26 September 2025: Review Articles
Association of Childhood Asthma with the Concept of Exposomics: A Short Review
Martyna Pajewska-Szmyt DOI: 10.12659/MSM.949589
Med Sci Monit 2025; 31:e949589
Abstract
ABSTRACT: Chronic diseases such as asthma, which affect many children, require ongoing monitoring to identify agents that worsen morbidity and cause molecular changes. Asthma is a health condition with genetic and environmental influences. While the molecular mechanisms are still under investigation, the environmental component remains a pivotal part of understanding and managing the disease. The environment largely influences the development of asthma. Therefore, to obtain essential data regarding the effect of environmental exposure, it is vital to use omics science, such as exposomics. Accordingly, the purpose of this review was to collect the most essential information on asthma, with emphasis on early childhood asthma, and to provide an introduction to the role of environmental exposure in relation to asthma, with a background of exposomics. The exposome has recently become a vital interdisciplinary concept, focusing on identifying how environmental agents influence health and disease throughout a person’s life. Consequently, exposomics is the study of the exposome, encompassing measurements of environmental exposure and the associated biological reactions. In addition, attention has been focused on examples of potential environmental pollutants to which children may be exposed in their immediate surroundings, including phthalates, polycyclic aromatic hydrocarbons, per- and polyfluoroalkyl substances, and secondhand smoke. Finally, this review highlights the role of exposomics studies in pediatric asthma in 3 areas: clinical, analytical, and environmental. In summary, in this article, we aim to review the potential effects of the exposome, or multiple environmental factors, on childhood asthma.
Keywords: Asthma, biomarkers, Environmental Exposure, Environmental Pollutants, Humans, Child, Exposome
Introduction
The detailed molecular mechanisms of asthma are still being investigated by researchers [1,2]. Unfortunately, asthma affects millions of people worldwide [1,3,4]. This complex and heterogeneous disease can affect various age groups, including school-age children and newborns [5,6]. Accurate diagnosis and implementation of treatments are crucial in determining how asthma will affect a person’s quality of life [7]. It is also estimated that about 80% of symptoms begin before a child reaches 6 years of age [8,9]. The complexity of asthma is significant, as its symptoms can overlap with those of other respiratory conditions [10]. Meanwhile, diagnosis in children under the age of 5 years is challenging owing to the difficulty of conducting basic examinations, such as spirometry, which, while practical, requires a high level of cooperation from the patient. In addition, accurately identifying the type of asthma is essential in diagnosis, as it directly affects the selection of the type and form of treatment [11,12]. Increasingly more attention has been given to the influence of the environment, mainly organic pollutants, on the progression of airway problems [13]. Additionally, there is a growing public awareness that environmental risk is not limited to the “smoke” that comes from manufacturing plants and other industrial activities, but also includes everyday human-made items, such as plastic bottles, toys, and boxes [14,15]. This raises the question of which biological mechanisms are triggered by exposure to persistent organic pollutants, including endocrine-disrupting compounds [16]. The answer can be provided by the exposome [17,18]. The exposome has been recently widely recognized as an interdisciplinary concept, whose main purpose is to identify how various environmental agents influence both the health and disease states throughout an individual’s lifespan. Additionally, exposomics – the study of the exposome – encompasses measurements of environmental exposure and the corresponding biological responses [17–19]. In omics, the focus of research is aimed also at the recognition of changes in the metabolism of compounds that are in biological samples at trace levels, which is now possible because of advanced analytical techniques, such as mass spectrometry, nuclear magnetic resonance, and coupled techniques [20–22]. Therefore, the purpose of this review was to collect the most relevant information on the challenges of asthma etiology and diagnosis, with emphasis on early childhood asthma, and to introduce the subject of environmental exposure and its connection to asthma in the context of omics science, such as exposomics. This article aims to review the effects of the exposome, or multiple environmental factors, on childhood asthma, as well as provide an example of biological samples that can be used for omics analysis.
General Review of Asthma, a Non-Communicable Disease
PEDIATRIC ASTHMA:
Early childhood asthma deserves special attention, as it is suspected to not be a singular disorder but one characterized by highly variable manifestations, especially in children, who are continuously developing and undergoing dynamic changes over a relatively short period. Additionally, diagnosing pediatric asthma is challenging because symptoms such as coughing, wheezing, and shortness of breath are also common in other respiratory infections [8,10] and chronic diseases. Furthermore, children require particular focus because of the substantial differences between children and adults with asthma in regards to disease development, progression, and treatment, which are largely driven by age-related factors [23].
ASTHMA CLASSIFICATION:
Asthma can be classified in terms of clinical phenotypes and inflammatory or molecular endotypes [23,25]. The clinical phenotype classification is connected with demographic aspects, asthma symptoms, and other physiological characteristics of a particular group. The endotype classification includes the biological response of an organism, in which inflammatory endotypes can be described with, for instance, cytokine levels or other inflammatory markers, such as fractional exhaled nitric oxide (FeNO) [6,23,27]. FeNO testing is a useful test even in children, including those as young as 4 to 5 years old. However, cooperation from the child while the examination is performed is required. Clinical asthma can be divided into 2 main phenotypes, allergic asthma and non-allergic asthma [28]. According to Raedler et al [27], children with allergic asthma have increased levels of Treg cells, compared with the control group. In children with non-allergic asthma, higher levels of interleukin (IL) such as IL-1β and IL-17, along with insufficient suppression of IL-5, IL-13, and interferon γ, have been observed. However, there is now a more intentional approach to using endotype classification in proposing the direct therapies of these diseases [29]. In this context, special emphasis can be placed on the Th2-high endotype, characterized by the occurrence of eosinophilic airway inflammation, and the Th2-low endotype, which involves neutrophilic or paucigranulocytic airway inflammation [29,30]. Whereas this classification is the most widely used, other classification based on T-helper cells, such as Th17 and Th1, have also been proposed [31,32].
OMICS SCIENCES IN ASTHMA STUDIES AND EXAMPLES OF BIOLOGICAL MATRICES USED FOR STUDIES:
Modern technologies such as mass spectrometry and chromatography aid in diagnosing and classifying asthma [33]. To meet the challenges of diagnosing disorders, including asthma, omics sciences can provide molecular-level information that distinguishes metabolome profiles between disease and control groups [11,34,35]. In addition, it is essential to include all bioinformatics tools and available databases that enable the analysis of raw data by identifying statistically significant differences between the investigated samples. Therefore, the combination of mass spectrometry, omics technologies, and bioinformatics provides a powerful and robust framework to support diagnosis based on clinical features and diagnostic laboratory parameters [36], resulting in the more precise recognition of asthma and selection of personalized medical treatments [31]. Several omics sciences are used to explore the challenges of asthma, mainly transcriptomics [37,38], epigenomics [39,40], proteomics [41,42], and metabolomics [1,43,44]. Metabolomics is described as a snapshot of the organism’s physiological condition and includes low-molecular-weight compounds below 1500 Da [45]. In contrast to the vast number of genes and proteins in the body, the number of metabolites is comparatively smaller. However, the magnitude of external factors, including environmental pollution, and internal factors, such as inflammatory conditions, can significantly and variably affect metabolite levels, which may be considered the body’s response to these influences. Frequently, such responses can also be specific to particular physiological states, including pathological conditions [20]. Another pivotal role in asthma studies has started to be filled by lipidomics [46,47], in which the correlation between asthma inflammatory conditions is correlated with lipid composition. Researchers have focused on the sphingolipid class [48] as well as glycerophospholipids [49]. Furthermore, special attention has been directed toward prostaglandins and eicosanoids – mediator lipids that can play crucial roles in asthma and are considered crucial biomarkers [50–52]. The diversity of omics sciences, along with the availability of unique analytical techniques, has oriented research in the direction of simultaneously conducting multi-dimensional studies, using more than one omics approach. Subsequently, in asthma research, the term “multi-omics” can be encountered as a reference to the integration of different omics sciences [36,53]. In addition, in this kind of research, it is possible to use different biosamples for studies. Along with serum [44,54] and urine [50,55], a portfolio of potential matrices includes exhaled breath condensate (EBC) [52,56], saliva [57], and sputum [58]. The wide spectrum of biosample collection options allows the identification of various compounds that can be key in a particular disease state. This approach also considers the differing absorption and metabolism pathways of these compounds within the body. Each matrix has advantages and disadvantages related to technical factors such as sampling methods, cost, and whether the collection approach is invasive or noninvasive [51,59–62] (Figure 1).
Concept of Exposomics and Its Role in Asthma Research
ENVIRONMENTAL POLLUTION AND EXPOSOME CONCEPT:
Therefore, omics science can describe nongenetic factors that affect pediatric asthma. However, this remains an extremely challenging characterization task due to the presence of more than 350 000 chemical contaminants in our environment [69], with this number unfortunately continuing to rise. Although motorization, industry, and other developments have significantly improved daily life and introduced countless products, the cost of global progress includes the release of harmful substances into the environment, which are subsequently absorbed by living organisms. Consequently, these compounds can be considered as specific external exposomes affecting a biological response from the immune system [18]. As shown in Figure 2, the factors involved in exposomic research are numerous; in fact, there are countless possible single and synergistic exposures of multiple factors. Nevertheless, it is necessary to start somewhere, and studies on the correlation of chemical factors in biological samples of children with a diagnosis of asthma are well justified. Exposome experiments can include a “top-down” approach, in which the research is focused on the identification of exogenous compounds as well as metabolomic profiles. Meanwhile, the “bottom-up” approach concentrates on investigating external environmental exposure, for example, from the immediate surroundings. The outcome may be the formulation of a hypothesis on the potential effects on living organisms [70,71]. As an integrative approach, recent literature has proposed the third way, a “meet-in-the-middle” method. This third method retrospectively correlates intermediate biomarkers with data on external exposures, aiming to link disease progression with the physiological changes it induces [15,64,70,71,72,73]. Implementing exposomics into early-age asthma research is reasonable, as the spectrum of environmental factors increasing asthma risk is significant and includes infection, air pollution, allergens, microplastics, and exposure to secondhand smoke [36,74,75]. In addition, it is worth noting the impact of everyday activities – such as dishwashing – on the development of asthma and other allergic diseases. This issue was explored by Hesselmar et al [76], who reported that using a dishwasher is associated with a higher incidence of these conditions, compared with washing dishes by hand. One proposed explanation is that handwashing may expose individuals to a broader microbiome, thereby providing greater immune system stimulation. In contrast, dishwashers reduce microbial exposure, potentially leading to lower immune tolerance and increased susceptibility to allergic diseases in children [76]. The world is overloaded with compounds that can lead to potential respiratory disorders. However, much like human biology, the nature of the environment is dynamically and constantly changing, making research in this area highly heterogeneous [77]. Nevertheless, continued investigation in this broad field is essential to address numerous unanswered questions related to the progression and management of asthma, as well as its analytical and environmental dimensions.
IMPORTANCE OF EXPOSOMIC RESEARCH IN CHILDHOOD ASTHMA:
It should be noted that incorporating exposomic research into early childhood asthma can enhance understanding of how environmental factors affect the respiratory system and raise public awareness about the potential harm of substances present in our immediate surroundings (Figure 3). The risk of adverse effects from exposure is particularly high in young children, as their inhaled air volume per body weight is greater than that of adults [78]. Additionally, the immaturity of detoxification enzyme systems, which are essential for metabolizing and eliminating xenobiotics, leads to an increased exposure time of these harmful compounds in children’s bodies [79].
We analyzed the research on asthma combined with exposomics in the Scopus database (accessed on December 22, 2024) and found that this area is still developing, with roughly 150 scientific publications in less than 15 years. These can be identified by keywords such as “exposome” and “asthma” (Figure 4A). The number of publications for “childhood asthma” and “exposome” search was even lower, with approximately 20 scientific papers (Figure 4B). Notable, the appearance of relevant references began appearing in 2016, and the trend started to show a marked increase beginning around 2021. Therefore, we can see there have been several attempts in the literature to correlate certain contaminants with the occurrence of childhood asthma, as shown in Table 1.
There is no doubt that the compounds listed in Table 1 negatively affect the immune system and can serve as biomarkers of exposure, either as parent compounds or their metabolites. However, the table includes only a few well-known examples. Moreover, the effects of these compounds should be evaluated not only individually, but also in combination, as these exogenous substances can exert synergistic effects. Activation of the aryl hydrocarbon receptor by persistent organic pollutants is already a well-documented mechanism and has been correlated with asthma [13,102,103]. Exposure to such pollutants is one cause of immune system weakening, and as such, creates favorable conditions for disease development.
CHALLENGES OF EXPOSOME STUDIES IN PEDIATRIC ASTHMA:
The complexity of exposomics research arises not only from the wide range of biological matrices and the multitude of compounds to be investigated, but also from the fact that potential analytes can exist at extremely low concentrations and can give rise to a variety of metabolites. Additionally, environmental pollution can be harmful even at low concentrations due to long-term exposure. For example, regulations for children’s toys limit the content of phthalates to not exceed 0.1% by weight [104,105]. In the case of parabens, the content of the paraben mixture in the product cannot exceed 0.8% [106]. Again, it should be highlighted that environmental pollutions, specifically external, are only “small” pieces of the exposome [18]. The factors are widespread, and in fact, a human being is exposed to them to a greater or lesser degree because they are surrounded by allergens, such as plants, animals, and chemicals, and contact with different surfaces, such as microbes exposition, radiation, nutrition, and even medical treatment, which strongly influence the exposomic profile [18,36]. Consequently, exposure to even the smallest factors can disturb the omics profile [18,36]. In addition, the approach and factors in the exposomics domain should be considered on an individual level, with an example being a different effect of endocrine-disrupting compounds on males and females due to sex-specific biological responses [107]. This demonstrates the complexity of exposomics, including a proposal to study asthma using the exposome approach.
Future Directions
Analytical tools, primarily mass spectrometry, address this challenge and create the possibility of exploring previously unknown clinical relationships between diseases and environmental factors. Furthermore, integrating omics with environmental issues requires an interdisciplinary approach with specialists from various fields, including clinical medicine, chemistry, biology, and bioinformatics. Additionally, the key analytical challenge is selecting a suitable matrix – a biological sample for analysis that most accurately represents a child’s exposure to a particular agent while having a collection that is as noninvasive as possible. The extraction method is equally valid, as it substantially affects the quality and reliability of analyte determination. Therefore, analytical efforts should focus particularly on developing new sample preparation methods (incorporating the principles of green chemistry), with special attention to analytes present at trace levels, which can be suppressed by compounds at higher concentrations in biological samples. In addition, it is worth exploring the network of connections between the compounds being examined, to determine, for instance, how a change in one affects the content of another.
Furthermore, studies should be integrated with information collected through dedicated personal questionnaires that include current and retrospective lifestyle data, as well as other essential information necessary to describe potential external and internal exposomic domains [18,108]. Accordingly, there is a need for specialists in this field to develop research questionnaires that provide diverse information relevant to exposomic assessment and support studies conducted by scientists. Additionally, exposomics research should serve as a source of knowledge for the public regarding the potential negative effects of environmental pollution on the organism, as these negative aspects are often marginalized. In summary, exposomics research offers an opportunity for multidisciplinary investigation, and such efforts should lead to balanced progress in clinical, analytical, and environmental fields, including research on early childhood asthma.
Conclusions
Despite the scientific progress made in understanding the relationship between asthma and environmental exposures, questions remain. Therefore, exposomics research can provide essential information by linking exposure sources, such as environmental pollution and chemicals, with metabolomic changes characteristic of asthma. This is a chance to provide a broader context of this health condition, in particular, early-onset asthma. Last, but not least, it is also an opportunity to alert the population to the “unseen” problem of environmental pollutants and their impact on health, which will also provide biomonitoring information.
Figures
Figure 1. Examples of biological samples (exhaled breath condensate; plasma/serum; urine; hair, induced sputum, saliva) for asthma studies in the “Omics” area [51,59–62] with pros and cons. Created in https://BioRender.com.
Figure 2. Exposomics area. Potential source of biomarkers of exposure, which can negatively affect the child, and example of biomarkers of effect as a metabolomic consequence of the response of the organism. Created in https://BioRender.com.
Figure 3. The possible output of application of exposomics in pediatric asthma research in clinical, analytical, and environmental areas.
Figure 4. Number of published papers regarding asthma and exposome. Source of data – Scopus database (https://www.scopus.com/), accessed on December 22, 2024; Figure created in Excel. References
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Figures
Figure 1. Examples of biological samples (exhaled breath condensate; plasma/serum; urine; hair, induced sputum, saliva) for asthma studies in the “Omics” area [51,59–62] with pros and cons. Created in https://BioRender.com.
Figure 2. Exposomics area. Potential source of biomarkers of exposure, which can negatively affect the child, and example of biomarkers of effect as a metabolomic consequence of the response of the organism. Created in https://BioRender.com.
Figure 3. The possible output of application of exposomics in pediatric asthma research in clinical, analytical, and environmental areas.
Figure 4. Number of published papers regarding asthma and exposome. Source of data – Scopus database (https://www.scopus.com/), accessed on December 22, 2024; Figure created in Excel. In Press
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