Eosinophilic inflammation amplifies the prednisolone-induced prothrombotic state in asthma

Background: Patients with asthma are at increased risk to develop pulmonary embolism. Recently we showed that corticosteroids have a prothrombotic effect in patients with asthma. It is unknown whether this effect is modified by the intensity of eosinophilic inflammation. Aim: To compare the prothrombotic effect of prednisolone between patients with high and low blood eosinophils or exhaled nitric oxide (FeNO). Methods: 60 patients with stable asthma received either prednisolone 0.5mg/kg/day (n=30) or placebo (n=30) for 10 days. Treatment arms were stratified according to number of blood eosinophils (median 0.23 x 10 9 /L) or FeNO (median 25 ppb) at baseline. Changes from baseline in plasma markers of coagulation (peak thrombin and area under the curve of in vitro thrombin generation (ETP), thrombin-antithrombin complexes (TATc)), fibrinolysis (D-dimer, plasminogen activator inhibitor type-1 (PAI-1), plasmin-α2-antiplasmin complexes (PAPc)), and endothelial activation (von Willebrand factor (vWF)) were compared between prednisolone and placebo in the high and low eosinophil or FeNO groups. Results: Prednisolone increased vWF in both high and low eosinophil groups. However, compared to placebo prednisolone increased PAI-1 9.0 ng/mL (IQR 2.0 – 12.0) and peak thrombin (14.2% (8.6 – 28.2) in the high, but not in the low eosinophil group (p Conclusion: Eosinophilic inflammation amplifies the prednisolone-induced prothrombotic state in asthma. This suggests that patients with eosinophilic asthma are at highest risk of pulmonary embolism.