High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children

Park, Youngja; Fitzpatrick, Anne M.; Medriano, Carl Angelo; Jones, Dean P.

doi:10.1016/j.jaci.2016.08.018

Cited by 42 publications

(39 citation statements)

References 40 publications

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“…Metabolomics has also helped to establish candidate biomarkers for asthma severity and steroid resistance [94]. However, additional studies are needed to standardize the approach to metabolomics in asthma.…”

Section: Rna Transcriptomics (Study Of Gene Expression)mentioning

confidence: 99%

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla

Lee

2018

Clinic Rev Allerg Immunol

832

719

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The model of asthma as a single entity has now been replaced by a much more complex biological network of distinct and interrelating inflammatory pathways. The term asthma is now considered an umbrella diagnosis for several diseases with distinct mechanistic pathways (endotypes) and variable clinical presentations (phenotypes). The precise definition of these endotypes is central to asthma management due to inherent therapeutic and prognostic implications. This review presents the molecular mechanisms behind the heterogeneity of airway inflammation in asthmatic patients. Asthma endotypes may be broadly regarded as type 2 (T2) high or T2-low. Several biologic agents have been approved for T2-high asthma, with numerous other therapeutics that are incipient and similarly targeted at specific molecular mechanisms. Collectively, these advances have shifted existing paradigms in the approach to asthma to tailor novel therapies.

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Section: Rna Transcriptomics (Study Of Gene Expression)mentioning

confidence: 99%

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla

Lee

2018

Clinic Rev Allerg Immunol

832

719

View full text Add to dashboard Cite

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“…Biomarkers can be used to diagnose and understand disease pathophysiology. Previous studies confirmed numerous metabolite‐specific pathways related to immune responses and oxidative stress, and dysfunctional carbohydrate, amino acid, bile acid, steroid, nucleotide and lipid metabolism related to asthma . Inflammation and aberrant immune responses are characteristic features of all asthmatic phenotypes.…”

Section: Discussionmentioning

confidence: 65%

“…To date, no study has confirmed the precise value of single biomarker approaches, such as using F E NO or peripheral blood eosinophilia, to diagnose childhood asthma. Because any single biomarker for asthma may lack sensitivity, specificity, stability and manoeuvrability, various indicators including combinations of metabolites have been increasingly assessed for diagnosing asthma and its subtypes . A previous study demonstrated that PLS‐DA model on nuclear magnetic resonance data distinguished asthma and its subtypes with >90% accuracy .…”

Section: Discussionmentioning

confidence: 99%

Urine metabolic profiles in paediatric asthma

et al. 2019

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Background and objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology. Methods: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes. Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma. Conclusion: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.We investigated metabolic profiles of paediatric asthma patients to identify asthma-specific biomarkers in urine. A combination of eight metabolites showed excellent discrimination across groups. Enrichment analysis identified complex biological processes associated with immunity, inflammation, oxidative stress and DNA damage. These approaches enabled discrimination between asthma stages and elucidate its mechanisms.

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“…Metabolomics studies comparing asthmatics and healthy controls are useful to identify altered metabolic pathways and to expand our knowledge about the disease pathophysiology. Metabolomics can be also useful for clinical practice, such as evaluating consequences and the effect of a specific treatment or giving insights about altered pathways in treatment-resistant subjects and encourage the development of new target therapies (18,19,22,(31)(32)(33)(34). Metabolomics can also be used to differentiate asthma among other airway diseases, such as chronic obstructive pulmonary disease (35).…”

Section: Research and Clinical Valuementioning

confidence: 99%

Metabolic interactions in asthma

Farraia

Rufo

Paciência

et al. 2019

Eur Ann Allergy Clin Immunol

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Metabolomics can be used to explore altered metabolic pathways in asthma, giving insights into its pathophysiology. We aimed to review how metabolomics has been used to understand asthma by describing metabolic pathways under research and discussing clinical implications. The search was performed in PubMed, and studies published since 2000 using a metabolomics approach, were included. A total of 32 studies were analysed. Pathways related with cellular energy homeostasis, lipid metabolism and oxidative stress, immune and inflammatory processes and others were altered. Initial studies focused on biomarker discovery. But metabolomics can be used to evaluate drug effects on specific pathways, to highlight pathways that can further develop in new targeted treatments, and to identify differences according to asthma severity and phenotypes.Abbreviations BALF, bronchoalveolar lavage fluid; CS, corticosteroid; EBC, exhaled breath condensate; GCxGC-TOF/MS, two-dimensional gas chromatography with time-of-flight mass spectrom-

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High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children

Cited by 42 publications

References 40 publications

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Urine metabolic profiles in paediatric asthma

Metabolic interactions in asthma

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