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

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.

Metabolomic profiling of lung function in Costa-Rican children with asthma

“…Pre- and post-bronchodilator FEV 1 /FVC showed almost identical metabolomic signatures; the majority of the constituent metabolites were amines, a metabolite class consistently linked with asthma [18–20]. Thiamine, which can trigger allergic reactions [21], and creatinine, a break down product of creatine which exacerbates lung inflammation [22], were among the top metabolites for all three outcomes.…”

“…Three pathways, relating to lipid and nucleotide metabolism, were enriched among the metabolites identified as significantly associated with all three asthma endpoints. A number of these pathways and their constituent metabolites have been previously associated with asthma endpoints [20, 26–28]. It is hypothesized they may be involved in the overall asthmatic phenotype through broad mechanisms such as the mediation of the inflammatory response, oxidative stress and alterations in the cellular energy requirements of activated inflammatory cells.…”

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

“…20 The highest AUC for a single metabolite was 0.976 for succinate in serum. 19 On the basis of these studies, there was no evidence that including larger numbers of metabolites in the profile increased discriminatory ability.…”

“…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.…”

“…In the search for biomarkers several possible validation strategies can be used, including: (1) testing on a separately recruited and ascertained validation cohort; (2) using a hold-out data set; and (3) performing permutation testing by label shuffling. 24,25 Eight 5,7,8,14,15,17,19,21 and four 9,12,13,20 studies used permutation and a hold-out dataset, respectively. Both approaches provided support for accuracy of the reported biomarkers.…”