Single-Cell RNA Sequencing Validated Key Hematological Biomarkers for Diagnosing Asthma-COPD Overlap
Description
Asthma–COPD overlap (ACO) is a heterogeneous respiratory syndrome that combines the pathological features of asthma and chronic obstructive pulmonary disease (COPD), posing substantial obstacles to accurate clinical diagnosis and personalised management. Reliable haematological biomarkers are urgently needed to improve the classification and prognostic assessment of ACO. In this ten-year retrospective cohort study, 53 951 participants were enrolled and stratified into healthy control, pure asthma, pure COPD and ACO cohorts. Significant intergroup disparities in age distribution, sex ratio and routine peripheral-blood inflammatory indices were identified across the four cohorts. Correlation analyses confirmed stable associations among core inflammatory indicators, including the neutrophil-tolymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR). External validation using public single-cell RNA sequencing (scRNA-seq) datasets revealed consistent shifts in the pulmonary proportions of neutrophils, lymphocytes and eosinophils across the four groups at the tissue level; these tissue-level changes closely recapitulated the peripheralblood immune phenotypes, corroborating the biological reliability of the circulating markers. When the screened core haematological indicators were incorporated into Bayesian machine-learning models, eosinophils (EOS), neutrophils (NEUT) and lymphocytes (LYMP) showed the strongest predictive value, and the final combined Bayesian classifier achieved robust discrimination for ACO, asthma and COPD risk stratification. Collectively, our findings demonstrate the biological consistency and clinical practicability of these key peripheral immune biomarkers for the auxiliary diagnosis of ACO. The resulting non-invasive predictive model supports precise clinical evaluation and individualised intervention for chronic obstructive airway disorders.