Abstract
Significance: Acute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. Recent Advances: The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Critical Issues: Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future Directions: Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients via molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1027-1052 |
| Number of pages | 26 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 31 |
| Issue number | 14 |
| DOIs | |
| State | Published - Nov 10 2019 |
Fingerprint
Keywords
- acute respiratory distress syndrome (ARDS)
- ARDS mortality
- candidate gene studies
- genome-wide association studies (GWAS)
- inflammation
- pathway analysis
- reactive oxygen species (ROS)
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Molecular Biology
- Clinical Biochemistry
- Cell Biology
Cite this
Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality. / Lynn, Heather; Sun, Xiaoguang; Casanova, Nancy; Gonzales-Garay, Manuel; Bime, Christian; Garcia, Joe G.N.
In: Antioxidants and Redox Signaling, Vol. 31, No. 14, 10.11.2019, p. 1027-1052.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality
AU - Lynn, Heather
AU - Sun, Xiaoguang
AU - Casanova, Nancy
AU - Gonzales-Garay, Manuel
AU - Bime, Christian
AU - Garcia, Joe G.N.
PY - 2019/11/10
Y1 - 2019/11/10
N2 - Significance: Acute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. Recent Advances: The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Critical Issues: Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future Directions: Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients via molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.
AB - Significance: Acute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. Recent Advances: The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Critical Issues: Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future Directions: Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients via molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.
KW - acute respiratory distress syndrome (ARDS)
KW - ARDS mortality
KW - candidate gene studies
KW - genome-wide association studies (GWAS)
KW - inflammation
KW - pathway analysis
KW - reactive oxygen species (ROS)
UR - http://www.scopus.com/inward/record.url?scp=85072945686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072945686&partnerID=8YFLogxK
U2 - 10.1089/ars.2018.7701
DO - 10.1089/ars.2018.7701
M3 - Review article
C2 - 31016989
AN - SCOPUS:85072945686
VL - 31
SP - 1027
EP - 1052
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 14
ER -