**1. Introduction**

Modern medicine is constantly developing, and new, minimally invasive methods are sought to facilitate accurate diagnosis and control the course of the disease. Undoubtedly, a breakthrough event was the recognition of microRNA molecules (miRNAs) which are involved in many biological processes in cells. These biomolecules can be found in blood serum, tissues, and exhaled breath condensate (EBC). They were discovered more than 30 years ago, but only recently have they become a special object of interest among scientists [1–3]. By changing their concentration in the blood serum and knowing the target site of action, they may serve as an extremely useful diagnostic and therapeutic tool allowing us to monitor the course of the disease and detect its exacerbations. Based on a large number of studies, it has been shown that they play a key role in the pathogenesis of allergic diseases (including asthma) by affecting the change in gene expression and modulation of inflammatory processes [4]. Thanks to their minimal invasiveness and the ease of obtaining them, miRNAs are becoming an extremely useful tool in the hands of physicians, especially among the pediatric population. The correct diagnosis of early childhood asthma among this group is often a major clinical problem [5]. Spirometry, i.e., a functional test of the respiratory system, is the gold standard for diagnosing asthma but it requires the cooperation of the patient which is only possible when the child is five to six years old. Due to the still small amount of data on the use of miRNAs among the pediatric

**Citation:** Kierbied ´z-Guzik, N.; Soza ´nska, B. The Potential Role of Serum and Exhaled Breath Condensate miRNAs in Diagnosis and Predicting Exacerbations in Pediatric Asthma. *Biomedicines* **2023**, *11*, 763. https://doi.org/10.3390/ biomedicines11030763

Academic Editor: Stanislawa Bazan-Socha

Received: 28 January 2023 Revised: 23 February 2023 Accepted: 27 February 2023 Published: 2 March 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

population, there is a further need for research to assess their clinical utility in a group of young patients at high risk of an adverse course of the disease.

MiRNAs are small, non-coding RNA molecules, which usually consist of 18–25 nucleotides responsible for regulating gene expression at the translation level and affecting messenger RNA (mRNA) [1]. By binding to the 3 -UTR region, mRNAs lead to the inhibition of translation or degradation in this molecule. These biomarkers act by inhibiting the production of relevant proteins; therefore, it is assumed that the pro-inflammatory effects are probably due to indirect mechanisms [3,6,7]. Approximately 50% of the human genome is regulated by these molecules at the translation stage, which is why they have a significant impact on ensuring homeostasis in the body and coordination of the cell cycle, differentiation, apoptosis, and other physiological functions of cells [8]. Through detailed characterization of the miRNA profile in a given disease entity and correlation of this profile with the appropriate genes, a deeper understanding of the pathophysiological processes will be possible [1,4]. These biomolecules are characterized by high stability and tissue specificity, which emphasizes their additional advantages as new diagnostic markers [8]. MiRNAs have also been shown to be a promising target for potential therapeutic intervention [6,7]. We can divide them into intracellular and extracellular molecules. Thanks to the so-called exosomes, they are transported and transferred between different tissues and cells within the body [3]. Extensively conducted studies have shown a difference in the expression of miRNAs between asthmatics and healthy people. In some of them, the detailed molecular mechanism responsible for the biological processes taking place in cells has already been identified, but most of them are still undiscovered [3,6,7].

Asthma is a chronic inflammatory disease of the bronchial tree characterized by recurrent symptoms, such as cough, shortness of breath, wheezing, and chest tightness, that change in intensity over time. It is the most common chronic disease of the lower respiratory tract in children, usually diagnosed before the age of five (one to two years 34%, less than one year 32%). This may suggest over-diagnosis, because children often cough and wheeze with colds and chest infections, but this is not necessarily asthma [9]. In older children, lung function tests can be used to aid the diagnosis [10]. MiRNA in asthma, through indirect mechanisms, is responsible for the severity of inflammation, hyperresponsiveness, and remodeling of the airways, as well as resistance to standard therapy with inhaled steroids [6]. Moreover, allergens, infections, and air pollution may cause intensification and exacerbation of asthma (especially among children), change the concentration of miRNAs in the serum, and modulate the course of the disease process. The following publication, based on a literature review, aims to introduce miRNAs as new diagnostic markers that allow us to monitor the course of the disease, as well as to recognize and predict its exacerbation, with particular emphasis on the pediatric population [5]. This potential role of miRNAs in pediatric asthma we presented in Figure 1.

**Figure 1.** Serum and exhaled breath condensate-isolated miRNA and its potential role in asthma diagnostics and management in the pediatric population.
