Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations

Cottrill, Kirsten A.; Stephenson, Susan; Mohammad, Ahmad F.; Kim, Susan O; McCarty, Nael A.; Kamaleswaran, Rishikesan; Fitzpatrick, Anne M.; Chandler, Joshua D.

doi:10.1016/j.jaci.2022.07.027

Cited by 11 publications

(12 citation statements)

References 64 publications

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“…M2 macrophages bear a high level of ARG1 expression, and the enzyme is considered to be the main consumer of L-Arg in vivo, because the arginases-coupled reaction rate (Vmax) is 1000 times greater than the eNOS-coupled one [ 43 ]. Accordingly, Matysiak et al [ 44 ] found that patients with bronchial asthma had decreased their L-Arg level in the peripheral blood, as confirmed additionally by Cottrill et al in a study of children suffering from bronchial asthma [ 45 ]. Moreover, the level of L-Arg in children, prone to exacerbations, was lower than in those with controlled bronchial asthma.…”

Section: L-arginine Metabolism In Pathogenesis Of Bronchial Asthma An...mentioning

confidence: 83%

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Старикова

Rubinstein

Mammedova

et al. 2023

CIMB

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More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches.

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Section: L-arginine Metabolism In Pathogenesis Of Bronchial Asthma An...mentioning

confidence: 83%

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Старикова

Rubinstein

Mammedova

et al. 2023

CIMB

View full text Add to dashboard Cite

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“…Two studies investigated the relationship between the endotype and the pattern of symptoms , analyzing the frequency of exacerbations and wheezing. Cottrill et al [ 28 ] applied a mass spectrometry (MS)-based metabolomic approach to search for a metabolomic profile (metabotype) associated with the clinical phenotype characterized by frequent exacerbations (i.e., three or more exacerbations per year). The authors found that children with exacerbation-prone asthma could be discriminated on the base of their blood metabolomic profile, which showed perturbations in the pathways of arginine, lysine and methionine.…”

Section: Resultsmentioning

confidence: 99%

Metabolomics Applied to Pediatric Asthma: What Have We Learnt in the Past 10 Years?

Ferraro,

Zanconato,

Carraro

2023

Children

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Background: Asthma is the most common chronic condition in children. It is a complex non-communicable disease resulting from the interaction of genetic and environmental factors and characterized by heterogeneous underlying molecular mechanisms. Metabolomics, as with the other omic sciences, thanks to the joint use of high-throughput technologies and sophisticated multivariate statistical methods, provides an unbiased approach to study the biochemical–metabolic processes underlying asthma. The aim of this narrative review is the analysis of the metabolomic studies in pediatric asthma published in the past 10 years, focusing on the prediction of asthma development, endotype characterization and pharmaco-metabolomics. Methods: A total of 43 relevant published studies were identified searching the MEDLINE/Pubmed database, using the following terms: “asthma” AND “metabolomics”. The following filters were applied: language (English), age of study subjects (0–18 years), and publication date (last 10 years). Results and Conclusions: Several studies were identified within the three areas of interest described in the aim, and some of them likely have the potential to influence our clinical approach in the future. Nonetheless, further studies are needed to validate the findings and to assess the role of the proposed biomarkers as possible diagnostic or prognostic tools to be used in clinical practice.

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“…A study found that genes associated with lysine levels may be also linked to reduced inflammation and the degradation of air pollutants, and that these genes are less abundant in asthmatics [ 21 ]. Furthermore, there are differences in serum metabolites between children with exacerbation-prone and non-exacerbation-prone asthma, with significant differences in those from the lysine pathway [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

A prognosis prediction chromatin regulator signature for patients with severe asthma

Gao¹,

Chen²,

Li³

et al. 2023

Allergy Asthma Clin Immunol

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Severe asthma imposes a physical and economic burden on both patients and society. As chromatin regulators (CRs) influence the progression of multiple diseases through epigenetic mechanisms, we aimed to study the role of CRs in patients with severe asthma. Transcriptome data (GSE143303) from 47 patients with severe asthma and 13 healthy participants was downloaded from the Gene Expression Omnibus database. Enrichment analysis was performed to investigate the functions of differentially expressed CRs between the groups. We identified 80 differentially expressed CRs; they were mainly enriched in histone modification, chromatin organization, and lysine degradation. A protein–protein interaction network was then constructed. The analyzed immune scores were different between sick and healthy individuals. Thus, CRs with a high correlation in the immune analysis, SMARCC1, SETD2, KMT2B, and CHD8, were used to construct a nomogram model. Finally, using online prediction tools, we determined that lanatoside C, cefepime, and methapyrilene may be potentially effective drugs in the treatment of severe asthma. The nomogram constructed using the four CRs, SMARCC1, SETD2, KMT2B, and CHD8, may be a useful tool for predicting the prognosis of patients with severe asthma. This study provided new insights into the role of CRs in severe asthma.

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Exacerbation-prone pediatric asthma is associated with arginine, lysine, and methionine pathway alterations

Cited by 11 publications

References 64 publications

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

Metabolomics Applied to Pediatric Asthma: What Have We Learnt in the Past 10 Years?

A prognosis prediction chromatin regulator signature for patients with severe asthma

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