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Lookup NU author(s): Professor Anthony De SoyzaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The authors 2026. Background: Neutrophilic airway inflammation is associated with disease severity and exacerbation frequency in bronchiectasis. Neutrophil protease inhibition significantly reduced exacerbation rates in phase II and III trials in bronchiectasis, highlighting this disease feature as an important therapeutic target. Additional neutrophil targeting therapeutics are needed to reduce the burden of the disease. Herein, we describe the protocol for the AIR-NET trial, the first randomised, open-label, multifactorial, multicentre, adaptive platform trial for people with bronchiectasis, run via the EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) network, to investigate the safety and efficacy of several repurposed anti-inflammatory treatments. Methods and analysis: Participants with bronchiectasis confirmed by computed tomography, daily sputum production and evidence of active airway neutrophilic inflammation (based on a positive lateral flow test for neutrophil elastase (NE) activity), across 10 sites in the UK, will be randomised to one of several repurposed drugs with published evidence of effects on neutrophilic inflammation and acceptable safety profile (oral dose: disulfiram 400 mg once daily; dipyridamole 200 mg twice daily; doxycycline 100 mg once daily; n=42 per arm) or usual care, according to arm-specific eligibility criteria, and treated for 28 days. New arms will be added to the trial through an adaptive design. The primary end-point is change from baseline in sputum NE activity (a validated biomarker and surrogate of exacerbation risk) at day 28. Key secondary end-points include time-to-first exacerbation, quality of life questionnaires, neutrophil function and safety. Summary AIR-NET will establish a multi-centre network with integrated clinical and translational capabilities for the investigation of therapies in bronchiectasis aiming to identify key anti-inflammatory mechanisms and effective re-purposed treatments.
Author(s): Long MB, New JM, Stobo J, Band M, Mclaren-Neil F, Hull R, Gilmour A, Lind H, McIntosh E, Galloway R, Eke Z, Harris B, Singanayagam A, Shah A, Huang J, Wilkinson T, Loebinger MR, Haworth CS, Chotirmall SH, de Soyza A, Chalmers JD
Publication type: Article
Publication status: Published
Journal: ERJ Open Research
Year: 2026
Volume: 12
Issue: 2
Online publication date: 09/03/2026
Acceptance date: 23/08/2025
Date deposited: 15/04/2026
ISSN (electronic): 2312-0541
Publisher: European Respiratory Society
URL: https://doi.org/10.1183/23120541.00719-2025
DOI: 10.1183/23120541.00719-2025
Data Access Statement: The datasets generated during and/or analysed during the current study will be available upon request from the Chief Investigator (Professor James Chalmers, j.chalmers@dundee.ac. uk). Approval of requests will be at the discretion of the Chief Investigator. Data will be available after the primary publication of the relevant experimental arm; there is no end date for requests. Data will be transferred using an appropriate secure method and will be limited to only data required to perform the proposed analysis. Data will be anonymised or pseudonymised as appropriate. Patient consent for data sharing will be obtained at trial entry. The full details and terms of the transfer will be set out in a data sharing agreement.
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