Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with <scp>COPD</scp>

Kim, Chang-Hwan; Ko, Yousang; Kim, Suhee; Yoo, Hyun Ju; Lee, Jae Seung; Rhee, Chin Kook; Lee, Jin Hwa; Lee, Ji Hyun; Kim, Tae Hyung; Lim, Seong Yong; Yoo, Kwang Ha; Seo, Joon Beom; Oh, Yeon Mok; Lee, Sang Do; Park, Young Bum

doi:10.1111/resp.13170

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…Not surprisingly, desmosine has been identified as a potential biomarker for structural lung injury in pulmonary TB and chronic obstructive pulmonary disease. 47,48 Overall, we propose that the metabolites here constitute a data subset indicative of alveolar destruction (Figure 2), progressive proteolysis, and establishment of lung fibrosis 49,50 occurring during TB progression.…”

Section: Tb Disease Progression Correlates With An Increase In Proteo...mentioning

confidence: 78%

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach

et al. 2020

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The mechanisms whereby Mycobacterium tuberculosis (Mtb) rewires the host metabolism in vivo are surprisingly unexplored. Here, we used three high-resolution mass spectrometry platforms to track altered lung metabolic changes associated with Mtb infection of mice. The multiplatform data sets were merged using consensus orthogonal partial least squares-discriminant analysis (cOPLS-DA), an algorithm that allows for the joint interpretation of the results from a single multivariate analysis. We show that Mtb infection triggers a temporal and progressive catabolic state to satisfy the continuously changing energy demand to control infection. This causes dysregulation of metabolic and oxido-reductive pathways culminating in Mtb-associated wasting. Notably, high abundances of trimethylamine-N-oxide (TMAO), produced by the host from the bacterial metabolite trimethylamine upon infection, suggest that Mtb could exploit TMAO as an electron acceptor under anaerobic conditions. Overall, these new pathway alterations advance our understanding of the link between Mtb pathogenesis and metabolic dysregulation and could serve as a foundation for new therapeutic intervention strategies. Mass spectrometry data has been deposited in the Metabolomics Workbench repository (data-set identifier: ST001328).

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Section: Tb Disease Progression Correlates With An Increase In Proteo...mentioning

confidence: 78%

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach

et al. 2020

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“…In the previous study, urinary desmosine was reported to be a useful biomarker for identifying frequent exacerbators of COPD patients. 52 Besides, the upregulation of IL-1 pathway mediators (IRAK2, IRAK3, PELI1 and IL1R1) 53 was reported to be relevant to frequent exacerbations of COPD. Fu et al 54 demonstrated that serum IL-6 and sputum IL-1β were associated with the frequent exacerbations.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD

Liu

Xue

et al. 2018

COPD

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ObjectivesMicroRNAs (miRNAs) play essential roles in the development of COPD. In this study, we aimed to identify and validate potential miRNA biomarkers in frequent and non-frequent exacerbators of COPD patients using bioinformatic analysis.Materials and methodsThe candidate miRNA biomarkers in COPD were screened from Gene Expression Omnibus (GEO) dataset and identified using GEO2R online tool. Then, we performed bioinformatic analyses including target prediction, gene ontology (GO), pathway enrichment analysis and construction of protein–protein interaction (PPI) network. Furthermore, the expression of the identified miRNAs in peripheral blood monocular cells (PBMCs) of COPD patients was validated using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsMiR-23a, miR-25, miR-145 and miR-224 were identified to be significantly downregulated in COPD patients compared with healthy controls. GO analysis showed the four miRNAs involved in apoptotic, cell differentiation, cell proliferation and innate immune response. Pathway analysis showed that the targets of these miRNAs were associated with p53, TGF-β, Wnt, VEGF and MAPK signal pathway. In healthy controls, the miR-25 and miR-224 levels were significantly decreased in smokers compared with nonsmokers (P<0.001 and P<0.05, respectively). In COPD patients, the levels of miR-23a, miR-25, miR-145 and miR-224 were associated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. Notably, miR-23a and miR-145 were significantly elevated in non-frequent exacerbators compared with frequent exacerbators (P<0.05), and miR-23a showed higher area under the receiver–operator characteristic curve (AUROC) than miR-145 (0.707 vs 0.665, P<0.05).ConclusionMiR-23a, miR-25, miR-145 and miR-224 were associated with the development of COPD, and miR-23a might be a potential biomarker for discriminating the frequent exacerbators from non-frequent exacerbators.

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“…Systemic arteries and the lung parenchyma may share high susceptibility to degradation of elastin and other components of the extracellular matrix [49]. In fact, desmosine, a specific biomarker of elastin degradation, has been associated with both emphysema and central arterial stiffness in COPD [50,51]. We cannot rule out the possibility that patients with mild COPD and greater emphysema burden were physically less active than their counterparts with less emphysema.…”

Section: Discussionmentioning

confidence: 93%

Systemic vascular dysfunction is associated with emphysema burden in mild COPD

Zelt

Jones

Hirai

et al. 2018

Respiratory Medicine

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Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with COPD

Abstract: This study indicates that the level of urinary desmosines measured by LC-MS/MS methods is associated with the CT emphysema index. Urinary desmosine can be a useful predictor in identifying frequent exacerbators.

Cited by 15 publications

References 26 publications

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach

Comprehensive Examination of the Mouse Lung Metabolome Following Mycobacterium tuberculosis Infection Using a Multiplatform Mass Spectrometry Approach

Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD

Systemic vascular dysfunction is associated with emphysema burden in mild COPD

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