Abstract Background The heterogeneity of bronchiectasis is well-recognized, with disease burden and outcomes varying across clinical phenotypes and inflammatory endotypes. However, the relationship between blood cell count-based inflammatory endotypes and the airway microbiome, clinical features, and exacerbation risk remains unclear. Methods This single-center prospective study categorized bronchiectasis patients into four inflammatory subtypes based on blood counts: neutrophilic (Neu, n = 66), eosinophilic (Eos, n = 44), mixed granulocytic (Mixed, n = 56), and paucigranulocytic (Pauci, n = 59), using cutoff values of 4.4 × 109/L for neutrophils and 0.15 × 109/L for eosinophils. Sputum samples underwent 16S rRNA sequencing, and clinical data were collected. Results The Mixed group showed the most severe lung function impairment, radiographic extent, and Bronchiectasis Severity Index (BSI) scores, followed by Neu, Eos, and Pauci groups (P 0.05). Bronchodilator use was highest in the Mixed group. Microbiome composition was similar across groups, predominantly featuring Proteobacteria (mainly Pseudomonas), with no significant separation. Although the Neu group had the lowest Shannon diversity, the difference was not statistically significant. Neisseria abundance was significantly lower in the Neu versus Eos group (P 0.05). Linear discriminant analysis identified Neisseria, Ruminococcaceae, Carnobacteriaceae, and Alteromonadaceae as key discriminators among endotypes. Core genera, particularly Pseudomonas, correlated significantly with disease duration, 24-hour sputum volume, BSI, lung function, and radiographic severity (P 0.05). In the follow-up cohort (n = 125), no significant differences in exacerbation risk were observed among endotypes. Additionally, these inflammatory subtypes demonstrated high robustness over time during stable disease. Conclusion This study demonstrates that blood cell-based inflammatory endo-typing in bronchiectasis identifies distinctions in disease burden and airway microbiome, with the endotypes exhibiting high robustness. However, this endotype approach has limited efficacy in identifying patients at high risk for future acute exacerbations. Future research should systematically compare the predictive performance of blood cell-based and sputum cell-based endotypes for acute exacerbation risk. This abstract is funded by: Noncommunicable Chronic Diseases - National Science and Technology Major Project (No. 2024ZD0529600, W.J.G; No.2024ZD0541300, Z.F.H.)
He et al. (Fri,) studied this question.