PhD Defence Nanon Francine Leonie Heijnen

Keywords: ARDS (Acute respiratory distress syndrome), Precision medicine, Phenotypes, Biomarkers  
 

"Should We Lump or Split Acute Respiratory Distress Syndrome? A Biological Perspective"
 

Acute respiratory distress syndrome (ARDS) is a life-threatening type of acute inflammatory lung injury, which can only be treated with optimized supportive therapy. It affects 23% of all ventilated patients and has a high mortality of approximately 30-40%. Unfortunately, no pharmacological therapies have been identified with beneficial effects for ARDS patients. Heterogeneity in ARDS has been hypothesized as contributing factor to the failure to identify new beneficial pharmacological therapies. This thesis focused on whether ARDS patients should be lumped or split based on biological characteristics.  

In conclusion, this thesis showed that currently ARDS patients cannot be lumped based on biological characteristics. Exhaled breath biomarkers and plasma biomarkers reflecting endothelial dysfunction, alveolar injury, and inflammatory response fail to yield a highly accurate biological signature for the diagnosis of ARDS. However, biological characteristics could be used for splitting the ARDS population to reduce the heterogeneity using subphenotypes informed by biological information and associated with prognostic and predictive enrichment. 

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