Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD

Ghosh, Nilanjana; Choudhury, Priyanka; Subramani, Elavarasan; Saha, Debasri; Sengupta, Sayoni; Banerjee, Rintu; Roychowdhury, Sushmita; Bhattacharyya, Parthasarathi; Chaudhury, Koel

doi:10.1007/s11306-019-1552-z

Cited by 33 publications

(25 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous reports on glucose down-regulation in COPD and asthma exist [22,41,42]. A similar trend was also observed in our previous NMR study where significant decrease in glucose level in ACO was observed [27]. Mannose is an intermediate metabolite of galactose metabolism pathway and may be converted to fructose-6-phosphate which enters the glycolytic pathway [43].…”

Section: Discussionsupporting

confidence: 78%

“…Our earlier findings using NMR metabolomics indicate an enhanced energy and metabolic burden associated with ACO as compared to asthma and COPD [27]. This motivates us to gain a deeper insight into inflammationrelated metabolism in ACO.…”

Section: Introductionmentioning

confidence: 84%

“…Notes: nsnot significant, * p ≤ 0.05, **p ≤ 0.01, **p ≤ 0.001, ****p ≤ 0.0001. Abbreviations: ACO-Asthma COPD overlap, COPD-Chronic obstructive pulmonary disease, TNF α-Tumor necrosis factor α, IL-1β-Interleukin 1β, GM-CSF-Granulocyte-macrophage colony-stimulating factor, NGAL-Neutrophil gelatinase-associated lipocalin, MCP 1-Monocyte Chemoattractant Protein-1, YKL 40-Chitinase-3-like protein 1, IFN γ-Interferon γ, TGF β-Transforming growth factor β Table 4 Pearson's correlation value (r) and significance values (p) depicting the extent to which the 13 dysregulated immunological mediators (significantly altered in ACO vs. asthma, ACO vs. COPD and ACO vs controls) are linearly related to FEV1 and FEV1/FVC of ACO subjects contributing to the higher mortality and morbidity in ACO in comparison to asthma/COPD [27]. Since MS is known to provide complementary information to NMR [18], serum metabolome of the same patients are analysed using GC-MS.…”

Section: Discussionmentioning

confidence: 99%

“…Written informed consent was obtained from all participants who volunteered to participate in this study. The detailed inclusion and exclusion criteria are discussed elsewhere [27]. Briefly, the recruited subjects were assigned to four groups: (a) moderate or severe cases of asthma, diagnosed based on the GINA guidelines (GINA 2014) [28] (b) stage II and III, i.e.…”

Section: Subject Selectionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Asthma-COPD overlap (ACO) refers to a group of poorly studied and characterised patients reporting with disease presentations of both asthma and COPD, thereby making both diagnosis and treatment challenging for the clinicians. They exhibit a higher burden in terms of both mortality and morbidity in comparison to patients with only asthma or COPD. The pathophysiology of the disease and its existence as a unique disease entity remains unclear. The present study aims to determine whether ACO has a distinct metabolic and immunological mediator profile in comparison to asthma and COPD. Methods: Global metabolomic profiling using two different groups of patients [discovery (D) and validation (V)] were conducted. Serum samples obtained from moderate and severe asthma [n = 34(D); n = 32(V)], moderate and severe COPD [n = 30(D); 32(V)], ACO patients [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using gas chromatography mass spectrometry (GC-MS). Multiplexed analysis of 25 immunological markers (IFN-γ (interferon gamma), TNF-α (tumor necrosis factor alpha), IL-12p70 (interleukin 12p70), IL-2, IL-4, IL-5, IL-13, IL-10, IL-1α, IL-1β, TGF-β (transforming growth factor), IL-6, IL-17E, IL-21, IL-23, eotaxin, GM-CSF (granulocyte macrophagecolony stimulating factor), IFN-α (interferon alpha), IL-18, NGAL (neutrophil gelatinase-associated lipocalin), periostin, TSLP (thymic stromal lymphopoietin), MCP-1 (monocyte chemoattractant protein-1), YKL-40 (chitinase 3 like 1) and IL-8) was also performed in the discovery cohort. Results: Eleven metabolites [serine, threonine, ethanolamine, glucose, cholesterol, 2-palmitoylglycerol, stearic acid, lactic acid, linoleic acid, D-mannose and succinic acid] were found to be significantly altered in ACO as compared with asthma and COPD. The levels and expression trends were successfully validated in a fresh cohort of subjects. Thirteen immunological mediators including TNFα, IL-1β, IL-17E, GM-CSF, IL-18, NGAL, IL-5, IL-10, MCP-1, YKL-40, IFNγ, IL-6 and TGF-β showed distinct expression patterns in ACO. These markers and metabolites exhibited significant correlation with each other and also with lung function parameters.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Subject Selectionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fortis et al showed that both the serum and urine metabolomic profiles showed marked differences between patients with stable COPD and those with AECOPD [ 42 ]. Additionally, Ghosh et al revealed that 12 differential metabolites in serum were dysregulated in patients with asthma-COPD overlap (ACO) compared with both patients with asthma and patients with COPD [ 51 ]. However, the association between the metabolomic profiles of induced sputum and COPD severity has not been previously studied.…”

Section: Discussionmentioning

confidence: 99%

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

Zhu

Wang

et al. 2020

EPMA Journal

View full text Add to dashboard Cite

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.

show abstract

Identification of novel metabolic signatures potentially involved in the pathogenesis of COPD associated pulmonary hypertension

et al. 2021

View full text Add to dashboard Cite

Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD

Cited by 33 publications

References 58 publications

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

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

Identification of novel metabolic signatures potentially involved in the pathogenesis of COPD associated pulmonary hypertension

Contact Info

Product

Resources

About