Increased systemic growth differentiation factor 15 is related to fixed airway obstruction and exacerbation rate in asthma

Background: Asthma is related to the increased risk of thromboembolic complications. Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine with anti-inflammatory and pro-fibrotic properties, known to be associated with cardiovascular risk. Methods: In 157 adult asthma patients and 60 matched controls, we determined plasma GDF-15 in relation to inflammatory and prothrombotic markers, including thrombin generation profile, fibrinolysis (clot lysis time, CLT), and cellular fibronectin. We also assessed the asthma exacerbation rate during the 3-year follow-up. Results: Asthma patients exhibited 10.8% higher GDF-15 levels (p < 0.001), which correlated positively with longer CLT, reflecting impaired fibrinolysis (r = 0.39, p < 0.001), cellular fibronectin (r = 0.37, p < 0.001), and C-reactive protein (r = 0.18, p = 0.025) but not with thrombin generation parameters. Baseline GDF-15 levels were not associated with asthma severity or FEV ₁ , but were higher (by 13.9%) in those with fixed airway obstruction (p = 0.024). In the follow-up, we documented 150 severe asthma exacerbations in 50 patients (33.3%), who had 12.3% higher GDF-15 at baseline (p = 0.003). Conclusion: This study is the first to demonstrate that circulating GDF-15 levels are higher in asthma and remain associated with fixed airway obstruction and asthma exacerbation rate, suggesting a potential role for GDF-15 in asthma pathogenesis.