Induced sputum metabolomic profiles and oxidative stress are associated with chronic obstructive pulmonary disease (COPD) severity: potential use for predictive, preventive, and personalized medicine

Tao Zhu; Shanqun Li; Jiajia Wang; Chunfang Liu; Lei Gao; Yuzhen Zeng; Ruolin Mao; Bo Cui; Hong Ji; Zhihong Chen

doi:10.1007/s13167-020-00227-w

Induced sputum metabolomic profiles and oxidative stress are associated with chronic obstructive pulmonary disease (COPD) severity: potential use for predictive, preventive, and personalized medicine

EPMA J. 2020 Nov 4;11(4):645-659. doi: 10.1007/s13167-020-00227-w. eCollection 2020 Dec.

Authors

Tao Zhu^#¹, Shanqun Li^#², Jiajia Wang³, Chunfang Liu², Lei Gao², Yuzhen Zeng², Ruolin Mao², Bo Cui², Hong Ji⁴, Zhihong Chen²

Affiliations

¹ Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 China.
² Department of Respiratory and Critical Care Medicine, Zhongshan Hospital of Fudan University, Shanghai, 20032 China.
³ Rheumatology Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 China.
⁴ California National Primate Research Center, and Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616 USA.

^# Contributed equally.

Abstract

Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous disease, and metabolomics plays a hub role in predictive, preventive, and personalized medicine (PPPM) related to COPD. This study thus aimed to reveal the role of induced sputum metabolomics in predicting COPD severity. In this pilot study, a total of 20 COPD patients were included. The induced sputum metabolites were assayed using a liquid chromatography-mass spectrometry (LC-MS/MS) system. Five oxidative stress products (myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH), neutrophil elastase (NE), and 8-iso-PGF2α) in induced sputum were measured by ELISA, and the metabolomic profiles were distinguished by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis, and a significant difference in induced sputum metabolomics was observed between moderate and severe COPD. The KEGG analysis revealed that the glycerophospholipid metabolism pathway was downregulated in severe COPD. Due to the critical role of glycerophospholipid metabolism in oxidative stress, significant negative correlations were discovered between glycerophospholipid metabolites and three oxidative stress products (SOD, MPO, and 8-iso-PGF2α). The diagnostic values of SOD, MPO, and 8-iso-PGF2α in induced sputum were found to exhibit high sensitivities and specificities in the prediction of COPD severity. Collectively, this study provides the first identification of the association between induced sputum metabolomic profiles and COPD severity, indicating the potential value of metabolomics in PPPM for COPD management. The study also reveals the correlation between glycerophospholipid metabolites and oxidative stress products and their value for predicting COPD severity.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-020-00227-w.

Keywords: Chronic obstructive pulmonary disease (COPD); Glycerophospholipid metabolism pathway; Induced sputum; Lung function; Metabolomics; Predictive preventive personalized medicine (PPPM).

Abstract

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