ArticlePloS one2017
Arginine metabolic endotypes related to asthma severity.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of Novel Biomarkers for Evaluating Disease Severity in House-Dust-Mite-Induced Allergic Rhinitis by Serum Metabolomics.Disease markers · 2021Trial
- l-Arginine supplementation in severe asthma.JCI insight · 2020Trial
- Comparative analysis of amino acid profiles across pediatric groups stratified by asthma and IgE-dependent allergy showed differences in serum asparagine levels.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Fueling asthma inflammation via bioenergetic metabolic reprogramming.Redox biology · 2026Article
- Glycolytic reprogramming and cell-specific lactylation in asthma: an evidence-graded framework for testable metabolic-epigenetic profiles.Frontiers in immunology · 2026Review
- Biochemistry, pharmacology, and in vivo function of arginases.Pharmacological reviews · 2025Review
- Plasma lipids, amino acids, and their metabolic pathways as potential biomarkers for differential diagnosis of cold and heat syndrome asthma in children: a preliminary study.Frontiers in pediatrics · 2025Article
- Calcium Signaling in Airway Epithelial Cells: Current Understanding and Implications for Inflammatory Airway Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Metabolomics in Animal Models of Bronchial Asthma and Its Translational Importance for Clinics.International journal of molecular sciences · 2023Review
- Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Immune Metabolism in TH2 Responses: New Opportunities to Improve Allergy Treatment - Disease-Specific Findings (Part 1).Current allergy and asthma reports · 2023Review
- Differences in L-arginine metabolism and asthma morbidity among asthma patients with and without obstructive sleep apnea.Respiratory research · 2022Article
- Metabolomics in asthma: A platform for discovery.Molecular aspects of medicine · 2022Review
- The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: An overview of Network organization, procedures, and interventions.The Journal of allergy and clinical immunology · 2022Review
- Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease.Frontiers in immunology · 2022Article
- Pharmaco-Metabolomics of Inhaled Corticosteroid Response in Individuals with Asthma.Journal of personalized medicine · 2021Article
- Asthma and Three Colinear Comorbidities: Obesity, OSA, and GERD.The journal of allergy and clinical immunology. In practice · 2021Review
- Research Progress of Metabolomics in Asthma.Metabolites · 2021Review
- Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation.The European respiratory journal · 2021Review
- Potential Metabolic Biomarkers in Adult Asthmatics.Metabolites · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsArginine metabolism via inducible nitric oxide synthase (iNOS) and arginase 2 (ARG2) is higher in asthmatics than in healthy individuals. We hypothesized that a sub-phenotype of asthma might be defined by the magnitude of arginine metabolism categorized on the basis of high and low fraction of exhaled nitric oxide (FENO).
methodsTo test this hypothesis, asthmatics (n = 52) were compared to healthy controls (n = 51) for levels of FENO, serum arginase activity, and airway epithelial expression of iNOS and ARG2 proteins, in relation to clinical parameters of asthma inflammation and airway reactivity. In parallel, bronchial epithelial cells were evaluated for metabolic effects of iNOS and ARG2 expression in vitro.
resultsAsthmatics with high FENO (≥ 35 ppb; 44% of asthmatics) had higher expression of iNOS (P = 0.04) and ARG2 (P = 0.05) in the airway, indicating FENO is a marker of the high arginine metabolic endotype. High FENO asthmatics had the lowest FEV1% (P < 0.001), FEV1/FVC (P = 0.0002) and PC20 (P < 0.001) as compared to low FENO asthmatics or healthy controls. Low FENO asthmatics had near normal iNOS and ARG2 expression (both P > 0.05), and significantly higher PC20 (P < 0.001) as compared to high FENO asthmatics. In vitro studies to evaluate metabolic effects showed that iNOS overexpression and iNOS+ARG2 co-expression in a human bronchial epithelial cell line led to greater reliance on glycolysis with higher rate of pyruvate going to lactate.
conclusionsThe high FENO phenotype represents a large portion of the asthma population, and is typified by greater arginine metabolism and more severe and reactive asthma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.