Temporal Changes in Microrna Expression in Blood Leukocytes from Patients with the Acute Respiratory Distress Syndrome

Abstract

Background MicroRNA (miRNA) control gene transcription by binding to and repressing the translation of messenger RNA (mRNA). Their role in the acute respiratory distress syndrome (ARDS) is undefined. Methods Blood leukocytes from 51 patients enrolled in a prior randomized trial of corticosteroids for ARDS were analyzed. After screening eight patients with microarrays for altered miRNA expression, 25 miRNAs were selected for further analysis using RT-PCR in all 51 patients. Results On day 0, the 51 patients had APACHE III score of 60.4 ± 17.7 and PaO2/FiO2 of 117 ± 49. 21 miRNA were expressed at increased levels in blood leukocytes at the onset of ARDS compared to healthy controls. These miRNA remained elevated at day 3 and increased further by day 7 (log2 fold change from 0.66 to 5.7 fold, p <0.05 compared to day 0). In a subgroup analysis (37 patients treated with corticosteroids and 14 treated with placebo), the interaction of miRNA expression over time and steroid administration was not significant suggesting that systemic corticosteroids had no effect on the miRNA detected in our study. In contrast, corticosteroids but not placebo decreased IL-6 and C-reactive protein at day 3 (p<0.001) demonstrating an early systemic anti-inflammatory response whereas both treatment arms had decreased values by day 7 (p<0.001). Conclusions Expression of miRNA are increased in blood leukocytes of patients with ARDS at day 0 and day 3 and rise further by day 7, when systemic inflammation is subsiding. These effects appear independent of the administration of steroids, suggesting different inflammatory modifying roles for each in the resolving phases of ARDS.

Increased mortality in elderly patients with acute respiratory distress syndrome is not explained by host response

“…Potential age-dependent differences in the host response at a later time point could exist and may also explain outcome differences. Studies have suggested that a prolonged inflammatory response is associated with an adverse outcome [50, 51]. Moreover, there is evidence of age-dependent temporal differences in the host response in critically ill patients (e.g., a hyper-inflammatory response during the later phase of disease and a prolonged inflammation in elderly) [17, 20, 52–56].…”

Effect of Different Dosages of Dexamethasone Therapy on Lung Function and Inflammation in an Early Phase of Acute Respiratory Distress Syndrome Model

“…Dexamethasone positively influenced the lung functions and attenuated inflammation (Mokra et al 2007, Kosutova et al 2016. There is also increasing evidence that lower dose of GC administered earlier after developing ARDS could be beneficial (Meduri et al 2007, Narute et al 2017, Yang et al 2017. However, due to heterogeneous nature of ARDS the appropriate dosing regimens, timing and duration of GC therapy as well as reasonability for their use are still discussed.…”

Current Concepts of ARDS: A Narrative Review

“…miRNA have shown to regulate genes involved in normal lung physiology and inflammatory lung states [ 114 ]. A recent paper studied miRNA present in blood leukocytes of patients with ARDS during the first week of care, with a particular focus on the effects of corticosteroid therapy on miRNA expression during the first week of care [ 115 ]. The authors identified 21 miRNA that are expressed at increased levels at the onset of ARDS, remain elevated at day 3 and increase further by day 7, suggesting that the underlying inflammatory processes that led to ARDS remained active at day 3 and the enhanced miRNA expression by day 7 may have a role in the resolution of inflammation.…”