TY - JOUR T1 - Sputum protein profiling identifies a key role for neutrophil extracellular traps in exacerbations of bronchiectasis and treatment response JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.lungscienceconference-2019.PP112 VL - 5 IS - suppl 2 SP - PP112 AU - Holly Rachael Keir AU - Brandon Tan AU - Christopher John Fong AU - Alison Dicker AU - Guillermo Suarez-Cuartin AU - Oriol Sibila AU - Megan Louise Crichton AU - Andrew Cassidy AU - Simon Finch AU - Eleanor Pumphrey AU - Thomas Fardon AU - Jeffrey Huang AU - James D Chalmers Y1 - 2019/03/07 UR - http://openres.ersjournals.com/content/5/suppl_2/PP112.abstract N2 - Introduction: Bronchiectasis (BE) is a heterogeneous disease and antibiotics are a main treatment. Recent trials suggest clinical response to antibiotics is unpredictable. We used proteomic approaches to study patients with BE when clinically stable and following antibiotic treatment.Methods: Sputum samples were collected from 20 BE patients on day one of an exacerbation, and 14 days post-antibiotic treatment. Label Free LC/MS was used to profile sputum samples. Biomarkers, including neutrophil extracellular traps (NETs) were measured using immunoassays. Results were validated in 333 stable patients with BE.Results: 20 patients were included in the proteomic study. 55% of patients had Pseudomonas aeruginosa (PA) infection. In the proteomic analysis, there was a differential response to antibiotics in patients with baseline PA. The expression of NET proteins showed a greater decrease after antibiotic treatment in the non-PA group. Three endotypes of BE treatment response were identified with distinct proteomic patterns: type 1 events associated with NET clearance and improvements in symptoms/FEV1, type 2 events with minimal proteomic changes and minimal clinical response, type 3 events where response was mixed. Candidate biomarkers were validated which showed heterogeneous responses post antibiotics. In a validation study in 333 stable patients, sputum NET complexes correlated with FEV1% predicted(p<0.0001), risk of severe exacerbation(p<0.0001) and the BE severity index(p<0.0001).Conclusion: We identified novel endotypes of BE exacerbations and treatment responses which may be used in future for personalised therapy.FootnotesCite this article as: ERJ Open Research 2019; 5 : Suppl. 2, PP112.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this conference is available at www.ers-education.org (ERS member access only). ER -