Plasma Fibrinogen-to-Fractional Exhaled Nitric Oxide Ratio (FFR) as an Emerging Biomarker in Bronchiectasis

Background and Aims: Plasma fibrinogen and fractional exhaled nitric oxide (FeNO) reflect neutrophilic and eosinophilic airway inflammation, respectively, and are associated with disease activity and severity in different directions in bronchiectasis. This study aimed to concurrently investigate fibrinogen and FeNO and further evaluate the clinical importance of fibrinogen-to-FeNO ratio (FFR) as a composite biomarker in bronchiectasis. Methods: This was a two-centre, observational, cross-sectional study involving stable bronchiectasis patients. Fibrinogen, FeNO, and the ratio of their normalised values (FFR) were investigated in relation to clinical indicators of disease activity and severity, including respiratory symptoms, inflammatory markers, pulmonary function, radiological extent, airway infection, severity scores, and patient-reported outcomes. Results: FFR was correlated with both circulating neutrophils (r = 0.36, p = 0.04) and eosinophils (r = -0.39, p = 0.03) and, more strongly compared to fibrinogen and FeNO, with the percentage of predicted forced expiratory volume in the 1st second (r = -0.61, p < 0.001). Interestingly, only FFR was found to be higher in patients with Pseudomonas aeruginosa isolation in respiratory secretions (p < 0.01). In receiver operating characteristic curves, FFR showed good discriminatory ability to differentiate patients with any level (AUC: 0.80, 95% CI: 0.64-0.96) or a severe level (AUC: 0.83, 95% CI: 0.64-1.00) of pulmonary functional impairment and patients with severe disease (AUC: 0.78, 95% CI: 0.62-0.94). Conclusions: FFR emerges as a candidate biomarker capturing the balance between neutrophilic and eosinophilic inflammation and the net disease activity and severity in bronchiectasis.