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Series GSE116560 Query DataSets for GSE116560
Status Public on Mar 31, 2019
Title Alveolar Macrophage Transcriptional Programs are Associated with Ventilator-Free Days in Acute Respiratory Distress Syndrome
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AMs) in patients with acute respiratory distress syndrome (ARDS) could identify dynamic biologic processes that are associated with clinical outcomes.
Objectives: To identify associations between AM transcriptional programs and the composite endpoint of ventilator-free days (VFDs) over the course of ARDS.
Methods: We performed unbiased genome-wide transcriptional profiling of AMs purified from bronchoalveolar lavage fluid collected from patients with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset. We assessed pathway enrichment in subjects with VFDs > 0 (VFD-Extubated/Alive) versus VFDs = 0 (VFD-Intubated/Dead) at each time point.
Measurements and Main Results: We found highly divergent AM transcriptional patterns at all time points between ARDS patients based on their VFD status (FDR < 0.05). “M1-like” and pro-inflammatory gene sets such as IL-6-JAK-STAT signaling were significantly enriched in AMs isolated on Day 1 in VFD-Extubated/Alive versus VFD-Intubated/Dead subjects. In contrast, many of these same gene sets were associated with the VFD-Intubated/Dead subjects on Day 8. In patients who had samples from each time point, we identified multiple AM gene clusters whose temporal expression patterns were associated with VFD status. The relationship between AM expression profiles and VFDs was distinct in subjects with Direct (pulmonary) versus Indirect (extrapulmonary) ARDS.
Conclusion: Clinically meaningful outcomes over the course of ARDS are associated with highly distinct AM transcriptional programs. Our findings suggest that interventions targeting the alveolar immune response should be tested within strictly defined time periods.
 
Overall design Total RNA from human alveolar macrophages was isolated and hybridized to Illumina HumanRef-8 BeadChips (n = 68 samples from 35 subjects).
 
Contributor(s) Gharib SA, Morrell ED
Citation(s) 30990758
Submission date Jul 02, 2018
Last update date Oct 19, 2022
Contact name Sina Gharib
E-mail(s) sagharib@uw.edu
Organization name University of Washington
Department Medicine
Street address 850 Republican St.
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL6883 Illumina HumanRef-8 v3.0 expression beadchip
Samples (68)
GSM3242812 Human AM from ARDS day 1 [AM_B1_1]
GSM3242813 Human AM from ARDS day 1 [AM_B1_10]
GSM3242814 Human AM from ARDS day 1 [AM_B1_11]
Relations
BioProject PRJNA479383

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE116560_RAW.tar 3.9 Mb (http)(custom) TAR
GSE116560_non-normalized.txt.gz 6.0 Mb (ftp)(http) TXT
Processed data included within Sample table

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