An inhaled dose of budesonide induces genes involved in transcription and signaling in human airways
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83233 | GEO | 2016/06/11
SECONDARY ACCESSION(S): PRJNA325317
REPOSITORIES: GEO
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Project description:Inhaled corticosteroids (ICS) control airway inflammation in mild to moderate asthma by reducing inflammatory gene expression. However, incomplete understanding of the molecular mechanisms underpinning corticosteroid action hinders development of improved therapies for more severe disease. Microarray analysis was performed on RNA from biopsies taken from healthy individuals after receiving single dose of ICS to characterize corticosteroid-induced modulation of gene expression in the human airways. Healthy male, non-smoker, non-allergic volunteers (age 18-50 years) with normal lung function were recruited into a prospective, double-blind, placebo-controlled, randomized, two-period crossover study involving an initial screening visit, followed by two intervention visits. Participants were screened at visit 1 for fulfilment of the study eligibility criteria. At visit 2, volunteers were randomized to receive inhaled budesonide (1600 µg) or placebo, both via Turbuhaler. Two to three weeks later, at visit 3, participants received either budesonide or placebo, as appropriate to complete both study arms. Six hours after placebo or a budesonide inhalation, bronchial biopsies were obtained via bronchoscopy.
2016-06-11 | E-GEOD-83233 | biostudies-arrayexpress
Project description:Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results: AsResults: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic. a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.
2021-07-15 | GSE179156 | GEO
Project description:As part of the Taiwanese Consortium of Childhood Asthma Study (TCCAS), a new prospective sub-study was conducted to investigate the effectiveness of inhaled corticosteroids (ICS) treatment. Patients were categorized as either responders (R) or non-responders (NR), based on the improvement of their pulmonary function after ICS treatment. We analyzed the transcriptomes of asthma with ICS non-responsers and responders.
2023-04-24 | GSE230048 | GEO
Project description:The Differential Effects of Inhaled Symbicort and AdvaiR on Lung Microbiota (DISARM) study aimed to determine the effects of inhaled corticosteroids (ICS) on the lung microbiome. The full trial protocol is registered at clinicaltrials.gov (NCT02833480) and the study was approved by the Human Research Ethics Committee of the University of British Columbia and Providence Health Care (H14-02277). Participants were randomized to receive inhaled long-acting beta agonist (LABA) treatment with formoterol, or LABA/ICS combination treatment with formoterol/budesonide or salmeterol/fluticasone propionate, for 12 weeks. Bronchoscopy was performed before and after treatment, and bronchoalveolar lavage fluid and bronchial brushes (6th-8th generation) were collected. This dataset contains RNA-seq data from the bronchial brushes. RNA was extracted from cytological brush specimens stored in QIAzol RNA lysis buffer (QIAGEN, Stockach, Germany) using the RNeasy Plus kit (QIAGEN) according to the manufacturer’s instructions, and specimens were submitted for sequencing at the University of British Columbia Biomedical Research Centre. Sample quality control was performed using the Agilent 2100 Bioanalyzer (Agilent, Santa Clara, CA, USA). Qualifying samples were then prepared following the standard protocol for the NEBnext Ultra ii Stranded mRNA (New England Biolabs, Ipswich, MA, USA). Sequencing was performed on the Illumina NextSeq 500 (Illumina, San Diego, CA, USA) with paired end 42bp × 42bp reads. Samples were sequenced in batches of 24, with batches formed by random selection of samples.
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Project description:We performed genome-wide profiling of miRNA expression in the airway epithelial compartment in asthma to identify miRNA pathways associated with epithelial abnormalities using miRNA microarrays and real-time PCR. We also sought to identify the effect of inhaled corticosteroids (ICS) on airway epithelial miRNA expression
2012-12-05 | GSE34466 | GEO
Project description:We performed genome-wide profiling of miRNA expression in the airway epithelial compartment in asthma to identify miRNA pathways associated with epithelial abnormalities using miRNA microarrays and real-time PCR. We also sought to identify the effect of inhaled corticosteroids (ICS) on airway epithelial miRNA expression Samples were obtained from airway epithelial cells by bronchoscopic brushing from three groups of subjects: Healthy Controls ( N=12), Steroid Naïve Asthma (N=16), Steroid-requiring Asthma (N=19).
2012-12-05 | E-GEOD-34466 | biostudies-arrayexpress
Project description:In 2019, the Global Initiative for Asthma treatment guidelines were updated to recommend that inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) combination therapy should be a first-in-line treatment option for asthma. Although clinically superior to ICS, mechanisms underlying the efficacy of this combination therapy remain unclear. We hypothesised the existence of transcriptomic interactions, an effect that was tested in primary human bronchial epithelial cells (pHBECs) using formoterol and budesonide as representative LABA and ICS, respectively. To investigate the gene expression changes by each condition, transcriptomic analysis was performed on RNA extracted from pHBECs treated with budesonide, formoterol, or both combined.
2020-11-20 | GSE161805 | GEO
Project description:We performed small RNA sequencing (TruSeq) of gene expression on bronchial cells from human bronchial epithelial brushings from 16 independent subjects whose samples were classified as either healthy controls (with no asthma or lung disease) or steroid-naive asthmatics (subjects with asthma not using inhaled corticosteroids (ICS) for 6 weeks before enrollment that were studied at baseline ('Steroid-naive asthma - Baseline') or after 8 weeks of treatment with budesonide, 200 μg twice a day, ('Steroid-naive asthma - Post-ICS treatment')). The goal was to assess abundance of miRNAs in all the samples collectively.
2021-01-01 | GSE164119 | GEO
Project description:The heterogeneity of asthma has prompted attempts at classifications based on clinical phenotypes and cluster designations. Although helpful, reliance on clinical parameters fails to address fundamental issues resulting in specific phenotypes, in particular, steroid-resistant (SR) asthma. Limited data are available defining the mechanisms or pathways (endotypes) causing the failure of inhaled corticosteroids (ICS) in SR asthmatics. Unlike CD4+ T cells, both human and mouse CD8+ T cells fail to undergo apoptosis in the presence of corticosteroids (CS) positioning them as unique effector cells. Whole transcriptome analyses of peripheral CD8+ T cells from steroid-sensitive or steroid-resistant asthmatics or healthy controls on days 0 and 8 were performed.
2017-10-08 | GSE100624 | GEO
Project description:Inhaled allergen challenge of subjects with allergic asthma allows the study of mechanisms involved in allergen-induced airway inflammation. The objective of this study was to identify changes in the plasma proteome associated with a late phase response (LPR) causing airway obstruction occurring 4-8 hours after the initial early response. Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed. Mass spectrometry data was analyzed using a linear regression to model the relationship between the degree of airway obstruction during the LPR and plasma proteome changes evoked by the inhaled allergen challenge. Inhaled allergen challenge induced changes in the plasma proteome including upregulation of the protease inhibitors alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Out of 396 quantified proteins, 150 showed a statistically significant change 23 hours post allergen challenge. Further proteomic changes were associated with the LPR, including altered levels of coagulation factors such as an increased factor XII A and a decreased von Willebrand factor. Allergic reactions to inhaled allergens in asthmatic subjects was associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors show the largest changes, likely to influence the inflammatory response. Of several other proteins altered in relation to the LPR, many are associated with coagulation.
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