Introduction
Chronic infection with pathogens is a key feature of bronchiectasis. Despite this, some patients will have persistently negative sputum cultures despite high disease burden.  This group of patients has not been previously described or characterised. 
Methods
We examined patients enrolled into the European Bronchiectasis registry (EMBARC) between 2015 and 2022. We defined negative microbiology as at least 2 negative samples with no positive samples in the year prior to baseline in the registry.
Results
18843 patients were included in the study.  28272 sputum samples were sent during the study period, 17237 (61%) at stable state and 11035 (39%) at exacerbation. 6082 patients had at least 2 cultures available. 1152 (18.9%) of patients with at least 2 samples sent were found to have persistently negative cultures and compared with 4923 with at least one positive culture.  Persistently negative cultures were associated with current smoking (7.5% vs 4.5%), a lower daily sputum volume (mean 37.5mls vs 48mls) and less severe disease. This group of patients was not strongly associated with a particular aetiology of bronchiectasis except for inflammatory Bowel Disease (IBD) (OR 2.0). Patients with persistently negative cultures had a similar rate of exacerbations (rate ratio 0.92 95%CI 0.83-1.02p=0.092) but lower hospitalisation rate (RR 0.84 95%CI 0.72-0.98, p=0.02) and lower mortality HR0.76 95%CI 0.59-0.98, p=0.03).
Conclusion
18.9% patients with 2 or more sputum samples sent have persistently negative cultures.  This group are not easily distinguishable from the group with airway infection and includes patients with high disease burden.