Clinical and Inflammatory Phenotypes During Exacerbations Predict In‐Hospital Adverse Outcomes in Asthma‐
COPD
Overlap
Lishan Yuan, Lei Wang, Yulai Yuan, Yilai Li, Li Zhang, Ying Liu, Lei Liu, Lingyun Lu, Min Feng, Gang Wang, Shuwen Zhang, Chongyang Zhao, Qin Wang, Deying Kang, Xin Zhang ABSTRACT
Background and Objectives
Exacerbations of asthma–chronic obstructive pulmonary disease overlap (EACO) are associated with high mortality, yet the acute‐phase heterogeneity remains poorly characterized. This study aimed to identify distinct inflammatory phenotypes of EACO during hospitalization and evaluate their associations with clinical outcomes.
Methods
A prospective two‐centre cohort study enrolled 2444 EACO patients (training and validation cohort). Baseline inflammatory markers and clinical data were collected. Unsupervised k‐means clustering identified inflammatory phenotypes, with sensitivity analysis excluding demographic variables. In‐hospital clinical outcomes (ICU admission, invasive ventilation, in‐hospital mortality) were assessed. Logistic regression and causal mediation analysis evaluated phenotype–outcome associations. A nomogram was developed and validated using receiver operating characteristic curves (AUC).
Results
Three distinct phenotypes were identified: Cluster T1 (neutrophil‐to‐lymphocyte ratio [NLR]‐elevated hypoeosinophilic systemic inflammatory), Cluster T2 (eosinophilic), and Cluster T3 (eosinophil‐neutrophil balanced). Cluster T1 exhibited systemic hyperinflammation (elevated white blood cell count, neutrophils, NLR, C‐reactive protein (CRP), procalcitonin (PCT), and interleukin‐6 (IL‐6)), and the highest composite adverse outcome rate (24.2%; p < 0.001). Logistic regression revealed absolute neutrophil count (β = 0.38, p < 0.001), D‐dimer (β = 0.25, p < 0.001), and absolute lymphocyte count (β = −0.41, p < 0.001) as key outcome predictors, confirmed by causal mediation analysis. The nomogram showed robust predictive performance (AUC training = 0.775; validation = 0.766).
Conclusion
Inflammatory phenotypes during EACO predict differential in‐hospital outcomes, with neutrophil‐dominant phenotypes conferring the highest risk. Early phenotype‐based risk stratification using simple blood biomarkers may guide individualized EACO management.