Metabolomics in the Identification of Biomarkers of Asthma

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 29413

Special Issue Editors


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Guest Editor
Basic Medical Sciences, Universidad San Pablo-CEU, 28003 Madrid, Spain
Interests: immunology; asthma; allergy; inflammation; biomarkers

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Guest Editor
Centro Hospitalar Universitário São João, Porto; Faculdade de Medicina, Universidade do Porto; Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal
Interests: biomarkers; asthma; allergy; epidemiology

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Guest Editor
Biomedical Research Institute of Malaga (IBIMA), Malaga, Spain
Interests: united airways; allergen challenges; asthma phenotypes; allergen immunotherpay; biomarkers

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Guest Editor
Karolinska Institutet, Stockholm, Sweden
Interests: analytial chemistry; mass spectrometry; metabolomics; lipid mediators; respiratory medicine

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Guest Editor
Department of Basic Medical Sciences, Facultad de Medicina, Institute of Applied Molecular Medicine (IMMA), Universidad San Pablo CEU, CEU Universities, 28660 Madrid, Spain
Interests: metabolomics; biomarkers; allergy; asthma; personalized medicine

Special Issue Information

Dear Colleagues,

Asthma is a multifactorial, chronic syndrome that causes reversible airway obstruction and airway epithelial remodelling. Currently, over 330 million individuals in the world have asthma, a number that is expected to continue increasing with climate change. To date, the molecular mechanisms underlying asthma endotypes and phenotypes are still not fully understood. Moreover, there is a lack of biomarkers for use in patient stratification according to disease severity, individual response to therapy (e.g., treatment with biologics), or potential for disease onset. Metabolomics, the comprehensive study of metabolites, has emerged as a potential approach to identify novel biomarkers of disease. The application of metabolomics to multiple matrices (e.g., urine, blood, lung fluid, exhaled breath) may improve our comprehension of asthma as well as assist in identifying new markers of disease, developing novel treatment modalities and controlling this debilitating disease.

Dr. María M. Escribese
Dr. André Moreira
Dr. Ibon Eguiluz-Gracia
Prof. Dr. Craig Wheelock
Dr. Alma Villaseñor
Guest Editors

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Keywords

  • Asthma
  • Allergy
  • Biomarkers
  • Metabolomics
  • Precision medicine

Published Papers (9 papers)

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Editorial

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4 pages, 491 KiB  
Editorial
Metabolomics in the Identification of Biomarkers of Asthma
by Alma Villaseñor, Ibon Eguiluz-Gracia, André Moreira, Craig E. Wheelock and María M Escribese
Metabolites 2021, 11(6), 346; https://doi.org/10.3390/metabo11060346 - 29 May 2021
Cited by 8 | Viewed by 3911
Abstract
Asthma is a major non-communicable disease characterized by recurrent attacks of breathlessness and wheezing [...] Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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Research

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19 pages, 2127 KiB  
Article
Development of a Novel Targeted Metabolomic LC-QqQ-MS Method in Allergic Inflammation
by David Obeso, Nuria Contreras, Mariana Dolores-Hernández, Teresa Carrillo, Coral Barbas, María M. Escribese, Alma Villaseñor and Domingo Barber
Metabolites 2022, 12(7), 592; https://doi.org/10.3390/metabo12070592 - 25 Jun 2022
Cited by 3 | Viewed by 1917
Abstract
The transition from mild to severe allergic phenotypes is still poorly understood and there is an urgent need of incorporating new therapies, accompanied by personalized diagnosis approaches. This work presents the development of a novel targeted metabolomic methodology for the analysis of 36 [...] Read more.
The transition from mild to severe allergic phenotypes is still poorly understood and there is an urgent need of incorporating new therapies, accompanied by personalized diagnosis approaches. This work presents the development of a novel targeted metabolomic methodology for the analysis of 36 metabolites related to allergic inflammation, including mostly sphingolipids, lysophospholipids, amino acids, and those of energy metabolism previously identified in non-targeted studies. The methodology consisted of two complementary chromatography methods, HILIC and reversed-phase. These were developed using liquid chromatography, coupled to triple quadrupole mass spectrometry (LC-QqQ-MS) in dynamic multiple reaction monitoring (dMRM) acquisition mode and were validated using ICH guidelines. Serum samples from two clinical models of allergic asthma patients were used for method application, which were as follows: (1) corticosteroid-controlled (ICS, n = 6) versus uncontrolled (UC, n = 4) patients, and immunotherapy-controlled (IT, n = 23) versus biologicals-controlled (BIO, n = 12) patients. The results showed significant differences mainly in lysophospholipids using univariate analyses in both models. Multivariate analysis for model 1 was able to distinguish both groups, while for model 2, the results showed the correct classification of all BIO samples within their group. Thus, this methodology can be of great importance for further understanding the role of these metabolites in allergic diseases as potential biomarkers for disease severity and for predicting patient treatment response. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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12 pages, 1831 KiB  
Article
Metabolomic Profile at Birth, Bronchiolitis and Recurrent Wheezing: A 3-Year Prospective Study
by Silvia Carraro, Valentina Agnese Ferraro, Michela Maretti, Giuseppe Giordano, Paola Pirillo, Matteo Stocchero, Stefania Zanconato and Eugenio Baraldi
Metabolites 2021, 11(12), 825; https://doi.org/10.3390/metabo11120825 - 30 Nov 2021
Cited by 2 | Viewed by 1457
Abstract
There is growing interest for studying how early-life influences the development of respiratory diseases. Our aim was to apply metabolomic analysis to urine collected at birth, to evaluate whether there is any early metabolic signatures capable to distinguish children who will develop acute [...] Read more.
There is growing interest for studying how early-life influences the development of respiratory diseases. Our aim was to apply metabolomic analysis to urine collected at birth, to evaluate whether there is any early metabolic signatures capable to distinguish children who will develop acute bronchiolitis and/or recurrent wheezing. Urine was collected at birth in healthy term newborns. Children were followed up to the age of 3 years and evaluated for the development of acute bronchiolitis and recurrent wheezing (≥3 episodes). Urine were analyzed through a liquid-chromatography mass-spectrometry based untargeted approach. Metabolomic data were investigated applying univariate and multivariate techniques. 205 children were included: 35 had bronchiolitis, 11 of whom had recurrent wheezing. Moreover, 13 children had recurrent wheezing not preceded by bronchiolitis. Multivariate data analysis didn’t lead to reliable classification models capable to distinguish children with and without bronchiolitis or with recurrent wheezing preceded by bronchiolitis neither by PLS for classification (PLS2C) nor by Random Forest (RF). However, a reliable signature was discovered to distinguish children who later develop recurrent wheezing not preceded by bronchiolitis, from those who do not (MCCoob = 0.45 for PLS2C and MCCoob = 0.48 for RF). In this unselected birth cohort, a well-established untargeted metabolomic approach found no biochemical-metabolic dysregulation at birth associated with the subsequent development of acute bronchiolitis or recurrent wheezing post-bronchiolitis, not supporting the hypothesis of an underlying predisposing background. On the other hand, a metabolic signature was discovered that characterizes children who develop wheezing not preceded by bronchiolitis. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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16 pages, 2553 KiB  
Article
Metabolomics Reveals Process of Allergic Rhinitis Patients with Single- and Double-Species Mite Subcutaneous Immunotherapy
by Peiyan Zheng, Guanyu Yan, Yida Zhang, Huimin Huang, Wenting Luo, Mingshan Xue, Na Li, Jian-Lin Wu and Baoqing Sun
Metabolites 2021, 11(9), 613; https://doi.org/10.3390/metabo11090613 - 09 Sep 2021
Cited by 12 | Viewed by 2307
Abstract
Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic diseases. However, there has not been any research on metabolic reactions in relation to AIT with single or mixed allergens. In this study, patients with allergic rhinitis caused by [...] Read more.
Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic diseases. However, there has not been any research on metabolic reactions in relation to AIT with single or mixed allergens. In this study, patients with allergic rhinitis caused by Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were treated with single-mite (Der p) and double-mite (Der p:Der f = 1:1) subcutaneous immunotherapy (SCIT), respectively. To compare the efficacy and the dynamic changes of inflammation-related single- and double-species mite subcutaneous immunotherapy (SM-SCIT and DM-SCIT), we performed visual analogue scale (VAS) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score and serum metabolomics in allergic rhinitis patients during SCIT. VAS and RQLQ score showed no significant difference in efficacy between the two treatments. A total of 57 metabolites were identified, among which downstream metabolites (5(S)-HETE (Hydroxyeicosatetraenoic acid), 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11-hydro TXB2) in the ω-6-related arachidonic acid and linoleic acid pathway showed significant differences after approximately one year of treatment in SM-SCIT or DM-SCIT, and the changes of the above serum metabolic components were correlated with the magnitude of RQLQ improvement, respectively. Notably, 11(S)-HETE decreased more with SM-SCIT, and thus it could be used as a potential biomarker to distinguish the two treatment schemes. Both SM-SCIT and DM-SCIT have therapeutic effects on patients with allergic rhinitis, but there is no significant difference in efficacy between them. The reduction of inflammation-related metabolites proved the therapeutic effect, and potential biomarkers (arachidonic acid and its downstream metabolites) may distinguish the options of SCIT. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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Review

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15 pages, 292 KiB  
Review
Metabolomics, Microbiota, and In Vivo and In Vitro Biomarkers in Type 2 Severe Asthma: A Perspective Review
by Cristiano Caruso, Stefania Colantuono, Alberto Nicoletti, Stefania Arasi, Davide Firinu, Antonio Gasbarrini, Angelo Coppola and Loreta Di Michele
Metabolites 2021, 11(10), 647; https://doi.org/10.3390/metabo11100647 - 22 Sep 2021
Cited by 6 | Viewed by 2663
Abstract
Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient; thus, it could be a new approach for the management of severe asthma that considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also [...] Read more.
Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient; thus, it could be a new approach for the management of severe asthma that considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. Metabolomics is the systematic study of low molecular weight (bio)chemicals in a given biological system and offers a powerful approach to biomarker discovery and elucidating disease mechanisms. In this point of view, metabolomics could play a key role in targeting precision medicine. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
20 pages, 1386 KiB  
Review
Research Progress of Metabolomics in Asthma
by Chao Wang, Shengyu Jiang, Siyu Zhang, Zhuoer Ouyang, Guoqiang Wang and Fang Wang
Metabolites 2021, 11(9), 567; https://doi.org/10.3390/metabo11090567 - 24 Aug 2021
Cited by 20 | Viewed by 4044
Abstract
Asthma is a highly heterogeneous disease, but the pathogenesis of asthma is still unclear. It is well known that the airway inflammatory immune response is the pathological basis of asthma. Metabolomics is a systems biology method to analyze the difference of low molecular [...] Read more.
Asthma is a highly heterogeneous disease, but the pathogenesis of asthma is still unclear. It is well known that the airway inflammatory immune response is the pathological basis of asthma. Metabolomics is a systems biology method to analyze the difference of low molecular weight metabolites (<1.5 kDa) and explore the relationship between metabolic small molecules and pathophysiological changes of the organisms. The functional interdependence between immune response and metabolic regulation is one of the cores of the body’s steady-state regulation, and its dysfunction will lead to a series of metabolic disorders. The signal transduction effect of specific metabolites may affect the occurrence of the airway inflammatory immune response, which may be closely related to the pathogenesis of asthma. Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of asthma. The review aims to analyze the changes of metabolites in blood/serum/plasma, urine, lung tissue, and exhaled breath condensate (EBC) samples, and further reveals the potential pathogenesis of asthma according to the disordered metabolic pathways. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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30 pages, 2667 KiB  
Review
Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications
by Adalberto Santos, Helena Pité, Cláudia Chaves-Loureiro, Sílvia M. Rocha and Luís Taborda-Barata
Metabolites 2021, 11(8), 534; https://doi.org/10.3390/metabo11080534 - 11 Aug 2021
Cited by 7 | Viewed by 3452
Abstract
Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or [...] Read more.
Bronchial asthma is a chronic disease that affects individuals of all ages. It has a high prevalence and is associated with high morbidity and considerable levels of mortality. However, asthma is not a single disease, and multiple subtypes or phenotypes (clinical, inflammatory or combinations thereof) can be detected, namely in aggregated clusters. Most studies have characterised asthma phenotypes and clusters of phenotypes using mainly clinical and inflammatory parameters. These studies are important because they may have clinical and prognostic implications and may also help to tailor personalised treatment approaches. In addition, various metabolomics studies have helped to further define the metabolic features of asthma, using electronic noses or targeted and untargeted approaches. Besides discriminating between asthma and a healthy state, metabolomics can detect the metabolic signatures associated with some asthma subtypes, namely eosinophilic and non-eosinophilic phenotypes or the obese asthma phenotype, and this may prove very useful in point-of-care application. Furthermore, metabolomics also discriminates between asthma and other “phenotypes” of chronic obstructive airway diseases, such as chronic obstructive pulmonary disease (COPD) or Asthma–COPD Overlap (ACO). However, there are still various aspects that need to be more thoroughly investigated in the context of asthma phenotypes in adequately designed, homogeneous, multicentre studies, using adequate tools and integrating metabolomics into a multiple-level approach. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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29 pages, 461 KiB  
Review
Potential Metabolic Biomarkers in Adult Asthmatics
by Soyoon Sim, Youngwoo Choi and Hae-Sim Park
Metabolites 2021, 11(7), 430; https://doi.org/10.3390/metabo11070430 - 30 Jun 2021
Cited by 14 | Viewed by 3218
Abstract
Asthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. [...] Read more.
Asthma is the most common chronic airway inflammation, with multiple phenotypes caused by complicated interactions of genetic, epigenetic, and environmental factors. To date, various determinants have been suggested for asthma pathogenesis by a new technology termed omics, including genomics, transcriptomics, proteomics, and metabolomics. In particular, the systematic analysis of all metabolites in a biological system, such as carbohydrates, amino acids, and lipids, has helped identify a novel pathway related to complex diseases. These metabolites are involved in the regulation of hypermethylation, response to hypoxia, and immune reactions in the pathogenesis of asthma. Among them, lipid metabolism has been suggested to be related to lung dysfunction in mild-to-moderate asthma. Sphingolipid metabolites are an important mediator contributing to airway inflammation in obese asthma and aspirin-exacerbated respiratory disease. Although how these molecular variants impact the disease has not been completely determined, identification of new causative factors may possibly lead to more-personalized and precise pathway-specific approaches for better diagnosis and treatment of asthma. In this review, perspectives of metabolites related to asthma and clinical implications have been highlighted according to various phenotypes. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
36 pages, 1322 KiB  
Review
Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment
by Maria Michelle Papamichael, Charis Katsardis, Evangelia Sarandi, Spyridoula Georgaki, Eirini-Sofia Frima, Anastasia Varvarigou and Dimitris Tsoukalas
Metabolites 2021, 11(4), 251; https://doi.org/10.3390/metabo11040251 - 18 Apr 2021
Cited by 30 | Viewed by 4725
Abstract
Asthma in children remains a significant public health challenge affecting 5–20% of children in Europe and is associated with increased morbidity and societal healthcare costs. The high variation in asthma incidence among countries may be attributed to differences in genetic susceptibility and environmental [...] Read more.
Asthma in children remains a significant public health challenge affecting 5–20% of children in Europe and is associated with increased morbidity and societal healthcare costs. The high variation in asthma incidence among countries may be attributed to differences in genetic susceptibility and environmental factors. This respiratory disorder is described as a heterogeneous syndrome of multiple clinical manifestations (phenotypes) with varying degrees of severity and airway hyper-responsiveness, which is based on patient symptoms, lung function and response to pharmacotherapy. However, an accurate diagnosis is often difficult due to diversities in clinical presentation. Therefore, identifying early diagnostic biomarkers and improving the monitoring of airway dysfunction and inflammatory through non-invasive methods are key goals in successful pediatric asthma management. Given that asthma is caused by the interaction between genes and environmental factors, an emerging approach, metabolomics—the systematic analysis of small molecules—can provide more insight into asthma pathophysiological mechanisms, enable the identification of early biomarkers and targeted personalized therapies, thus reducing disease burden and societal cost. The purpose of this review is to present evidence on the utility of metabolomics in pediatric asthma through the analysis of intermediate metabolites of biochemical pathways that involve carbohydrates, amino acids, lipids, organic acids and nucleotides and discuss their potential application in clinical practice. Also, current challenges on the integration of metabolomics in pediatric asthma management and needed next steps are critically discussed. Full article
(This article belongs to the Special Issue Metabolomics in the Identification of Biomarkers of Asthma)
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