Pediatric asthma incidence rates in the United States from 1980 to 2017.

Background: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective.

Objective: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history.

Methods: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017.

Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood.

Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry.

Disease-associated KIF3A variants alter gene methylation and expression impacting skin barrier and atopic dermatitis risk.

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3a mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD.

Biofilm propensity of Staphylococcus aureus skin isolates is associated with increased atopic dermatitis severity and barrier dysfunction in the MPAACH pediatric cohort.

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).

Simultaneous skin biome and keratinocyte genomic capture reveals microbiome differences by depth of sampling.

Novel skin tape strip method allows for simultaneous collection of the skin microbiome and underlying host DNA and RNA, and reveals that microbial ecology is dependent on the depth of sampling.

Events in Normal Skin Promote Early-Life Atopic Dermatitis-The MPAACH Cohort.

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.

Atopic dermatitis independently increases sensitization above parental atopy: The MPAACH study.

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.

genetic variation increases asthma risk in children with secondhand smoke exposure.

Objective: We previously reported that children exposed to secondhand smoke (SHS) that carried variants in the NAT1 gene had over two-fold higher hair cotinine levels. Our objective was to determine if NAT1 polymorphisms confer increased risk for developing asthma in children exposed to SHS.

Methods: White participants in the Cincinnati Childhood Allergy and Air Pollution Study ( = 359) were genotyped for 10 variants.

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.

Asthma as an outcome: Exploring multiple definitions of asthma across birth cohorts in the Environmental influences on Child Health Outcomes Children's Respiratory and Environmental Workgroup.

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

Identification of two early life eczema and non-eczema phenotypes with high risk for asthma development.

Background: The "atopic march" has been considered a linear progression starting with eczema and culminating with development of asthma. Not all asthma cases, however, are preceded by eczema, and not all children with eczema go on to develop asthma.

Objective: The aim of this study was to explore the impact of allergic sensitization patterns on the association between early eczema and later childhood asthma.

Environmental exposures and mechanisms in allergy and asthma development.

Environmental exposures interplay with human host factors to promote the development and progression of allergic diseases. The worldwide prevalence of allergic disease is rising as a result of complex gene-environment interactions that shape the immune system and host response. Research shows an association between the rise of allergic diseases and increasingly modern Westernized lifestyles, which are characterized by increased urbanization, time spent indoors, and antibiotic usage.

A Pediatric Asthma Risk Score to better predict asthma development in young children.

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.

Vitamin D supplementation attenuates asthma development following traffic-related particulate matter exposure.

Background: Recent literature suggests that children who are vitamin D deficient are uniquely susceptible to the effects of traffic-related air pollution (TRAP) exposure. This is highly significant because large segments of the population reside in zones of high TRAP exposure.

Objective: We sought to determine whether vitamin D supplementation mitigates the effect of TRAP exposure on asthma development, asthma exacerbation, and/or airway inflammation and to determine the timing of vitamin D supplementation that confers maximal health benefit.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.

Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis.

Ohio Pediatric Asthma Repository: Opportunities to Revise Care Practices to Decrease Time to Physiologic Readiness for Discharge.

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.

Nasal DNA methylation is associated with childhood asthma.

Aim: We aim to study DNA methylation (DNAm) variations associated with childhood asthma.

Methods: Nasal DNAm was compared between sibling pairs discordant for asthma, 29 sib pairs for genome-wide association studies and 54 sib pairs for verification by pyrosequencing. Associations of methylation with asthma symptoms, allergy and environmental exposures were evaluated.

Adjunctive Pharmacotherapies in Children With Asthma Exacerbations Requiring Continuous Albuterol Therapy: Findings From The Ohio Pediatric Asthma Repository.

Objectives: To identify associations between use of ipratropium and/or intravenous magnesium and outcomes of children hospitalized with acute asthma exacerbations and treated with continuous albuterol.

Methods: Secondary analysis of data from children prospectively enrolled in the multicenter Ohio Pediatric Asthma Repository restricted to only children who were treated with continuous albuterol in their initial inpatient location. Children were treated with adjunctive therapies per the clinical team.

Staphylococcal Biofilms in Atopic Dermatitis.

Purpose Of Review: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is a major public health burden worldwide. AD lesions are often colonized by Staphylococcus aureus and Staphylococcus epidermidis. An important aspect of Staphylococcus spp.

Nasal DNA methylation differentiates corticosteroid treatment response in pediatric asthma: A pilot study.

Background: Treatment response to systemic corticosteroid in asthmatic children is heterogeneous and may be mediated by epigenetic mechanism(s). We aim to identify DNA methylation (DNAm) changes responsive to steroid, and DNAm biomarkers that distinguish treatment response.

Materials And Methods: We followed 33 children (ages 5-18) presenting to the Emergency Department (ED) for asthma exacerbation.

Rhinovirus infection results in stronger and more persistent genomic dysregulation: Evidence for altered innate immune response in asthmatics at baseline, early in infection, and during convalescence.

Background: Rhinovirus (HRV) is associated with the large majority of virus-induced asthma exacerbations in children and young adults, but the mechanisms remain poorly defined.

Methods: Asthmatics and non-asthmatic controls were inoculated with HRV-A16, and nasal epithelial samples were obtained 7 days before, 36 hours after, and 7 days after viral inoculation. RNA was extracted and subjected to RNA-seq analysis.