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Ontology highlight
ABSTRACT:
PROVIDER: PRJEB25616 | ENA |
REPOSITORIES: ENA
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Project description:Childhood asthma is a complex disease historically defined by partially overlapping clinical features, including recurrent respiratory symptoms and reversible airway obstruction. However, the heterogeneity observed in clinical disease and airway pathology suggests that the “traditionally” defined asthma population is composed of multiple subgroups (i.e., endotypes), each with a distinct pathogenesis. Gene expression profiling of bronchial airway brushings identified the type 2-high asthma endotype, defined by excessive airway inflammation driven by type 2 cytokines, which was found in ~50% of subjects. Importantly, response to inhaled corticosteroid treatment was limited to this type 2-high endotype. The clinical utility of type 2-high asthma endotyping and the discovery of other endotypes have been limited by the need to perform an invasive bronchoscopy to obtain the bronchial brushings for analysis. Moreover, research bronchoscopies cannot be performed in children. Less invasive methods for the identification of asthma endotypes are needed. To this end, we found that the type 2-high asthma endotype can be identified by gene expression profiling of minimally invasive nasal airway epithelium brushings. Moreover, we found high nasal expression of the type 2 cytokine, IL-13,4 was associated with higher risk of asthma exacerbations among Puerto Ricans, who have the highest asthma morbidity and mortality in the U.S. Herein, we propose to use whole transcriptome sequencing of nasal airway epithelial brushings from Puerto Rican children with asthma to identify the type 2-high and other asthma endotypes, which relate to severity and drug response.
2020-07-13 | GSE152004 | GEO
Project description:Although the nose, as a gateway for organism-environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. Deep nasopharyngeal swab specimens, nasal epithelial spheroid cultures (NAEsp), and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n=146), 16 S-rRNA gene amplicon sequencing (n=64), proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH (WH to AB: p=0.005; WH to HC: p=0.021), whereas Firmicutes and Bacterioidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs (PermANOVA p=0.005). Moreover, Staphylococcaceae (p<0.05), Enterobacteriaceae (p<0.05), Burkholderiaceae (p<0.05), Xanthobacteraceae (p<0.05), and Sphingomonadaceae (p<0.05) were significantly more abundant in AB compared to WH and HC. The α‐diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB. The NAEsp bacterial exposure with M. catarrhalis, S. aureus and H. influenzae experiments provided a disrupted epithelial cell integrity, a cytokine release and cohort specific proteomic differences especially for M. catarrhalis cultures. Our comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
2021-05-27 | PXD024694 | Pride
Project description:To investigate mechanisms underlying frequent asthma exacerbation, we profiled the nasal transcriptome of both frequent and non-frequent asthma exacerbators.
2023-10-17 | GSE211158 | GEO
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. We thus hypothesis that asthmatic BSM cells could act on bronchial epithelium and modified its response to rhinovirus infection.
2023-05-02 | PXD015604 | Pride
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. Thus, we hypothesis that asthmatic BSM cell metabolism is modified compare to that of non-asthmatic and that could be a potential target to reduce asthmatic BSM cell proliferation and remodeling in asthma.
2021-06-10 | PXD015566 | Pride
Project description:Nasal swab specimens were collected from children who presented to the emergency department with an acute exacerbation of asthma or wheeze. Samples were also collected from control subjects. Convalescent/quiescent samples were collected from children who were followed-up at least 6 weeks after an acute exacerbation of asthma or wheeze. Gene expression was profiled on microarrays.
2019-02-17 | GSE103166 | GEO
Project description:Background: Nasal epithelia are emerging as a proxy measure of gene expression of the airway epithelium in asthma. We hypothesized that epigenetic marks regulate gene expression of the nasal epithelia and consequently may provide a novel target for allergic asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma [N=36] versus healthy controls [N=36]. Results were validated in an independent population of asthmatics [N=30]. Results: We identified 186 genes with significant methylation changes, either as regions (differentially methylated regions [DMRs]) or single CpGs (differentially methylated probes [DMPs]) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. The methylation changes are large (median 9.5%, range: 2.6-29.5% methylation change) and similar in magnitude to those observed in malignancies. Hypo- and hyper-methylated genes were associated with increased and decreased gene expression respectively (P<2.8x10-6 for DMRs and P<7.8x10-10 for DMPs). Quantitative analysis of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma. Conclusions: Our findings that epigenetic marks in respiratory epithelia are associated with allergic asthma in inner-city children provide new targets for biomarker development, and novel approaches to understanding disease pathogenesis. case control design with nasal epithelial cells from 36 atopic asthmatic and 36 nonatopic nonasthmatic children from the inner city
2015-11-01 | E-GEOD-65163 | biostudies-arrayexpress
Project description:The goal of this investigation was to establish proof of concept that nasal epithelium can be used as a proxy for the airway epithelium in studies of allergic asthma. We collected PBMCs, nasal epithelia, and bronchial epithelia from 12 subjects with allergic asthma and 12 control subjects without asthma, all non-Hispanic white nonsmoker adults. We conclude that genomic profiling of nasal epithelia captures most disease-relevant changes identified in airway epithelia but also provides additional targets that are most likely influenced by exposures. Thus, epigenetic marks in nasal epithelia may prove useful as a biomarker of disease severity and response to treatment or as a biosensor of the environment in asthma.
2017-10-02 | GSE104471 | GEO
Project description:The goal of this investigation was to establish proof of concept that nasal epithelium can be used as a proxy for the airway epithelium in studies of allergic asthma. We collected PBMCs, nasal epithelia, and bronchial epithelia from 12 subjects with allergic asthma and 12 control subjects without asthma, all non-Hispanic white nonsmoker adults. We conclude that genomic profiling of nasal epithelia captures most disease-relevant changes identified in airway epithelia but also provides additional targets that are most likely influenced by exposures. Thus, epigenetic marks in nasal epithelia may prove useful as a biomarker of disease severity and response to treatment or as a biosensor of the environment in asthma.
2017-10-02 | GSE104468 | GEO