Increased blood levels of cellular fibronectin in asthma: Relation to the asthma severity, inflammation, and prothrombotic blood alterations

Science and Research

BACKGROUND: Recently, we have reported that asthma is characterized by prothrombotic blood alterations, which were related to the low-grade inflammatory state. Inflammation, however, may also lead to vascular dysfunction. The aim of this study was to evaluate plasma levels of cellular fibronectin (cFN), a marker of vascular injury in asthmatics, and to analyze their impact on described previously prothrombotic blood alterations. METHODS: In a cross-sectional study, we investigated 164 adult stable asthmatics and 72 matched controls. Plasma cFN was measured using an ELISA. Its relations to inflammation, thrombin generation, fibrinolytic capacity, expressed as clot lysis time (CLT), and platelet markers were evaluated. RESULTS: Asthma was associated with 50.1% higher plasma cFN levels as compared with controls (p<0.001, after adjustment for potential confounders). There was a positive association of cFN with asthma severity and inverse with the FEV1/VC index (beta=0.2 [95%CI:0.13-0.28] and beta=-0.15 [95%CI: -0.23 to -0.07], respectively). In asthmatics cFN positively correlated with high-sensitivity C-reactive protein (beta=0.24 [95%CI:0.16-0.32]), fibrinogen (beta=0.13 [95%CI:0.04-0.21]), interleukin-6 (beta=0.23 [95%CI:0.15-0.3]), platelet factor 4 (beta=0.14 [95%CI:0.06-0.21]), plasminogen (beta=0.11 [95%CI:0.04-0.19]) and CLT (beta=0.35 [95%CI:0.28-0.42]). In both groups cFN was related to the endogenous thrombin potential (ETP) (beta=0.51 [95%CI:0.44-0.57], and beta=0.17 [95%CI:0.07-0.27], respectively). Multiple regression models showed that cFN was the most potent independent predictor of both ETP and CLT in asthmatics. CONCLUSION: Presented study is the first to show increased plasma cellular fibronectin in asthma, which is associated with disease severity, inflammation, and prothrombotic blood alterations. This novel observation suggests a previously unknown modulator of prothrombotic plasma properties in asthmatics.