Plasma fibrinogen, fractional exhaled nitric oxide (FeNO), and the novel fibrinogen-to-FeNO ratio (FFR) as biomarkers in stable bronchiectasis.

Introduction: Bronchiectasis is a chronic airway disease characterized by predominantly neutrophilic and occasionally eosinophilic inflammation. We aimed to evaluate the alterations and clinical relevance of plasma fibrinogen as a key player in neutrophilic inflammation, fractional exhaled nitric oxide (FeNO) as an indicator of eosinophilic inflammation, and the fibrinogen-to-FeNO ratio (FFR) as a novel biomarker in bronchiectasis.

Methods: We conducted a two-center, observational, cross-sectional study involving a total of 45 stable, non-cystic fibrosis bronchiectasis patients. Fibrinogen, FeNO, and FFR were measured and investigated in relation to respiratory symptoms, pulmonary function, radiological extension, airway infection, systemic inflammation, and validated disease severity scores.

Results: The 45 patients (33.3% males), with a median (interquartile range, IQR) age of 71 (22.4) years, presented a median (IQR) fibrinogen of 389 (152.7) mg/dL, FeNO of 18 (15.5) ppb, and FFR of 1.2 (1.3). Fibrinogen (1) and FeNO (2) were positively or negatively statistically significantly correlated with the percentage of predicted forced expiratory volume in 1 second (FEV₁%Pred, r₁=-0.476/p₁=0.002 and r₂=+0.470/p₂=0.038, respectively), total white blood cells (WBC, r₁=+0.373/p₁=0.012 and r₂=-0.411/p₂=0.013, respectively), and serum C-reactive protein (CRP, r₁=+0.750/p₁<0.001 and r₂=-0.330/p₂=0.057, respectively). Fibrinogen was additionally correlated with the number of affected lung lobes (r=+0.308/p=0.042) and erythrocyte sedimentation rate (r=+0.493/p=0.001). Interestingly, FFR was found to more strongly correlate with the FEV₁%Pred (r=-0.606/p<0.001), total WBC (r=+0.471/p=0.006), serum CRP (r=+0.592/p<0.001), blood neutrophils (r=+0.357/p=0.042) and eosinophils (r=-0.390/p=0.025), and the severity of airway infection based on the isolated pathogens, including Pseudomonas aeruginosa as the cardinal pathogen (r=+0.444/p=0.034).

Conclusions: In the context of the verified clinical importance of fibrinogen and FeNO, FFR is introduced as a novel potential biomarker in bronchiectasis, reflecting the balance between neutrophilic and eosinophilic inflammation and associating with key aspects of disease activity and severity.

*AMM and NB contributed equally.