A sputum gene expression signature of six biomarkers identifies asthma inflammatory phenotype and steroid responsiveness
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45111 | GEO | 2014/03/25
SECONDARY ACCESSION(S): PRJNA192901
REPOSITORIES: GEO
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Project description:This study identifies differentially expression genes in the sputum of people with eosinophilic, neutrophilic and paucigranulocytic asthma. A selection of markers identified using this microarray were further validated using qPCR on a wider sample set. Gene expression profiles were generated from induced sputum samples from 47 asthma patients and were grouped by the inflammatory phenotype assigned using sputum cell counts into neutrophilic asthma (n=12), eosinophilic asthma (n=17) and paucigranulocytic asthma (n=18). RNA was extracted, amplified and hybridised to Illumina Sentrix HumanRef-8 Version 2 Expression BeadChips, and genes that were differentially expressed between asthma inflammatory phenotypes were compared.
2014-03-25 | E-GEOD-45111 | biostudies-arrayexpress
Project description:We evaluated the applicability and usability of whole-genome methylomics of sputum samples in molecular profiling of chronic inflammatory lung diseases. Genomic DNA was purified from sputum samples of subjects with Asthma, COPD as well as healthy controls and analyzed on the Illumina Infinium HumanMethylation 450k platform.
2020-10-25 | GSE148000 | GEO
Project description:Asthma is a complex, chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Distinct inflammatory phenotypes of eosinophilic, mixed, neutrophilic and paucigranulocytic asthma are identified in patients, but most in vivo mouse models, studying asthma mechanisms, mimic only eosinophilic phenotype in humans. The detailed unbiased in vivo studies on molecular responses among different kinds of inflammation in asthma models are lacking. Therefore, we developed mouse models representing three different inflammatory phenotypes of airway inflammation, namely eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitisation. We used microarrays to determine the global gene expression in the lungs of mice with eosinophilic, mixed and neutrophilic inflammatory phenotypes to uncover underlying differences in clinical presentation and to find novel molecular targets and pathways, which might reflect different molecular mechanisms of the disease. By whole genome transcriptome profiling, we found that airway tight junction (TJ) molecules, mucins and inflammasome-related genes are differentially expressed in distinct phenotypes of allergic airway inflammation. Next, detailed analysis of several molecules from these families by quantitative RT-PCR, western blot and confocal microscopy revealed that (i) Zo-1 and Cldn18 were downregulated in all phenotypes, while Cldn4 upregulation was characteristic for neutrophilic airway inflammation; (ii) mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic asthma, and (iii) upregulation of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1 and IL-1b was characteristic for neutrophilic asthma. Finally, we showed that inflammasome/Th-17/neutrophilic axis cytokines, namely IL-1b and IL-17 impaired epithelial barrier function and increased mucins expressions in primary human bronchial epithelial cells from normal and asthmatic donors. Our findings suggest that differential expression of TJs, mucins and inflammasome-related molecules in distinct asthma phenotypes could be mechanistically linked and might further reflect the differences observed in the clinic.
2018-10-03 | GSE108417 | GEO
Project description:In addition to analyzing whole-genome methylation, we concomitantly evaluated sputum cell gene expression in the context of chronic inflammatory lung disease. Nucleic acids were purified from sputum samples of subjects with Asthma, COPD as well as healthy controls. Gene expression was analyzed on the Agilent Human GE 4x44k v2 platform.
2020-10-25 | GSE148004 | GEO
Project description:Gene expression profiles were generated from induced sputum samples in asthma and healthy controls. The study identified differential gene expression and pathways in severe asthma.
2019-09-12 | GSE137268 | GEO
Project description:Severe asthma is a complex disease with different inflammatory phenotypes. Transcriptomic profiling has contributed to understanding the pathogenesis of asthma, especially type-2 inflammation; however, there is still poor understanding of non-eosinophilic asthma, and consequently there are limited treatment options. The aim of this study was to determine transcriptomic profiles in endobronchial biopsies of adults with severe asthma and different inflammatory phenotypes (neutrophilic, eosinophilic and paucigranulocytic) compared with healthy controls.
2021-07-31 | GSE143303 | GEO
Project description:Background: MicroRNAs are potent regulators of biologic systems that are critical to tissue homeostasis. Individual microRNAs have been identified in airway samples. However, a systems analysis of the microRNA-mRNA networks present in the sputum that contribute to airway inflammation in asthma has not been published. Methods: We conducted a genome-wide analysis of microRNA and messenger RNA (mRNA) in the sputum from patients with asthma and correlated expression with clinical phenotypes. Weighted gene correlation network analysis (WGCNA) was implemented to identify microRNA networks (modules) that significantly correlate with clinical features of asthma and mRNA expression networks. MicroRNA expression in peripheral blood neutrophils and lymphocytes, and in situ hybridization of the sputum were used to identify the cellular sources of microRNAs. MicroRNA expression obtained before and after ozone exposure was also used to identify changes associated with neutrophil counts in the airway. Results: Six microRNA modules were associated with clinical features of asthma. A single module (nely) was associated with a history of hospitalizations, lung function impairment, and numbers of neutrophils and lymphocytes in the sputum. Of the 12 microRNAs in the nely module, hsa-miR-223-3p was the highest expressed microRNA in neutrophils and was associated with increased neutrophil counts in the sputum in response to ozone exposure. Multiple microRNAs in the nely module correlated with two mRNA modules enriched for toll-like receptor (TLR) and Th17 signaling, and endoplasmic reticulum stress. Hsa-miR-223-3p was a key regulator of the TLR and Th17 pathways in the sputum of subjects with asthma. Conclusions: This study of sputum microRNA and mRNA expression from patients with asthma demonstrates the existence of microRNA networks and genes that are associated with features of asthma severity. Among these, hsa-miR-223-3p, a neutrophil-derived microRNA, regulates TLR/Th17 signaling and endoplasmic reticulum stress.
2020-03-04 | GSE146306 | GEO
Project description:Cystic fibrosis (CF) is an inherited, multi-system disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a ubiquitous ion channel important for epithelial hydration. A direct consequence of this dysfunction is impaired mucociliary clearance, chronic airway infection and a persistent neutrophilic inflammatory response that results in progressive loss of lung function, development of respiratory failure and premature death. Partial restoration of CFTR function is now possible for most CF patients through mutation specific CFTR modulators. Ivacaftor monotherapy produces significant clinical improvement in CF patients with the G511D mutation. Dual therapy, combining ivacaftor with lumacaftor or tezacaftor, results in modest clinical improvements in patients homozygous for F508del. More recently, triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic improvements in lung function and quality of life in patients homozygous and heterozygous for F508del. Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms by interrogating the proteome, an entire set of proteins within biological samples. It has confirmed the central role of neutrophilic immune dysregulation in CF and non-CF bronchiectasis, particularly involving the release of antimicrobial proteins and neutrophil-extracellular traps (NETs), and through impaired anti-inflammatory mechanisms. These processes produce distinct molecular signatures within the sputum proteome that become increasingly abnormal with chronic airway infection and progressive lung disease severity. In CF patients, airway and systemic inflammatory cytokines potentially related to these signatures reduce with the various forms of CFTR modulation. To date, no studies of ETI therapy in CF lung disease have assessed large-scale change in protein expression using untargeted proteomics. We hypothesised that ETI therapy would shift the sputum proteome toward health, potentially normalising airway biology in people with CF. The objectives of this study were to investigate changes in the CF sputum proteome with the introduction of ETI, correlate these with changes in clinical markers of disease severity, and make comparisons with the sputum proteome in healthy controls and in repeat samples from CF patients not suitable for ETI therapy. We also explored which molecular pathways associated with CF lung disease did not change with ETI.
2023-11-14 | PXD041950 | Pride
Project description:A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma
| PRJNA610081 | ENA
Project description:Background: Macrophages are important cells in pathogenesis of obstructive lung diseases including asthma and chronic obstructive pulmonary disease (COPD). The aim of the study was a multivariate, genetic, comparative analysis of macrophages from patients with asthma and COPD. Methods: Macrophages were isolated from induced sputum (IS) by magnetic bead separation. Transcriptomic measurements were carried out using Affymetrix Human Gene 2.1 ST ArrayStrip in 17 samples: 8 asthma (4 ICS naive , 4 ICS treated), 4 COPD and 5 control samples. The expression of the most significantly differentiating genes was evaluated by real time PCR in 34 samples (15 patients with asthma, 11 patients with COPD and 17 controls). Results: USP53 was the only gene differentially expressed (p adjusted clue =0.09) in the comparison between ICS naïve and ICS treated asthma. The PCR verification showed increased expression of BTF3, CDS2, DNAJC13, DDX5, GNAI2, SCGB1A1, SIRPB1, TRAF3IP, USP53, WDR49 in the asthma compared to COPD group. The changed gene expression profile of macrophages were characterized mostly by gene ontology terms linked with cell motility, cilium function, cell junction and adhesion organization. Conclusions: Gene expression profiling of sputum macrophages revealed distinct molecular capacity in asthma and COPD. The role of sputum macrophages in the pathophysiology of obstructive lung diseases is probably connected with biological processes associated with their motility, cilium dysfunction and cell junction organization.
2018-08-09 | GSE112260 | GEO