The role of macroelements in the pathogenesis of bronchial asthma in children

Introduction

According to the numerous epidemiological studies conducted in European countries (International Study of Asthma and Allergy in Childhood, ISAAC), there is a progressive increase in allergic diseases, in particular, bronchial asthma (BA), which is now considered a global challenge and continues to remain the focus of specialists in various fields [1][2][3]. Current statistics show that respiratory allergies account for almost 700 million cases worldwide, with about 330 million cases of BA. The suggestion is that by 2025 this index could reach as much as 400 million [4]. The BA formation mechanism is complex and multifaceted. Until today, the relationship between the development of certain multifactorial diseases with a deficiency, excess, or imbalance of macro- and microelements in the body has been proven [5][6][7][8]. The influence of bio elements on the pathogenetic BA formation mechanism is also under-researched.

The goal of the research was to study the role of macronutrients in BA pathogenesis in children.

Material and methods

 The unselected one-stage examination of 131 patients with BA of varying severity was carried out. The diagnosis was determined by the "Bronchial Asthma in Children. Treatment strategy and prevention" National Program [9]. The control group consisted of 31 children of the respective gender and age groups 1 and 2A. The average age of the children was 11.83 ± 3.38 years.

The patient entry criterion for the study: established BA, age from 3 to 18 years; signed informed consent from parents (for children under 14) and informed consent from children over 14 years old. Withdrawal criteria: residence in the Rostov Region for less than 1 year; the presence of concomitant somatic pathology; acute infectious diseases.

All children understudy in the cohort were given a comprehensive clinical-laboratory examination, pictometry, pulse oximetry, and spirometry. The study of mineral homeostasis in blood serum was carried out by X-ray fluorescence analysis.

Statistical analysis of the obtained data was carried out using the STATISTICA 10 program, Microsoft Office Excel 10, calculations were performed in the R program (version 3.2, R Foundation for Statistical Computing, Vienna, Austria).

Results

Based on the data obtained, it was found that the overwhelming majority of the examined patients had a BA mild course (65.6%), the moderate course in 20.6% of those examined, and the severe one in 13.7% of cases.

The blood serum analysis revealed that there were significant differences between the macronutrients in children with BA and those in the control group (Table 1).

Table 1

Moreover, it is important to note that the content of these macronutrients in patients with varying severity of the disease, on the contrary, did not have significant differences (Table 2).

Table 2

The data obtained indicate an increase in potassium, phosphorus, and sulfur in children with BA compared with the control group. While calcium, magnesium, and chlorine, on the contrary, are lower in the group of patients (p < 0.0001). This is important in terms of BA pathogenesis since a decrease in magnesium can lead to damage of the bronchi contractility, because it is magnesium that activates adenylate cyclase, and it, for its part, catalyzes the cyclic adenosine monophosphate (cAMP) formation and prevents mast cell degranulation, thereby providing relaxation of bronchial smooth muscles.

The decrease in calcium may be due to the depletion of its pool during the intense contraction of bronchial smooth muscles during the period of acute exacerbation, and it also plays a role in maintaining chronic inflammation. It is exactly calcium that can cause the release of mast cell mediators, thereby promoting an increase in mucous gland secretion and the movement of pro-inflammatory cells into the respiratory tract walls.

Particular attention should be paid to phosphorus in blood serum: BA patients have a significant increase in it (2.44 [ 1.97; 3.2] mmol/L) vs the control group (0.63 [ 0.49; 0.9] mmol/L) [p < 0.0001]. Bearing in mind that phosphorus is the main tissue-forming macronutrient that is part of the phospholipids of cell membranes, including the respiratory epithelium, it can be assumed that an increase in this agent in blood serum of BA patients may indicate a chronic inflammatory process in the bronchopulmonary system.

Potassium and chlorine are equally important macronutrients regulating water and electrolyte balance. In addition, they are involved in the synthesis of acetylcholine neurotransmitter, which plays a significant role in the progression of bronchoconstriction, sputum hyperproduction, and edema of the bronchial mucosa [10].

Also, in patients with clinical manifestations of BA, an increase in sulfur in blood serum (4.1 [ 0.94; 4.89] mmol/L) was recorded, compared with the control group (0.49 [ 0.11; 0.63] mmol/L) [p < 0.0001]. The change in this agent concentration is possibly due to the intense processes of oxidative damage to the respiratory tract proteins and glycoproteins that occur during acute exacerbation, since it is sulfur that forms flexible disulfide bonds within proteins, which provide the flexibility and mobility of tissues, and are also included in the structure of a huge amount of receptors and enzymes [11].

Discussion

Despite the special attention focused on the BA etiopathogenesis study, the problem of mineral homeostasis damage in patients with this pathology is poorly understood, and studies focused on this item are often fragmentary without a comprehensive assessment of the identified damages [12][13]. At the same time, the data obtained in this study are consistent with the results obtained by other scientists. Thus, it was proved that Ca²⁺ ions were involved in BA pathogenesis [14]. Moreover, researchers have already formulated the so-called "calcium" theory of the progression of bronchial hyperreactivity syndrome [15][16]. According to few data, Mg deficiency is associated with increased tracheobronchial hyperreactivity, pulmonary vascular resistance, and ventricular arrhythmia [17][18]. In addition, it was found that chlorine (Cl) had a significant toxic effect on the bronchial epithelium, alveoli, and capillary endothelium since it contributed to the inactivation of antioxidant defense system enzymes [19]. In this regard, free radical processes are enhanced, which lead to degeneration, necrosis of the respiratory tract epithelium, and, as a consequence, fibrotization and bronchoconstriction [18][20]. All this indicates the demand to continue research in this prospect and search for biological markers of severe BA.

Conclusion

It was found that BA patients had a significant increase in potassium, phosphorus, and sulfur, as well as a decrease in calcium, magnesium, and chlorine in blood serum vs patients in the control group. The data obtained on changes in macroelement homeostasis indicate the important role of diselementosis in BA pathogenesis. A change in the concentration of these agents is a significant factor contributing to the chronic inflammation progression in the bronchi and requiring therapy correction in children.