Abstract
Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the high mortality associated with the disease. Despite a significant progress in the treatment of ARDS, our ability to identify early patients and predict outcomes remains limited. The development of novel biomarkers is crucial. In this study, we profiled microRNA (miRNA) expression of plasma-derived exosomes in ARDS disease by small RNA sequencing. Sequencing of 8 ARDS patients and 10 healthy subjects (HSs) allowed to identify 12 differentially expressed exosomal miRNAs (adjusted p < 0.05). Pathway analysis of their predicted targets revealed enrichment in several biological processes in agreement with ARDS pathophysiology, such as inflammation, immune cell activation, and fibrosis. By quantitative RT-PCR, we validated the alteration of nine exosomal miRNAs in an independent cohort of 15 ARDS patients and 20 HSs, among which seven present high capability in discriminating ARDS patients from HSs (area under the curve > 0.8) (miR-130a-3p, miR-221-3p, miR-24-3p, miR-98-3p, Let-7d-3p, miR-1273a, and miR-193a-5p). These findings highlight exosomal miRNA dysregulation in the plasma of ARDS patients which provide promising diagnostic biomarkers and open new perspectives for the development of therapeutics.
Highlights
Acute respiratory distress syndrome (ARDS) is a heterogeneous entity associating clinical, radiological, and pathological features leading to a severe decrease in lung diffusing capacity and compliance (Ashbaugh et al, 1967)
ARDS is characterized by diffuse alveolar damage (DAD), associated with an increase in alveolar and capillary permeability resulting in an interstitial and alveolar edema that requires mechanical ventilation (Katzenstein et al, 1976; Mendez and Hubmayr, 2005; Cardinal-Fernández et al, 2017)
The prevalence is variable according to epidemiological studies but could reach up to 10.4% in patients admitted to the intensive care unit for a mortality of around 50% in the subgroup of patients suffering from severe ARDS (Bellani et al, 2016)
Summary
Acute respiratory distress syndrome (ARDS) is a heterogeneous entity associating clinical, radiological, and pathological features leading to a severe decrease in lung diffusing capacity and compliance (Ashbaugh et al, 1967). Survivors are at high risk of developing cognitive decline, depression, post-traumatic stress, and the classic side effects of long-term care, such as polyneuropathy, sarcopenia, or stroke disorder, sleep. In this context and in spite of significant progress in the field of mechanical ventilation and extra-corporeal respiratory assistance, it remains essential to identify early patients with ARDS in order to offer them the most appropriate therapy as soon as possible
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