Prevention or Treatment of Ards With Aspirin

Abstract

Background The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. Methods We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. Results The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. Conclusion This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose, before prospective randomized trials.

What’s in a Number? Platelet Count Dynamics as a Novel Mediator of Acute Respiratory Distress Syndrome Survival

“…There has been strong interest in therapeutically targeting platelet activity in ARDS. Although the LIPS-A (Lung Injury Prevention Study with Aspirin) study did not find a reduced risk of ARDS for high-risk subjects randomized to aspirin therapy over placebo, there are ongoing efforts to target platelets for ARDS therapy (11)(12)(13). The gene expression data in the present manuscript strengthens the candidacy of rs9358856 as a functional variant and may contribute to our understanding of platelet homeostasis.…”

Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse

“…In line with these data a recent prospective study using a human model of ARDS suggests that reduced platelet activation via aspirin administration significantly reduces acute pulmonary neutrophilia ( 17 ). However, meta-analysis of clinical studies using aspirin in the management of ARDS concluded that data are insufficient to justify the use of aspirin as yet ( 44 ). Interestingly, an injurious role for platelet CLEC-2 during a mouse model of deep vein thrombosis was recently reported ( 46 ), with platelet transfusion shown to be protective in mice that were first subjected to extracorporeal circulation ( 34 ) or during mouse models of sepsis ( 57 ).…”

Timing of valproic acid in acute lung injury: prevention is the best therapy?

“…33–35 Despite the initial enthusiasm and encouraging results with aspirin as potential prevention or treatment for ARDS, 36 a prospective randomized trial of aspirin in at-risk patients presenting to the emergency department (The LIPS-A Randomized Clinical Trial) failed to reduce risk of ARDS compared to placebo, and the participating authors concluded that the results of their phase 2b trial did not support continuation to a larger phase 3 trial. 37 …”