“High-Risk” Asian COPD characterized by mucus-metabolic-microbial dysbiosis

<bold>INTRODUCTION:</bold> Prior research identified “high-risk” Asian COPD patient clusters with high mortality and inflammation. However, analysis of mucus, metabolic and microbial profiles in these groups remain unexplored. <bold>METHODS:</bold> Prospective assessment of 56 COPD patients including mucus (biochemical and biophysical), metabolic (targeted metabolomics and lipidomics) and microbial (metagenomics) profiles. Multivariable associations (MaAsLin2) analyzed dysbiosis in relation to COPD risk groups and clinical outcomes. <bold>RESULTS:</bold> “High-risk” groups (i.e. Cardiovascular: CVS and Ex-TB) showed significantly higher exacerbation frequency (p< 0.01) and GOLD classification (A, B, E; p<0.05) versus “low-risk” groups (i.e. diabetes and low comorbidity). Notable were increased mucus % solids, MUC5AC concentration and MUC5AC/MUC5B ratio (all p<0.05 and p<0.01 for CVS and ex-TB, respectively). Metabolic dysbiosis in “high-risk” groups involved inflammatory pathways, notably tryptophan and linoleic acid metabolism. Combined analysis revealed strong links between mucus biochemistry, metabolic dysregulation and microbial dysbiosis. <bold>CONCLUSION:</bold> Mucus-metabolic-microbiome profiles in “high-risk” Asian COPD patients revealed key inter-relationships involving mucus hyper-concentration, metabolic dysregulation and microbial dysbiosis, offering fresh insight into ex-TB pathogenesis. <bold>FUNDING:</bold> Supported by LKCMedicine–ICL Fellowship (#020458-00001) (O.W.M), Singapore Ministry of Health’s National Medical Research Council under the Clinician-Scientist Individual Research Grant MOH-001356 (S.H.C.), Clinician-Scientist Award MOH-000710 (S.H.C) and the Singapore Ministry of Education (AcRF Tier 1 Grant RT1/22) (S.H.C).