Characterising patients with bronchiectasis and persistently negative sputum cultures: data from the European Bronchiectasis Registry EMBARC.

<bold>Introduction:</bold> 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. <bold>Methods:</bold> 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. <bold>Results:</bold> 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). <bold>Conclusion:</bold> 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.