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

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.