Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD

Cruickshank‐Quinn, Charmion; Jacobson, Sean; Hughes, Grant; Powell, Roger; Petrache, Irina; Kechris, Katerina; Bowler, Russell P.; Reisdorph, Nichole

doi:10.1038/s41598-018-35372-w

Cited by 72 publications

(77 citation statements)

References 82 publications

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“…A total of 11 metabolites and 13 inflammatory mediators were found to be important in distinguishing ACO from both asthma and COPD. Changes in plasma levels of glucogenic amino acids like serine and threonine have been reported by different groups in both asthma [23] and COPD [38,39]. Serine and threonine may get converted to pyruvate which in turn enters the TCA cycle to compensate the energy demand [40].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Metabolism. Lung epithelial cells exposed to cigarette smoking have shown a decrease in glycolysis but an increase in fatty acid oxidation, suggesting that metabolic dysregulation may regulate lung destruction and impaired repair in COPD (Agarwal et al, 2014;Jiang et al, 2017;Cruickshank-Quinn et al, 2018). Exposure of human lung fibroblast to cigarette smoke inhibits oxidative phosphorylation complex III (Lei et al, 2017).…”

Section: Wnt Pathway In Copdmentioning

confidence: 99%

Perspectives on Wnt Signal Pathway in the Pathogenesis and Therapeutics of Chronic Obstructive Pulmonary Disease

Gao

et al. 2019

J Pharmacol Exp Ther

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Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with progressive airflow limitation and functional decline. The pathogenic mechanisms for this disease include oxidative stress, inflammatory responses, disturbed protease/antiprotease equilibrium, apoptosis/proliferation imbalance, senescence, autophagy, metabolic reprogramming, and mitochondrial dysfunction. The Wnt signaling pathway is an evolutionarily conserved signaling pathway that is abnormal in COPD, including chronic bronchitis and pulmonary emphysema. Furthermore, Wnt signaling has been shown to modulate aforementioned cellular processes involved in COPD. From this perspective, we provide an updated understanding of the crosstalk between Wnt signal and these cellular processes, and highlight the crucial role of the Wnt signal during the development of COPD. We also discuss the potential for targeting the Wnt signal in future translational and pharmacological therapeutics aimed at prevention and treatment of this disease.

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“…Metabolomics, the simultaneous assessment of multiple small molecules usually combining liquid chromatography with mass spectrometry, is being increasingly employed in blood samples in large COPD studies [95,96]. Exhaled breath condensate is a promising noninvasive sample for COPD metabolomics [97].…”

Section: Other Omics Technologies In Copd Pharmacogenomicsmentioning

confidence: 99%

Pharmacogenomics of chronic obstructive pulmonary disease

Hersh

2019

Expert Review of Respiratory Medicine

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Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, which presents the opportunity for precision therapy based on genetics or other biomarkers. Areas covered: Alpha-1 antitrypsin deficiency, a genetic form of emphysema, provides an example of this precision approach to diagnosis and therapy. To date, research in COPD pharmacogenomics has been limited by small sample sizes, lack of accessible target tissue, failure to consider COPD subtypes, and different outcomes relevant for various medications. There have been several published genome-wide association studies and other omics studies in COPD pharmacogenomics; however, clinical implementation remains far away. There is a growing evidence base for precision prescription of inhaled corticosteroids in COPD, based on clinical phenotypes and blood biomarkers, but not yet based on pharmacogenomics. Expert opinion: At this time, there is insufficient evidence for clinical implementation of COPD pharmacogenomics. Additional genome-wide studies will be required to discover predictors of drug response and to identify genomic biomarkers of COPD subtypes, which could be targeted with subtype-directed therapies.

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Metabolomics and transcriptomics pathway approach reveals outcome-specific perturbations in COPD

Cited by 72 publications

References 82 publications

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

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

Perspectives on Wnt Signal Pathway in the Pathogenesis and Therapeutics of Chronic Obstructive Pulmonary Disease

Pharmacogenomics of chronic obstructive pulmonary disease

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