In this section
@article{Meldrum:2025:10.1186/s12931-025-03440-1,
author = {Meldrum, OW and Tiew, PY and Xu, H and Low, DY and Ivan, FX and Narayana, JK and Jaggi, TK and Ching, J and Chotirmall, SH},
doi = {10.1186/s12931-025-03440-1},
journal = {Respir Res},
title = {Integrated multi-omics profiling for risk stratification in Asians with COPD.},
url = {http://dx.doi.org/10.1186/s12931-025-03440-1},
volume = {27},
year = {2025}
}
TY - JOUR
AB - BACKGROUND: Comorbidity-based risk stratification in Chronic Obstructive Pulmonary Disease (COPD) incompletely captures inherent biological heterogeneity, particularly in Asian populations that demonstrate high-risk clinical phenotypes including prior pulmonary tuberculosis. We investigated whether integrated sputum multi-omics could improve risk stratification in an Asian COPD cohort. METHODS: We conducted a prospective, multicenter assessment of N = 56 Asians with established COPD, classified as high- (N = 25; cardiovascular or ex-tuberculosis) or low-risk (N = 31; diabetic or low-comorbidity) based on established co-morbidity phenotyping. Sputum was subjected to mucus analysis (MUC5AC, MUC5B, mucus solids, rheology), metabo-lipidomics (LC-MS/MS) and microbiome assessment (shotgun metagenomics). Multivariate statistics was employed to integrate datasets. RESULTS: High-risk Asian COPD demonstrates abnormal mucus biochemistry characterized by elevated MUC5AC; extensive metabo-lipidomic alterations characterized by dysregulated tryptophan-kynurenine metabolism and lipid remodeling with enrichment of lysophosphatidylcholines and triacylglycerols. Microbial networks are disrupted in high-risk patients, typified by antagonistic interactions driven by K. pneumoniae, H. influenzae and Neisseria spp. Integrative assessment combining all datasets partitioned the cohort into two clusters: SNF 1 (N = 34) and SNF 2 (N = 22), the former representing an unfavorable group characterized by exacerbations, hospitalizations, mucus dysfunction, microbial pathogens and dysregulated metabo-lipidomic pathways. Remarkably, 42% (N = 13 of 31) of the originally classified low risk COPD exhibited the unfavorable SNF 1 endotype, distinguished by more severe exacerbations (hospitalizations), K. pneumoniae and elevated hypoxanthine, creatine, spermine and phosphatidylcholines. CONCLUSION: Integrative multi-omics
AU - Meldrum,OW
AU - Tiew,PY
AU - Xu,H
AU - Low,DY
AU - Ivan,FX
AU - Narayana,JK
AU - Jaggi,TK
AU - Ching,J
AU - Chotirmall,SH
DO - 10.1186/s12931-025-03440-1
PY - 2025///
TI - Integrated multi-omics profiling for risk stratification in Asians with COPD.
T2 - Respir Res
UR - http://dx.doi.org/10.1186/s12931-025-03440-1
UR - https://www.ncbi.nlm.nih.gov/pubmed/41316171
VL - 27
ER -
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