pancreatic insufficiency was examined and compared to the Clinical Practice Guidelines.

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Objectives: To examine treatment adherence among children and adolescents with chronic migraine who volunteered to be in a clinical trial using 3 measures: treatment session attendance, therapy homework completion, and preventive medication use by daily diary.

Materials And Methods: Analyses are secondary from a trial of 135 youth aged 10 to 17 years diagnosed with chronic migraine and with a Pediatric Migraine Disability Score over 20. Participants were randomly assigned to cognitive-behavioral therapy plus amitriptyline (CBT+A, N=64) or headache education plus amitriptyline (HE+A, N=71).

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Unlabelled: We compared headache frequency trajectories between clinical trial participants who received cognitive-behavioral therapy (CBT) and amitriptyline (CBT+A) or headache education (HE) and amitriptyline (HE+A) to determine if there was a differential time course of treatment response between the groups. One hundred thirty-five patients (age 10-17 years) diagnosed with chronic migraine participated, attending 8 one-hour one-on-one CBT or HE sessions with a trained psychologist for 8 weekly sessions, 2 sessions at weeks 12 and 16, and a post-treatment visit at week 20. Participants kept daily headache diaries and completed take-home assignments between visits.

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Objective: The purpose of this investigation was to examine treatment adherence to medication and lifestyle recommendations among pediatric migraine patients using electronic monitoring systems.

Background: Nonadherence to medical treatment is a significant public health concern, and can result in poorer treatment outcomes, decreased cost-effectiveness of medical care, and increased morbidity. No studies have systematically examined adherence to medication and lifestyle recommendations in adolescents with migraine outside of a clinical trial.

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Objective: The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline.

Background: Chronic migraine negatively affects children's home, school, and social activities. Preventive medication therapy is suggested for 5 or more headaches per month.

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