M18 Heparin-binding protein as a biomarker inflammation, symptoms and severity in bronchiectasis

<h3>Introduction</h3> HPB is stored in azurophilic granules and secretory vesicles of neutrophils. It is released rapidly in the context of neutrophilic inflammation. HBP acts as an opsonin to enhance phagocytosis of pathogens but is also pro-inflammatory and promotes endothelial and epithelial dysfunction. We sought to investigate the role of HBP in bronchiectasis. <h3>Methods</h3> 121 adult patients with CT confirmed bronchiectasis were included. HBP concentration in sputum supernatant was measured using a validated ELISA assay. Severity of disease was evaluated using the bronchiectasis severity index (BSI) and FACED, forced expiratory volume in 1 second (FEV1) and correlated with established markers of bronchiectasis severity including neutrophil elastase (NE). Patients were followed-up for 3 years for longitudinal outcomes. <h3>Results</h3> HBP concentrations showed a moderate positive correlation to other neutrophilic markers in sputum such as NE (r=0.52, p&lt;0.0001). HBP concentrations showed a positive correlation to MRC dyspnoea score (r=0.32, p=0.004) and a negative correlation to FEV1 (r=-0.24, p=0.0086). Higher sputum HBP was associated with more severe radiological disease (r=0.39, p&lt;0.001) and severity indices BSI (r=0.445, p&lt;0.0001) and FACED (r=0.34, p=0.001). During long term follow-up a level of HBP above the population median was associated with a shorter time to first hospitalization and exacerbation (Hazard Ratio (HR) 3.37, 95%CI 1.81–6.27, p&lt;0.0001) and exacerbations (HR 1.49 95% CI 0.98–2.26, p=0.06). <h3>Conclusions</h3> HBP is a potential biomarker of airway inflammation and disease severity in patients with bronchiectasis. Future studies should establish whether HBP has prognostic or therapeutic implications and determine its role in the pathogenesis of bronchiectasis.