Metabolomic Endotype of Asthma

Comhair, Suzy; McDunn, Jonathan E.; Bennett, Carole; Fettig, Jade; Erzurum, Serpil C.; Kalhan, Satish C.

doi:10.4049/jimmunol.1500736

Cited by 115 publications

(135 citation statements)

References 42 publications

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“…C omhair et al. [12] also found suppression of plasma steroids in patients with severe asthma in a metabolomics study. To our knowledge, however, reduced ProHyp and pipecolic acid have not been reported previously in association with therapeutic corticosteroids administration.…”

Section: Discussionmentioning

confidence: 98%

Metabolomics analysis identifies different metabotypes of asthma severity

et al. 2017

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In this study, we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity.We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild, 20 moderate, 22 severe) using liquid chromatography–high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids, sphingolipids and free fatty acids.We conclusively identified 66 metabolites; 15 were significantly altered with asthma (p≤0.05). Levels of dehydroepiandrosterone sulfate, cortisone, cortisol, prolylhydroxyproline, pipecolate and N-palmitoyltaurine correlated significantly (p<0.05) with inhaled corticosteroid dose, and were further shifted in individuals treated with oral corticosteroids. Oleoylethanolamide increased with asthma severity independently of steroid treatment (p<0.001). Multivariate analysis revealed two patterns: 1) a mean difference between controls and patients with mild asthma (p=0.025), and 2) a mean difference between patients with severe asthma and all other groups (p=1.7×10−4). Metabolic shifts in mild asthma, relative to controls, were associated with exogenous metabolites (e.g. dietary lipids), while those in moderate and severe asthma (e.g. oleoylethanolamide, sphingosine-1-phosphate, N-palmitoyltaurine) were postulated to be involved in activating the transient receptor potential vanilloid type 1 (TRPV1) receptor, driving TRPV1-dependent pathogenesis in asthma.Our findings suggest that asthma is characterised by a modest systemic metabolic shift in a disease severity-dependent manner, and that steroid treatment significantly affects metabolism.

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Section: Discussionmentioning

confidence: 98%

Metabolomics analysis identifies different metabotypes of asthma severity

et al. 2017

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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%

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

Kelly

Dahlin

McGeachie

et al. 2017

Chest

149

135

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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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“…Metabolomics, the comprehensive analysis of small biochemicals in biological systems, can provide insight into complex biochemical processes and enable the identification of biomarkers that may serve as therapeutic targets [18]. Successful applications of the metabolomic approach have been located at active herb molecules, single herb preparations, and multiple herb derived prescriptions [19,20].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations

Meng

Jia

et al. 2017

IJMS

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Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares-discriminate analysis (PLS−DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (L3 or P2), sphinganine (L6 or P4), and lysoPC(15:0) (L12 or P16) were detected both in lung tissue and plasma. Additionally, L-acetylcarnitine (L1), thromboxane B2 (L2), 10-HDoHE (L10), and 5-HETE (L11) were first reported to be potential biomarkers associated with allergic asthma. The treatment of mKG mediated all of those potential biomarkers except lysoPC(15:0) (P16). The anti-asthma mechanism of mKG can be achieved through the comprehensive regulation of multiple perturbed biomarkers and metabolic pathways.

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Metabolomic Endotype of Asthma

Cited by 115 publications

References 42 publications

Metabolomics analysis identifies different metabotypes of asthma severity

Metabolomics analysis identifies different metabotypes of asthma severity

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

The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations

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