Ontology highlight
ABSTRACT:
PROVIDER: PRJNA946338 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23908702.fastq.gz | Fastqsanger.gz | |||
| SRR23908703.fastq.gz | Fastqsanger.gz | |||
| SRR23908704.fastq.gz | Fastqsanger.gz | |||
| SRR23908705.fastq.gz | Fastqsanger.gz | |||
| SRR23908706.fastq.gz | Fastqsanger.gz |
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Project description:Rationale: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia. Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, but the mechanisms of this benefit remain unclear. Objectives: To investigate the biologic effects of corticosteroids in pneumococcal pneumonia in mice and in patients Methods: We studied lower respiratory tract transcriptomes from an observational cohort of mechanically ventilated patients and from a pneumonia model in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify mechanisms of lung injury in S. pneumoniae with and without adjunctive steroid therapy. Measurement and Main Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathology lung injury score, and (5) hypoxemia, but did not increase bacterial burden. Conclusions: In combination with appropriate antibiotics in mice, treatment of pneumococcal pneumonia with steroid therapy reduces hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The concordance of transcriptional data in the mouse model and in patients with pneumococcal pneumonia supports the translational relevance of this work.
2024-06-05 | GSE246398 | GEO
Project description:Early diagnosis of acute community-acquired pneumonia (CAP) is important in patient triage and treatment decisions. To identify biomarkers that distinguish patients with CAP from non-CAP controls, we conducted an untargeted global metabolome analysis for plasma samples from142 patients with CAP (CAP cases) and 97 without CAP (non-CAP controls). Thirteen lipid metabolites could discriminate between CAP cases and non-CAP controls with area-under-the-receiver-operating-characteristic curve of > 8 (P ≤ 10-9). The levels of glycosphingolipids, sphingomyelins, lysophosphatidylcholines and L-palmitoylcarnitine were higher, while the levels of lysophosphatidylethanolamines were lower in the CAP cases than those in non-CAP controls. All 13 metabolites could distinguish CAP cases from the non-infection, extrapulmonary infection and non-CAP respiratory tract infection subgroups. The levels of trihexosylceramide (d18:1/16:0) were higher, while the levels of lysophosphatidylethanolamines were lower, in the fatal than those of non-fatal CAP cases. Our findings suggest that lipid metabolites are potential diagnostic and prognostic biomarkers for CAP.
2016-08-11 | MTBLS354 | MetaboLights
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
2021-03-03 | GSE168018 | GEO
Project description:We preformed a systems biological assessment of lower respiratory tract host immune responses and microbiome dynamics in COVD-19 patients, using bulk RNA-sequencing, single-cell RNA sequencing, and techniques, and microbiome analysis. Are focus was on differential gene expression in severe COVID-19 patients who developed ventilator associated pneumonia (VAP) during their course versus severe COVID-19 patients who did not develop VAP. We found early impairment in antibacterial immune signaling in patients two or more weeks prior to the development of VAP, compared to COVID-19 patients who did not develop VAP. There was no signficant difference in viral load, but an association of disruption in lung microbiome by alpha and beta diversity metrics was also found.
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Project description:Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy can be used as a model to safely induce transient airway inflammation in the human lung. The LPS challenge model enables investigation of cellular mechanisms involved in pulmonary inflammatory processes as well as pharmacodynamic analysis of investigational drugs for the treatment of respiratory diseases. Aim of this work was to describe the transcriptomic profile of the human segmental LPS challenge model with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage fluid (BAL) and biopsies were sampled from twenty-eight smoking, healthy subjects, followed by segmental LPS challenge and saline control challenge. Twenty-four hours post instillation, BAL and biopsies were collected from the challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced for subsequent data analysis. Differential gene expression analysis resulted in 6316 upregulated differentially expressed genes (DEGs) and 241 downregulated DEG in BAL, but only one downregulated DEG in biopsy samples after LPS challenge compared to saline challenge. Upregulated DEG in BAL were related to molecular functions such as “Inflammatory response” or “antimicrobial humoral immune response mediated by antimicrobial peptide”, enriched biological processes such as “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt signaling pathway”, “Ras signaling pathway” or “JAK-STAT signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia (CAP). Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.
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Project description:This project was a prospective translational study aimed at evaluating gene expression profiles (GEP) of patients with ventilator-associated pneumonia (VAP) . GEP of VAP were compared with a control group of patients which did not developed ventilator-associated lower respiratory tract infection despite being subjected to mechanical ventilation.
2018-01-31 | E-MTAB-5638 | biostudies-arrayexpress
Project description:Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 microbiome studies by analyzing the upper respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We found that time in the intensive care unit and the type of oxygen support explained the most variation within the upper respiratory tract microbiome, dwarfing (non-significant) effects from viral load, disease severity, and immune status. Specifically, mechanical ventilation was linked to altered community structure, lower species- and higher strain-level diversity, and significant shifts in oral taxa previously associated with COVID-19.
| EGAS00001004951 | EGA