Abstract
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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Adamko DJ, Sykes BD, Rowe BH . The metabolomics of asthma: novel diagnostic potential. Chest 2012; 141: 1295–302.
Leung TF, Ko FW, Wong GW . Recent advances in asthma biomarker research. Ther Adv Respir Dis 2013; 7: 297–308.
Carraro S, Giordano G, Reniero F, Carpi D, Stocchero M, Sterk PJ, et al. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy 2013; 68: 110–7.
Holgate ST . Pathogenesis of asthma. Clin Exp Allergy 2008; 38: 872–97.
Green RH, Brightling CE, Bradding P . The reclassification of asthma based on subphenotypes. Curr Opin Allergy Clin Immunol 2007; 7: 43–50.
Holgate ST . The airway epithelium is central to the pathogenesis of asthma. Allergol Int 2008; 57: 1–10.
Fixman ED, Stewart A, Martin JG . Basic mechanisms of development of airway structural changes in asthma. Eur Respir J 2007; 29: 379–89.
Saude EJ, Skappak CD, Regush S, Cook K, Ben-Zvi A, Becker A, et al. Metabolomic profiling of asthma: diagnostic utility of urine nuclear magnetic resonance spectroscopy. J Allergy Clin Immunol 2011; 127: 757–64.
Atzei A, Atzori L, Moretti C, Barberini L, Noto A, Ottonello G, et al. Metabolomics in paediatric respiratory diseases and bronchiolitis. J Matern Fetal Neonatal Med 2011; 24: 59–62.
Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc 2011; 6: 1060–83.
Fatemi F, Sadroddiny E, Gheibi A, Mohammadi Farsani T, Kardar GA . Biomolecular markers in assessment and treatment of asthma. Respirology 2014; 19: 514–23.
Carraro S, Rezzi S, Reniero F, Heberger K, Giordano G, Zanconato S, et al. Metabolomics applied to exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med 2007; 175: 986–90.
Fiehn O . Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comp Funct Genomics 2001; 2: 155–68.
Snowden S, Dahlen SE, Wheelock CE . Application of metabolomics approaches to the study of respiratory diseases. Bioanalysis 2012; 4: 2265–90.
Nicholson JK, Connelly J, Lindon JC, Holmes E . Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 2002; 1: 153–61.
Bogdanov M, Matson WR, Wang L, Matson T, Saunders-Pullman R, Bressman SS, et al. Metabolomic profiling to develop blood biomarkers for Parkinson's disease. Brain 2008; 131: 389–96.
Saito K, Matsuda F . Metabolomics for functional genomics, systems biology, and biotechnology. Annu Rev Plant Biol 2010; 61: 463–89.
Wu H, Liu T, Ma C, Xue R, Deng C, Zeng H, et al. GC/MS-based metabolomic approach to validate the role of urinary sarcosine and target biomarkers for human prostate cancer by microwave-assisted derivatization. Anal Bioanal Chem 2011; 401: 635–46.
Sofia M, Maniscalco M, de Laurentiis G, Paris D, Melck D, Motta A . Exploring airway diseases by NMR-based metabonomics: a review of application to exhaled breath condensate. J Biomed Biotechnol 2011; 2011: 403260.
Motta A, Paris D, D'Amato M, Melck D, Calabrese C, Vitale C, et al. NMR metabolomic analysis of exhaled breath condensate of asthmatic patients at two different temperatures. J Proteome Res 2014; 13: 6107–20.
Ubhi BK, Riley JH, Shaw PA, Lomas DA, Tal-Singer R, MacNee W, et al. Metabolic profiling detects biomarkers of protein degradation in COPD patients. Eur Respir J 2012; 40: 345–55.
Jung J, Kim SH, Lee HS, Choi GS, Jung YS, Ryu DH, et al. Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin Exp Allergy 2013; 43: 425–33.
Mattarucchi E, Baraldi E, Guillou C . Metabolomics applied to urine samples in childhood asthma; differentiation between asthma phenotypes and identification of relevant metabolites. Biomed Chromatogr 2012; 26: 89–94.
Wetmore DR, Joseloff E, Pilewski J, Lee DP, Lawton KA, Mitchell MW, et al. Metabolomic profiling reveals biochemical pathways and biomarkers associated with pathogenesis in cystic fibrosis cells. J Biol Chem 2010; 285: 30516–22.
Qiu Y, Cai G, Su M, Chen T, Zheng X, Xu Y, et al. Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res 2009; 8: 4844–50.
Chen T, Xie G, Wang X, Fan J, Qiu Y, Zheng X, et al. Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma. Mol Cell Proteomics 2011; 10: M110.004945.
Kind T, Wohlgemuth G, Lee do Y, Lu Y, Palazoglu M, Shahbaz S, et al. FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Anal Chem 2009; 81: 10038–48.
Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 2011; 12: 77.
Mukherjee AB, Zhang Z . Allergic asthma: influence of genetic and environmental factors. J Biol Chem 2011; 286: 32883–9.
Wheelock CE, Goss VM, Balgoma D, Nicholas B, Brandsma J, Skipp PJ, et al. Application of 'omics technologies to biomarker discovery in inflammatory lung diseases. Eur Respir J 2013; 42: 802–25.
Lisec J, Schauer N, Kopka J, Willmitzer L, Fernie AR . Gas chromatography mass spectrometry-based metabolite profiling in plants. Nat Protoc 2006; 1: 387–96.
Nordstrom A, Lewensohn R . Metabolomics: moving to the clinic. J Neuroimmune Pharmacol 2010; 5: 4–17.
Lloyd AJ, Beckmann M, Fave G, Mathers JC, Draper J . Proline betaine and its biotransformation products in fasting urine samples are potential biomarkers of habitual citrus fruit consumption. Br J Nutr 2011; 106: 812–24.
Walsh MC, Brennan L, Malthouse JP, Roche HM, Gibney MJ . Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans. Am J Clin Nutr 2006; 84: 531–9.
Pechlivanis A, Kostidis S, Saraslanidis P, Petridou A, Tsalis G, Mougios V, et al. 1H NMR-based metabonomic investigation of the effect of two different exercise sessions on the metabolic fingerprint of human urine. J Proteome Res 2010; 9: 6405–16.
Amaral AF . Metabolomics of asthma. J Allergy Clin Immunol 2014; 133: 1497–9.
Loureiro CC, Duarte IF, Gomes J, Carrola J, Barros AS, Gil AM, et al. Urinary metabolomic changes as a predictive biomarker of asthma exacerbation. J Allergy Clin Immunol 2014; 133: 261–3.
Fitzpatrick AM, Park Y, Brown LA, Jones DP . Children with severe asthma have unique oxidative stress-associated metabolomic profiles. J Allergy Clin Immunol 2014; 133: 258–61.
Eltzschig HK . Adenosine: an old drug newly discovered. Anesthesiology 2009; 111: 904–15.
da Rocha Lapa F, de Oliveira AP, Accetturi BG, de Oliveira Martins I, Domingos HV, de Almeida Cabrini D, et al. Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors. Purinergic Signal 2013; 9: 325–36.
McClay JL, Adkins DE, Isern NG, O'Connell TM, Wooten JB, Zedler BK, et al. 1H Nuclear magnetic resonance metabolomics analysis identifies novel urinary biomarkers for lung function. J Proteome Res 2010; 9: 3083–90.
Bronte V, Zanovello P . Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 2005; 5: 641–54.
Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, et al. Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 2010; 138: 682–92.
Hatziagorou E, Tsanakas J . Assessment of airway inflammation with exhaled NO measurement. Hippokratia 2007; 11: 51–62.
Acknowledgements
This study was supported by the Special Fund of the Chinese Medical Association for the Scientific Research of Chronic Respiratory Tract Diseases (07010440052) and National Natural Science Foundation of China-Youth Fund Project (81400017). We are grateful to Dr Yu TANG and Mr Jun-liang DENG (Biotree Bio-technology Co, Ltd, Shanghai, China) for providing help with the data analysis.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chang, C., Guo, Zg., He, B. et al. Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis. Acta Pharmacol Sin 36, 1356–1366 (2015). https://doi.org/10.1038/aps.2015.102
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2015.102
Keywords
This article is cited by
-
Association of lower plasma citric acid with prolonged cough: the Nagahama study
Scientific Reports (2023)
-
Metabolomics of bronchoalveolar lavage in children with persistent wheezing
Respiratory Research (2022)
-
Effects of carbon black nanoparticles and high humidity on the lung metabolome in Balb/c mice with established allergic asthma
Environmental Science and Pollution Research (2022)
-
Histological chorioamnionitis is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks
BMC Pediatrics (2021)
-
Characteristics of serum metabolites in sporadic amyotrophic lateral sclerosis patients based on gas chromatography-mass spectrometry
Scientific Reports (2021)
