Neutrophilic-dominant phenotype during exacerbations predicts adverse hospital outcomes in asthma-bronchiectasis overlap syndrome

Background Exacerbations of asthma-bronchiectasis overlap syndrome (ABOS) are clinically heterogeneous, with poorly defined inflammatory phenotypes and their links to outcomes.Objective To identify phenotypes in ABOS exacerbations and their associations with in-hospital outcomes.Methods In this prospective study, 343 patients with ABOS exacerbation were clustered using multidimensional data; findings were validated in 147 independent patients. Associations between phenotypes and outcomes (Intensive Care Unit [ICU] admission, invasive mechanical ventilation [IMV], mortality) were analyzed via multivariable regression.Results Three phenotypes were identified: female-paucigranulocytic (Cluster T1), young male-eosinophilic (Cluster T2), and neutrophilic-lymphopenic (Cluster T3). Cluster T3 had the highest risks of ICU admission (adjusted relative risk [RRadj] = 7.84, 95% CI: 2.21–27.78), IMV (RRadj=7.84, 95% CI: 2.21–27.78), and mortality (RRadj=6.86, 95% CI: 2.33–37.67). Neutrophilia showed a dose-dependent association with adverse outcomes (Ptrend<0.001), with elevated levels independently predicting composite outcomes (RRadj=2.06, 95% CI: 1.42–3.03).Conclusions ABOS exacerbations exhibit distinct inflammatory phenotypes. The neutrophilic-lymphopenic phenotype strongly predicts in-hospital adverse outcomes, highlighting its potential for acute risk stratification in hospitalized patients.