Proteomic study of acute respiratory distress syndrome: current knowledge and implications for drug development

Abstract

The acute respiratory distress syndrome (ARDS) is a common cause of acute respiratory failure, and is associated with substantial mortality and morbidity. Dozens of clinical trials targeting ARDS have failed, with no drug specifically targeting lung injury in widespread clinical use. Thus, the need for drug development in ARDS is great. Targeted proteomic studies in ARDS have identified many key pathways in the disease, including inflammation, epithelial injury, endothelial injury or activation, and disordered coagulation and repair. Recent studies reveal the potential for proteomic changes to identify novel subphenotypes of ARDS patients who may be most likely to respond to therapy and could thus be targeted for enrollment in clinical trials. Nontargeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in the disease. Proteomics will play an important role in phenotyping of patients and developing novel therapies for ARDS in the future.

Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset

“…ARDS; metabolomics; endotype; pulmonary edema; phenotype ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) remains a major medical problem in critical care, with recent estimates that 10% of ventilated patients develop ARDS and mortality rates as high as 40% for patients with severe ARDS (2). Despite more than 50 therapeutic clinical trials to date in ARDS, a dedicated drug to treat ARDS is still lacking, and mortality remains high (10).…”

Protein microarray technology: Assisting personalized medicine in oncology (Review)

“…In lung tissue, as well as in biological fluids, several proteins have been found to be overexpressed, such as apolipoprotein A1, hemoglobin α and hemoglobin β (93), osteopontin, matrix metalloproteinase (MMP)7, CXCL7, chemokine (C-X-C motif) ligand 7 (CXCL7), chemokine (C-C motif) ligand 18 (CCL18) and eosinophil-and neutrophil-derived proteins (94). However, there are still no validated markers available for subclassifying patients (92,95,96). Therefore, subgroups of patients displaying particular molecular and clinical parameters could be identified using integrative omics data that will be required to accelerate personalized medicine upcoming in pulmonary diseases (97).…”

Using omics approaches to understand pulmonary diseases

“…Proteomics studies have been conducted to find biomarkers for ARDS, and poor outcomes among those who develop it, as the need for drug development and understanding disease pathobiology are particularly high for this disease [ 167 ]. Although some pathways have been identified via these studies (e.g., inflammation and epithelial injury), ARDS-specific markers have not yet been identified [ 167 ].…”

“…Proteomics studies have been conducted to find biomarkers for ARDS, and poor outcomes among those who develop it, as the need for drug development and understanding disease pathobiology are particularly high for this disease [ 167 ]. Although some pathways have been identified via these studies (e.g., inflammation and epithelial injury), ARDS-specific markers have not yet been identified [ 167 ]. Proteomic changes in lung tissue, nasal lavage fluid and bronchoalveolar lavage fluid from patients with IPF compared to healthy controls include differences in apolipoprotein A1, hemoglobin α, and hemoglobin β [ 168 ], pulmonary fibrosis mediators (osteopontin, MMP7, CXCL7, CCL18) and eosinophil- and neutrophil-derived proteins [ 169 ].…”