Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment

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 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.

Metabolomics, Microbiota, and In Vivo and In Vitro Biomarkers in Type 2 Severe Asthma: A Perspective Review

“…Recently, -omics sciences are also applied in OSA patients. The first proteomic approach in OSA dates back to 2018 with the study by Zhang [55], which highlighted how intermittent hypoxemia is associated with the increase in 4 proteins (CRP, haptoglobin, fibronectin, platelet factor 4) released into the extracellular fluid from part of microvesicles of cells subjected to hypoxic insult. Since then, proteomics and metabolomics studies in OSA have intensified, highlighting several molecules that may represent biomarkers of OSA.…”

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications

“…The reproducibility of metabolomics signatures in asthma may also be checked by comparing results between children and adult studies, since finding similar results will strengthen the possible relevance of detected changes. In fact, several studies in children and in adults have coincided in the main metabolites, at least regarding discrimination between asthma and a healthy state [ 32 , 64 , 88 , 92 , 94 ]. However, comparative studies regarding the capacity to discriminate between asthma inflammatory and/or clinical phenotypes are necessary, although the previously mentioned study by Abdel-Aziz [ 113 ], which showed the capacity of eNose metabolomics in exhaled breath to predict an atopic asthma phenotype in adults and children, is a good example of reproducibility.…”

“…Metabolomics, applied to asthma in children in several studies, has been shown to be able to predict future wheezing and exacerbations, as well as to identify different metabolites in different age groups with the same clinical profile. Thus, with the help of metabolomics, it is possible to predict an outcome for asthmatic children and eventually prevent an unfavourable exacerbation scenario [ 64 , 136 , 137 ]. However, there are comparatively fewer studies in adult asthma that have addressed this issue, in a longitudinal, cohort study.…”

“…The temporal stability and eventual prognostic capacity of metabolic signatures will also be briefly analysed, as well as other aspects that may influence such signatures. Results from studies in children will not be specifically mentioned since there have been two recent reviews focusing on this subpopulation and asthma [ 64 ] or atopic diseases, in general [ 65 ]. Since this is a narrative review, and not a systematic review, this document does not aim to be an exhaustive, comprehensive analysis but rather a conceptual approach to the issue of metabolomics signatures and asthma phenotypes.…”

Metabolomics in the Identification of Biomarkers of Asthma

“…Asthma in children remains a significant public health challenge affecting 5-20% of children in Europe, associated with increased morbidity and societal healthcare costs. 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 [7].…”