Multidimensional Assessment of the Host Response in Mechanically Ventilated Patients with Suspected Pneumonia
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ABSTRACT:
PROVIDER: PRJNA498689 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8114470.fastq.gz | Fastqsanger.gz | |||
| SRR8114471.fastq.gz | Fastqsanger.gz | |||
| SRR8114464.fastq.gz | Fastqsanger.gz | |||
| SRR8114465.fastq.gz | Fastqsanger.gz | |||
| SRR8114466.fastq.gz | Fastqsanger.gz |
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Project description:Rationale: Patients in the intensive care unit (ICU) are frequently exposed to unnecessary antibiotics. Markers of the host response to infection may aid pneumonia diagnosis and avoid antibiotic-induced complications. Objective: To assess the host response to suspected bacterial pneumonia through assessment of alveolar neutrophilia and transcriptomic profiling of alveolar macrophages. Methods: We determined the test characteristics of BAL neutrophilia for the diagnosis of bacterial pneumonia in 3 cohorts of mechanically ventilated patients. In one cohort, we also isolated alveolar macrophages from BAL fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: BAL neutrophilia was highly sensitive for bacterial pneumonia in both the retrospective (N = 851) and validation cohorts (N = 76 and N = 79) with a negative predictive value of over 90% when BAL neutrophil percentage was less than 50%. A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to BAL neutrophilia. Conclusions: A BAL neutrophil percentage of less than 50% is highly sensitive for bacterial pneumonia. Informative transcriptomic signatures can be generated from BAL fluid obtained during routine clinical care in the ICU. The identification of novel host response biomarkers is a promising approach to aid the diagnosis and treatment of pneumonia.
2018-11-06 | GSE121871 | GEO
Project description:This project focuses both on the separate and combined effects of large tidal volume ventilation and hyperoxia on gene expression in the lungs of anesthetized rats. Rats were either mechanically or spontaneously ventilated at either 21 or 100% oxygen and expression levels were evaluated on RG_U34 GeneChips.
2007-10-10 | E-GEOD-489 | biostudies-arrayexpress
Project description:microRNA expression in bronchoalveolar lavage fluid from mechanically ventilated patients with cardiogenic shock
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Project description:Purpose: ATAC-seq was performed on preterm lambs that were ventilated by invasive mechanical ventilation or noninvasive respiratory support utilizing a mask and compared to gestation-age-matched preterm lambs that were not ventilated and naturally delivered term lambs. Methods: Lung chromatin access profiles were generated for: 1) Unventilated preterm lamb, 2) preterm lambs delivered at gd131 and intubated and mechanically ventilated for 3 days, 3) preterm lambs delivered at gd131 and not intubated and resuscitated by placing a face mask over the nose and mouth and controlling O2 delivery via a computer-controlled electronic blower device, 4) unventilated naturally delivered full-term lambs. Results: Using an optimized data analysis workflow, we mapped between 76 and 96 million sequence reads per sample to the sheep genome Conclusions: Our study represents the first detailed analysis of ventilated preterm lung chromatin access, with biologic replicates, generated by ATAC-seq
2021-06-30 | GSE163807 | GEO
Project description:Rationale: Overstretching of lung parenchyma may lead to tissue injury, especially during mechanical ventilation. There are no specific biomarkers of lung stretch. Objectives: To identify transcriptomic signatures of micro-RNAs and genes specifically related to lung stretch and validate them in preclinical models. Methods: Data on micro-RNA expression in response to stretch in experimental models were systematically pooled. Signatures were identified as those micro-RNAs or genes with differential expression in samples from stretched cells, and optimized using a greedy algorithm. Transcriptomic scores were calculated as the difference of geometric means in expression of up- and down-regulated features, and compared among different magnitudes of stretch. The accuracy of these scores was validated in animal models of lung injury, ex vivo mechanically ventilated human lungs and in bronchoalveolar lavage fluid (BALF) from patients under different ventilatory conditions. Measurements and main results: Eight micro-RNAs were differentially expressed in stretched cell cultures (n=24). Amongst the genes regulated by these micro-RNAs, a 180-gene signature was identified in ex vivo models (n=106) and refined using data from animal models (n=143) to obtain a 4-gene signature. The corresponding scores were significantly higher in samples submitted to stretch or injurious mechanical ventilation. The microRNA signatures were validated in human tissue and BALF, with areas under the ROC curve between 0.89 and 1 respectively to identify lung overdistention. Conclusions: Lung cell stretch induces the expression of specific micro-RNA and genes. These signatures may be used to obtain an index of lung overstretching that can be measured at the bedside.
2025-05-01 | GSE197752 | GEO
Project description:Purpose: The goal of this study was to measure by RNA-seq the impact of preterm birth and invasive mechanical ventilation verses noninvasive respiratory support on the lung transcriptome Methods: Lung mRNA profiles were generated for: 1) Unventilated preterm lamb, 2) preterm lambs delivered at gd131 and intubated and mechanically ventilated for 3 days, 3) preterm lambs delivered at gd131 and not intubated and resuscitated by placing a face mask over the nose and mouth and controlling O2 delivery via a computer-controlled electronic blower device, 4) unventilated naturally delivered full-term lambs. Results: Using an optimized data analysis workflow, we mapped between 61 and 81 million sequence reads per sample to the sheep genome Oar_v3.1/oviAri3 Conclusions: Our study represents the first detailed analysis of ventilated preterm lung transcriptomes, with biologic replicates, generated by RNA-seq
2021-06-30 | GSE163806 | GEO
Project description:In critically ill patients, the development of pneumonia results in significant morbidity and mortality and additional health care costs. The accurate and rapid identification of the microbial pathogens in patients with pulmonary infections might lead to targeted antimicrobial therapy with potentially fewer adverse effects and lower costs. Major advances in next-generation sequencing (NGS) allow culture-independent identification of pathogens. The present study used NGS of essentially full-length PCR-amplified 16S ribosomal DNA from the bronchial aspirates of intubated patients with suspected pneumonia. The results from 61 patients demonstrated that sufficient DNA was obtained from 72% of samples, 44% of which (27 samples) yielded PCR amplimers suitable for NGS. Out of the 27 sequenced samples, only 20 had bacterial culture growth, while the microbiological and NGS identification of bacteria coincided in 17 (85%) of these samples. Despite the lack of bacterial growth in 7 samples that yielded amplimers and were sequenced, the NGS identified a number of bacterial species in these samples. Overall, a significant diversity of bacterial species was identified from the same genus as the predominant cultured pathogens. The numbers of NGS-identifiable bacterial genera were consistently higher than identified by standard microbiological methods. As technical advances reduce the processing and sequencing times, NGS-based methods will ultimately be able to provide clinicians with rapid, precise, culture-independent identification of bacterial, fungal, and viral pathogens and their antimicrobial sensitivity profiles.
| S-EPMC4313225 | biostudies-literature
Project description:E. coli pneumonia isolates retrieved from mechanically ventilated patients in French ICUs.
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Project description:PurposeLiberal use of oxygen may contribute to secondary brain injury in patients with hypoxic-ischaemic encephalopathy (HIE). However, there are limited data on the effect of different oxygen regimens on survival and neurological disability in HIE patients.MethodsWe undertook a post-hoc analysis of the 166 patients with suspected HIE enrolled in a trial comparing conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary endpoint for the current analysis was death or unfavourable neurological outcome at day 180. Key secondary outcomes were day 180 mortality, and cause-specific mortality.ResultsPatients with HIE allocated to conservative oxygen spent less time in the ICU with an SpO2 ≥ 97% (26 h [interquartile range (IQR) 13-45 vs. 35 h [IQR 19-70], absolute difference, 9 h; 95% CI - 21.4 to 3.4). A total of 43 of 78 patients (55.1%) assigned to conservative oxygen and 49 of 72 patients (68.1%) assigned to usual oxygen died or had an unfavourable neurological outcome at day 180; odds ratio 0.58; 95% CI 0.3-1.12; P = 0.1 adjusted odds ratio 0.54; 95% CI 0.23-1.26; P = 0.15. A total of 37 of 86 patients (43%) assigned to conservative oxygen and 46 of 78 (59%) assigned to usual oxygen had died by day 180; odds ratio 0.53; 95% CI 0.28-0.98; P = 0.04; adjusted odds ratio 0.56; 95% CI 0.25-1.23; P = 0.15. Cause-specific mortality was similar by treatment group.ConclusionsConservative oxygen therapy was not associated with a statistically significant reduction in death or unfavourable neurological outcomes at day 180. The potential for important benefit or harm from conservative oxygen therapy in HIE patients is not excluded by these data.
| S-EPMC7431900 | biostudies-literature
Project description:We compared differential gene expression in tracheal aspirates collected mechanically ventilated subjects with COVID-19 ARDS to gene expression in tracheal aspirates from: 1) subjects with ARDS from other casues and 2) mechanically ventilated controls without evidence of pulmonary disease.
2020-12-18 | GSE163426 | GEO