Endotype of allergic asthma with airway obstruction in urban children

Multi-omics colocalization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus

“…In the first dataset, we looked for overlap between our results and cis-eQTLs and -meQTLs for genes at asthma GWAS loci in ex vivo nasal epithelial cells from 477 Puerto Rican children described by Kim et al [66]. In the second dataset, we compared our results to unpublished eQTLs and meQTLs in ex vivo nasal epithelial cells from 11-year-old children in the Urban Environment and Childhood Asthma (URECA) birth cohort study [67].…”

“…To replicate the molecular QTLs in cultured AECs in our study, we utilized two data sets with eQTL and meQTL studies in ex vivo nasal epithelial cells (see Additional file 11). One data set was generated in 477 Puerto Rican children [66] and one data set was generated in > 246 children who were ~75% African American, ~17% Hispanic, and ~7% other ancestries [67]. The details of these studies are described in Additional file 11.…”

Heterogeneity in allergic rhinitis: Explained by inducible mechanistic traits?

“…Furthermore, several inflammatory characteristics that mirror immune cell features described in asthma pathogenesis were found. For example, increased gene expression of asthma signature genes described by Altman et al 5 as representing ''NK/asthma'' was correlated with gene signatures for NK cells and effector CD8 (CD8 EM ) T cells. Indeed, pathogenic CD8 T cells have been described in severe asthma, as CD8 T cells are more insensitive to corticosteroids than are CD4 T cells and they can also produce type 2 cytokines such as IL-5 and IL-13.…”

MUCing up the airway in asthma

“…3 Although MUC5AC protects the airway from harmful environmental antigens, epithelial cell tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma, causing mucostasis and mucus plugs, thus contributing to airway obstruction. 4 Very recently, Altman et al 5 queried data from the Urban Environment and Childhood Asthma (URECA) birth cohort study to determine genetic and environmental factors that were associated with asthma severity. The URECA birth cohort is composed of children in urban areas in the United States (Baltimore, Boston, New York, and St Louis) with high rates of poverty.…”

“…The authors conjectured that ''our findings in the URECA birth cohort suggest that allergic sensitization and frequent viral wheezing episodes in early life, which are characteristic of HW-HA-LF, could promote long-term overexpression of MUC5AC and, in turn, lead to progressive airway obstruction.'' 5 In this issue of the Journal of Allergy and Clinical Immunology, Altman et al performed quantitative locus analysis of the MUC5AC gene expression in nasal epithelial cells and hypothesized that MUC5AC genotypes differentially regulate the expression of this gene in the airway, specifically in the course of an acute asthma exacerbation. 6 Using the URECA cohort, they obtained RNA-sequencing data from the nasal airway epithelial cells and then performed expressive quantitative tract loci (eQTL) and allelic-specific expression and found that there were 2 distinct groups of genetic polymorphisms of MUC5AC that independently related to the expression of this gene.…”