¹H-NMR-based metabolic profiling of healthy individuals and high-resolution CT-classified phenotypes of COPD with treatment of tiotropium bromide

Li-Chuan Tan,¹ Wen-Jie Yang,² Wei-Ping Fu,¹ Ping Su,² Jing-Kui Shu,¹ Lu-Ming Dai<sup>1

1</sup>Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; ²Department of Respiratory, Baoshan People’s Hospital, Baoshan 678000, People’s Republic of China

Background: Heterogeneity of COPD results in different therapeutic effects for different patients receiving the same treatment. COPD patients need to be individually treated according to their own characteristics. The purpose of this study was to explore the differences in different CT phenotypic COPD by molecular metabolites through the use of metabolomics.
Methods: According to the characteristics of CT imaging, 42 COPD patients were grouped into phenotype E (n=20) or phenotype M (n=24). Each COPD patient received tiotropium bromide powder for inhalation for a therapeutic period of 3 months. All subjects were assigned into phenotype E in pre-therapy (EB, n=20), phenotype E in post-therapy (EA, n=20), phenotype M in pre-therapy (MB, n=22), phenotype M in post-therapy (MA, n=22), or normal control (N, n=24). The method of metabolomics based on ¹H nuclear magnetic resonance (¹H-NMR) was used to compare the changes in serum metabolites between COPD patients and normal controls and between different phenotypes of COPD patients in pre- and post-therapy.
Results: Patients with COPD phenotype E responded better to tiotropium bromide than patients with COPD phenotype M in terms of pulmonary function and COPD assessment test scores. There were differences in metabolites in COPD patients vs normal control people. Differences were also observed between different COPD phenotypic patients receiving the treatment in comparison with those who did not receive treatment. The changes of metabolites involved lactate, phenylalanine, fructose, glycine, asparagine, citric acid, pyruvic acid, proline, acetone, ornithine, lipid, pyridoxine, maltose, betaine, lipoprotein, and so on. These identified metabolites covered the metabolic pathways of amino acids, carbohydrates, lipids, genetic materials, and vitamin.
Conclusion: The efficacy of tiotropium bromide on COPD phenotype E is better than that of phenotype M. Metabolites detected by ¹H-NMR metabolomics have potentialities of differentiation of COPD and healthy people, discrimination of different COPD phenotypes, and giving insight into the individualized treatment of COPD.

Keywords: COPD, metabolomics, tiotropium bromide, CT phenotyping, individualized treatment