National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Asthma & T cell. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease

Abstract: Objectives Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the s chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case–control study assessed the contribution of genetics and exposure in the development of BeS and CBD. Methods Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers’ job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity. Results Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS. Conclusions Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.

Nascent RNA sequencing defines dynamic aryl hydrocarbon receptor signaling responses to wood smoke particles

Abstract: Transcriptional responses to wildfire smoke, an increasingly important cause of human morbidity, are poorly understood. Here, using a combination of precision nuclear run-on sequencing (PRO-seq) and the assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify rapid and dynamic changes in transcription and chromatin structure in Beas-2B airway epithelial cells after exposure to wood smoke particles (WSP). By comparing 30 and 120 minutes of WSP exposure, we defined three distinct temporal patterns of transcriptional induction and chromatin responses to WSP. Whereas transcription of canonical targets of the aryl hydrocarbon receptor (AHR), such as CYP1A1 and AHRR, was robustly increased after 30 minutes of WSP exposure, transcription of these genes and associated enhancers returned to near baseline at 120 minutes. ChIP-qPCR assays and AHR knockdown confirmed a role for AHR in regulating these transcriptional responses, and we applied bioinformatics approaches to identify novel AHR-regulated pathways and targets including the DNA methyltransferase, DNMT3L, and its interacting factor, SPOCD1. Our analysis also defined a role for NFkB as a primary transcriptional effector of WSP-induced changes in gene expression. The kinetics of AHR- and NFkB-regulated responses to WSP were distinguishable based on the timing of both transcriptional responses and chromatin remodeling, with induction of several cytokines implicated in maintaining the NFkB response. In aggregate, our data establish a direct and primary role for AHR in mediating airway epithelial responses to WSP and identify crosstalk between AHR and NFkB signaling in controlling pro-inflammatory gene expression.

Commentary: Psychological and Behavioral Challenges for Families of Children with Eosinophilic Gastrointestinal Disorders

Abstract: The current issue of the Journal of Pediatric Psychology includes two papers about children and adolescents with eosinophilic gastrointestinal diseases, or EGIDs. Each paper addresses key behavioral and psychological aspects of pediatric EGIDs. The first paper, by Taft and colleagues, characterizes caregiver stress in the parents of children with EGIDs and describes the relationships between the caregivers’ pediatric illness stress experiences and their own psychological functioning, as well as their children’s behavioral adjustment (Taft, Ballou, & Keefer, 2012). The second paper, by Hommel and colleagues, examines treatment adherence rates for children with EGIDs and their families (Hommel, Franciosi, Hente, Ahrens, & Rothenberg, 2011). Together, the papers provide an initial look at this recently recognized disease in terms of the challenges posed for the caregivers of the children with EGIDs, and to some extent for the children themselves, as they strive to cope with the illnesses and follow the recommended treatments aimed at disease management. The goal here is to underscore the importance of certain aspects of the initial findings from the papers and to further describe disease characteristics and related impacts that must be considered in future research regarding behavioral and psychological aspects of pediatric EGIDs. The paper by Taft and colleagues focuses on caregiver stress that is experienced by mothers of children with EGIDs, mostly with eosinophilic esophagitis (EoE). In comparison with parent stress levels measured with the same instrument in other studies of pediatric illness (e.g., Hilliard, Monaghan, Cogen, & Streisand, 2010), stress levels for caregivers in this study were extraordinarily high. Demographic correlates of the high caregiver stress levels, low socioeconomic status and single parenting, may reflect reduced resources and support for meeting medical care demands for these children. Caregiver stress was also associated with disease variables including symptoms and disease management burden. In the Taft study, symptom burden was measured using mothers’ ratings of ‘‘recent flare severity.’’ For EoE, the maternal response to a ‘‘recent flare’’ not only includes an assessment of severity of the child’s symptoms, but also an attempt to determine how the symptom might be associated with a particular food exposure. This determination is especially challenging because most eosinophilic inflammation results from non-immunoglobulin E (IgE)-mediated allergic processes, with delayed responses that evolve over hours and days following food allergen exposure (Atkins, Kramer, Capocelli, Lovell, & Furuta, 2009), clouding the identification of culprit foods. Many children with EoE also have IgE-mediated food allergies, with symptoms that occur immediately after ingestion and have potential for life threatening anaphylaxis. Distinguishing between IgE-mediated and non-IgE-mediated food allergies may be critical for understanding caregiver anxiety and children’s distress regarding dietary restrictions and accidental food exposure. Certain qualitative aspects of EGID symptoms also can be associated with heightened caregiver stress. For EoE, the most commonly diagnosed of the EGIDs, presenting symptoms vary according to patient age. For example, feeding dysfunction is the most common primary presenting symptom for very young children (Mukkada et al., 2010). Epidemiological studies have shown that as many as a third of children diagnosed with EoE are less than 3–5 years of age, so studies of pediatric patients that encompass the entire age range from 0 to 18 years likely include a substantial proportion of young children with feeding problems. Having a young child with food refusal or vomiting, often resulting in poor weight gain or failure to thrive, elicits high anxiety, and is extraordinarily distressing for parents. Abdominal pain is the most common presenting symptom for older children; the ambiguity of this complaint, often lacking validating external evidence (unlike