Metabolic Fingerprinting Uncovers the Distinction Between the Phenotypes of Tuberculosis Associated COPD and Smoking-Induced COPD

Da Jung Kim; Jee Youn Oh; Chin Kook Rhee; Seoung Ju Park; Jae Jeong Shim; Joo-Youn Cho

doi:10.3389/fmed.2021.619077

Metabolic Fingerprinting Uncovers the Distinction Between the Phenotypes of Tuberculosis Associated COPD and Smoking-Induced COPD

Front Med (Lausanne). 2021 May 14:8:619077. doi: 10.3389/fmed.2021.619077. eCollection 2021.

Authors

Da Jung Kim^{1

2}, Jee Youn Oh³, Chin Kook Rhee⁴, Seoung Ju Park⁵, Jae Jeong Shim³, Joo-Youn Cho^{1

6}

Affiliations

¹ Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
² Seoul National University Medical Research Center, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
³ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea.
⁴ Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, South Korea.
⁵ Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, South Korea.
⁶ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

Background: Although smoking is considered the main cause of chronic obstructive pulmonary disease (COPD), several other risk factors, including pulmonary tuberculosis (TB), contribute significantly to disease causation, particularly in developing countries. However, the underlying pathogenesis of TB-associated COPD (T-COPD) is unclear. Moreover, the need for prompt diagnosis and treatment of T-COPD to decrease the future burden of inflammation is underestimated. This study aimed to identify distinctive endogenous metabotypes of T-COPD, compared to smoking-associated COPD (S-COPD). Methods: Cross-sectional metabolomic analyses and clinical examinations of serum samples were performed for three groups of 168 male subjects: T-COPD (n = 59), S-COPD (n = 70), and healthy normal controls (n = 39). To retain a broad spectrum of metabolites, we performed technically distinct analyses (global metabolomic profiling using LC-QTOFMS and targeted analyses using LC-MS/MS). Results: Higher levels of IL-6 and C-reactive protein and St. George Respiratory Questionnaire scores were seen in the T-COPD group, compared to those in the S-COPD group. Global metabolomic profiling showed elevated metabolites, including arachidonic and eicosanoic acids, in the T-COPD group. Typical changes in tryptophan catabolism were observed through targeted profiling. Additionally, in the T-COPD group, kynurenine was elevated, and serotonin levels were reduced; therefore, indoleamine dioxygenase (IDO)/tryptophan hydroxylase (TPH) activities were dysregulated. Correlation analyses showed that changes in oxylipins were positively correlated with serum levels of IL-6 and C-reactive protein. Conclusion: Patients with TB-related COPD have enhanced inflammatory responses that may be linked to fatty acid pathways and tryptophan catabolism, which could be novel therapeutic targets for T-COPD.

Keywords: biomarker; chronic obstructive pulmonary disease; metabolomics; smoking; tuberculosis.