Urinary metabolomic changes as a predictive biomarker of asthma exacerbation

Loureiro, Cláudia Chaves; Duarte, Iola F.; Gomes, J. M.; Carrola, Joana; Barros, António S.; Gil, Ana M.; Bousquet, Jean; Todo-Bom, Ana; Rocha, Sı́lvia M.

doi:10.1016/j.jaci.2013.11.004

Cited by 57 publications

(47 citation statements)

References 9 publications

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“…However, we did not detect changes in aldehydes and alkanes, which were demonstrated in urinary metabolic profiles to be linked to asthma exacerbation by GC-MS in other studies [37] . Moreover, our results did not show unique oxidative stress-associated metabolomics profiles, such as those reported for children with severe asthma [38] .…”

Section: Discussioncontrasting

confidence: 88%

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Chang

Guo

et al. 2015

Acta Pharmacol Sin

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Aim: To character the specific metabolomics profiles in the sera of Chinese patients with mild persistent asthma and to explore potential metabolic biomarkers. Methods: Seventeen Chinese patients with mild persistent asthma and age-and sex-matched healthy controls were enrolled. Serum samples were collected, and serum metabolites were analyzed using GC-MS coupled with a series of multivariate statistical analyses. Results: Clear intergroup separations existed between the asthmatic patients and control subjects. A list of differential metabolites and several top altered metabolic pathways were identified. The levels of succinate (an intermediate in tricarboxylic acid cycle) and inosine were highly upregulated in the asthmatic patients, suggesting a greater effort to breathe during exacerbation and hypoxic stress due to asthma. Other differential metabolites, such as 3,4-dihydroxybenzoic acid and phenylalanine, were also identified. Furthermore, the differential metabolites possessed higher values of area under the ROC curve (AUC), suggesting an excellent clinical ability for the prediction of asthma. Conclusion: Metabolic activity is significantly altered in the sera of Chinese patients with mild persistent asthma. The data might be helpful for identifying novel biomarkers and therapeutic targets for asthma.

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Section: Discussioncontrasting

confidence: 88%

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Chang

Guo

et al. 2015

Acta Pharmacol Sin

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“…Glycine is a non-essential amino acid that plays an essential role in metabolism homeostasis in patients with asthma [31]. Creatine interplays with glycine and serine and represents a major metabolic crossroad that links several biological pathways [32].…”

Section: Discussionmentioning

confidence: 99%

“…Previous metabolomics studies revealed metabolic alteration in the asthma exacerbated condition [32,[34][35][36]. Histidine, trimethylamine N-oxide, phenylacetylglycine, threonine, 4-aminohippurate and methylamine were decreased, whereas creatine, glucose, hippurate, alanine, glycolate, succinate, myo-inositol, dimethylamine, formate, homovanillate, acetylcarnitine, taurine, lactate, oxaloacetate, cis-aconitate, 2-methylglutarate, tyrosine, 1-methylhistamine, 2-hydroxyisobutyrate, acetone, carnitine, 3-methyladipate and 2-oxoglutarate were increased in asthmatic children during acute exacerbation.…”

Section: Discussionmentioning

confidence: 99%

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation

Yang

Zhang

et al. 2017

Basic Clin Pharma Tox

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Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic reprogramming associated with a combination treatment of inhaled budesonide and salbutamol in asthmatic children.Glucocorticoids and beta2 agonists represent the most important and frequently used drugs for symptom control in asthmatic children during acute exacerbation [1,2]. Current guidelines recommend the combined use of glucocorticoids and beta2 agonists as the preferred therapy for asthmatic children during acute exacerbation [3,4]. The glucocorticoid and beta2 agonist therapies are effective at controlling airway inflammation, reducing asthma symptoms, decreasing airway hyper-responsiveness and reducing the frequency and severity of exacerbations as well as asthma mortality. Despite their undoubted effectiveness and safety, there is still no consensus about the resulting metabolic derangements, including the development of dyslipidaemia, insulin resistance, glucose intolerance, diabetes, central adiposity and skeletal muscle wasting [5][6][7].Both glucocorticoids and beta2 agonists have the potential to influence glucose, lipid and protein...

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“…Twenty-one studies using metabolomic profiling of exhaled breathe condensate (EBC) (n ¼ 11), [3][4][5][6][7][8][9][10][11][12][13] urine (n ¼ 4), [14][15][16][17] serum (n ¼ 3), [18][19][20] and plasma (n ¼ 3) [21][22][23] were identified (Table 1). Twelve studies evaluated children, [3][4][5][6][7][8][9][10]14,15,21,22 eight evaluated adults, 12,13,[16][17][18][19][20]23 and one included both. 11 The majority used MS-based methods; six used NMR.…”

Section: Methodsmentioning

confidence: 99%

“…11 The majority used MS-based methods; six used NMR. [10][11][12][13]15,20 All but four 16,17,21,22 were case-control in design, and the total number of people with asthma ranged from 10 16 to 343. 9 The primary aim of most studies was to examine the differences between asthma cases and healthy control patients, with a smaller number of studies examining disease severity or phenotypes.…”

Section: Methodsmentioning

confidence: 99%

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic

Kelly

Dahlin

McGeachie

et al. 2017

Chest

147

120

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Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age. In particular, acetate, adenosine, alanine, hippurate, succinate, threonine, and trans-aconitate, and pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were all identified as significant in at least two studies. There were also a number of nonreplicated results; however, the literature is not yet sufficiently developed to determine whether these represent spurious findings or reflect the substantial heterogeneity and limited statistical power in the studies and their methods to date. This review highlights the need for additional asthma metabolomic studies to explore these issues, and, further, the need for standardized methods in the way these studies are conducted. We conclude by discussing the potential of translation of these metabolomic findings into clinically useful biomarkers and the crucial role that integrated omics is likely to play in this endeavor.CHEST 2017; 151(2):262-277

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Urinary metabolomic changes as a predictive biomarker of asthma exacerbation

Cited by 57 publications

References 9 publications

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic

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