Inflammatory molecular endotypes in bronchiectasis

Introduction: Bronchiectasis is traditionally considered to be characterised by neutrophilic inflammation. Multiple clinical trials of antibiotic and anti-inflammatory drugs have failed to meet their endpoints. Aim: To define groups of patients with bronchiectasis who have different types of lung inflammation and therefore may require an individualised approach to therapy. Methods: Sputum, serum and clinical information were collected from 245 individuals with bronchiectasis when clinically stable. 21 potential biomarkers were measured in sputum supernatant and serum by MSD multiplex or ELISA. Results: PCA identified 3 vectors driving heterogeneity (Fig 1). At the extremes of these vectors were eosinophilic and epithelial dominant (IL-5, IL-13 and Gro-α in sputum), systemic (GMCF, IL-6, VEGF, IL-10, IL1β in serum) and airway neutrophilic inflammation (neutrophil extracellular traps, resistin, TNFα, CXCL-8, IL-10, MMP9 and elastase). Disease severity in patients in the neutrophilic group was worse with increased BSI score & sputum volume and decreased FEV1%pred. Frequently exacerbating patients were identified in all groups. The majority of clinical parameters and treatment with inhaled corticosteroids and macrolides showed little difference between groups, although inhaled antibiotics were frequently used in the neutrophilic group. Interpretation: Bronchiectasis is composed of multiple inflammatory endotypes which may represent different “treatable traits”.