Refining prognostic risk stratification in bronchiectasis: the heterogeneous role of Pseudomonas aeruginosa by inflammatory phenotype

Whether chronic Pseudomonas aeruginosa (PA) colonisation differentially affects the risk of exacerbations and their subsequent hospitalisation across inflammatory phenotypes in bronchiectasis remains unknown. We examined phenotype‑specific associations to identify high-risk subgroups for targeted PA management. This single-centre retrospective cohort included 625 stable bronchiectasis patients classified into paucigranulocytic ( n = 331), neutrophilic ( n = 204), eosinophilic ( n = 47), and mixed-granulocytic ( n = 43) phenotypes based on combined blood eosinophil (≥ 300 cells/µL) and neutrophil (≥ 4990 cells/µL) counts. Exacerbations (with hospital-requiring events as a severe subset) were the primary outcome. Adjusted Cox and modified Poisson models assessed PA colonisation’s impact on time-to-first and 1-year binary exacerbations, respectively. Overlap-weighted sensitivity analyses and bronchoalveolar lavage fluid (BALF) immune profiling (in available subsets) were performed. Overall, 10.7% (67/625) of patients were PA-colonised, with the highest prevalence in the mixed-granulocytic phenotype (20.9%, 9/43). No statistically significant overall association was found for either outcome. Phenotype-stratified analyses showed PA colonisation significantly shortened time to first exacerbation (aHR 2.18, 95% CI 1.20–3.97, P = 0.011) and increased 1-year exacerbation risk (aRR 1.82, 95% CI 1.22–2.72, P = 0.003) in the neutrophilic phenotype, whereas it significantly shortened time to first hospitalisation (aHR 10.46, 95% CI 1.77–61.72, P = 0.010) and increased 1-year hospitalisation risk (aRR 5.33, 95% CI 1.78–15.99, P = 0.003) in the mixed-granulocytic phenotype. Adjusted PA-phenotype interaction P values were 0.030 for first exacerbation and 0.047 for first hospital-requiring exacerbation. Overlap‑weighted analyses corroborated these findings. Exploratory BALF profiling suggested associations between PA colonisation and higher IL-2, IL-4, and CD8 + CD28 + T-cell levels in the neutrophilic and mixed-granulocytic phenotypes, with elevations of IL‑12 and IFN‑α confined to the neutrophilic phenotype and CD4 + CD29 + T‑cell elevation to the mixed-granulocytic phenotype. PA colonisation was associated with distinct exacerbation outcomes across inflammatory phenotypes. Neutrophilic phenotype patients are susceptible to overall exacerbations, whereas mixed-granulocytic patients are vulnerable to severe events requiring hospitalisation, highlighting the potential relevance of inflammatory phenotypes to PA-related risk stratification. Clinical trial number: not applicable.