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11IMMUNE STATUS IN CHILDREN WITH RECURRENT BRONCHITIS ON THE BACKGROUND OF LYMPHATIC DIATHESIS Sharipova O.A.1, Bahronov Sh.S.2, Ibragimov S.T.3
'Sharipova Oliya Askarovna - Doctor of Medical Sciences, Associate Professor, 2Bahronov Sherzod Samievich - PhD, 3Ibragimov Sardor Tolib ugli - student, DEPARTMENT OF PEDIATRICS №3 AND MEDICAL GENETICS, FACULTY OF PEDIATRICS, SAMARKAND STATE MEDICAL UNIVERSITY, SAMARKAND, REPUBLIC OF UZBEKISTAN
Abstract: lymphatic diathesis in children accompanied by thymomegaly is characterized by a decrease in the adaptive capacity of the body, and also contributes to the development of diseases. Purpose of the study: To study the state of the immunological status in children with recurrent bronchitis against the background of lymphatic diathesis. Materials and methods. We observed 119 children with RB aged 2 to 7 years. The average age of the examined patients was 4.1±0.82 years. The diagnosis of RB was established on the basis of clinical and radiological criteria confirmed in ICD 10 (J40.0). The diagnosis of LD was made on the basis of clinical, laboratory and X-ray studies. RB was verified on the basis ofpathognomonic, clinical manifestations of the disease - complaints, a thorough history of the life and illness of the child (repeated episodes of acute bronchitis 2-3 times or more during the year against the background of acute respiratory infection) and radiographic data Results. Recurrent bronchitis in children with LHD during an exacerbation is characterized by an aggravation of the immune system insufficiency in these patients, manifested by a sharp T-lymphocytopenia and their subpopulation, indicating a functional deficiency of the thymus, and is also accompanied by a decrease in B-lymphocytes and a significant decrease in immunoglobulins IgM, IgG and a deep deficiency IgA, which in turn has a high inverse correlation with the degree of thymomegaly. Keywords: recurrent bronchitis, lymphatic diathesis, thymomegaly, immunoglobulin.
One of the most common lesions of the lower respiratory tract is bronchitis, including recurrent bronchitis, which ranks second in the structure of morbidity in childhood after acute diseases of the upper respiratory tract with an average increase of 1%o per year [1, 3, 6, 12.].
Recurrent bronchitis in children is of particular concern to local pediatricians, since in modern environmental conditions it is difficult to achieve stable clinical remission [1, 2, 6].
An analysis is being made on the problem of differential search for the causes leading to recurrent bronchitis in children [13].
One of the main reasons for the development of RB in children is an unfavorable premorbid background [13]. Such conditions also include constitutional features, among which lymphatic diathesis (LH) is of no small importance.
Today, everyone knows about the leading role of the immune system in the development and course of bronchopulmonary diseases [8, 14]. The central organ of immunopoiesis in children is the thymus gland. Based on this, pediatricians pay special attention to the increase in the thymus gland [10].
Despite the large number of works on the study of the immune system in RB in children, a detailed study of cellular and humoral immunity in children with recurrent bronchitis against the background of lymphatic diathesis is relevant. Disclosure of these changes and their timely correction with immunomodulatory drugs will help reduce the incidence and improve the prognosis in RB.
Purpose of the study: To study the state of the immunological status in children with recurrent bronchitis against the background of lymphatic diathesis.
Materials and Methods: We observed 119 children with RB aged 2 to 7 years. The average age of the examined patients was 4.1±0.82 years. The diagnosis of RB was established on the basis of clinical and radiological criteria confirmed in ICD 10 (J40.0). The diagnosis of LD was made on the basis of clinical, laboratory and X-ray studies. RB was verified on the basis of pathognomonic, clinical manifestations of the disease - complaints (subfebrile temperature, cough, diffuse dry and various wet rales in the lungs), a thorough history of the life and illness of the child (repeated episodes of acute bronchitis 2-3 times or more during the year against the background of acute respiratory infection) and radiographic data (changes in the lung pattern in the absence of infiltrative and focal shadows in the lungs). All patients were divided into 2 groups: Group I included 62 (52%) patients with RB, of which 35 (56%) were boys and 27 (34%) were girls. Group II included 57 (48%) patients with RB on the background of LD: 42 (74%) boys and 15 (26%) girls. In patients of the second group, during the initial examination, attention was paid to the external signs of LD, the state of the thymus and peripheral lymphoid organs. In 48 (84.2%) patients, pasty habitus was noted, which was usually noted from birth. In 35 (61.4%) patients, the birth weight was large, with excessive weight and length gain during the first year of life. In patients with RB on the background of LD, thymomegaly was found in 45 (79%) patients. The degree of thymomegaly was determined by assessing the size of the thymus gland on a chest x-ray based on the value of the cardio-thymic-thoracic index: the ratio of the width of the thymus to the width of the chest at the level of the domes of the diaphragm.
Thymomegaly I degree (CTTI 0.33-0.36) was detected - in 10 (22.3%) patients II (CTTI 0.37-0.42) - y 18(40%) and III degree (CTTI 0,43 or more) - in 17(37.7%) sick children. At the same time, an increase in the
right lobe of the gland was observed in 12 (26.66%), in the left lobe in 19 (42.22%) and in 14 (31.11%) patients there was a bilateral increase in the thymus gland.
The number of circulating T-lymphocytes was estimated by the method of spontaneous rosette formation according to Jondal et.al., (1972). Determination of T-lymphocytes, T-suppressors, T-helpers and B-rosette-forming lymphocytes (in reaction with mouse erythrocytes) was carried out according to I.V. Ponyakina and K.A. Lebedev (1983). Quantitative determination of the concentration of immunoglobulins of the main classes IgG, IgA, IgM, IgE was carried out using a set of reagents for highly sensitive enzyme immunoglobulin determination in blood serum of «Вектор Бест» (Novosibirsk, Russia), using enzyme-linked immunosorbent assay. The study was conducted at the Institute of Immunology and Human Genomics of the Academy of Sciences of the Republic of Uzbekistan. Laboratory of Immunology of Reproduction
Research results. As a result of the immunological studies, a more pronounced suppression of the T-cell link of immunity was found in RB children on the background of LHD than in the group of RB children without LHD (40.5±1.18% and 48.4±0.96%, respectively) (p< 0.001). The average percentage of leukocytes, lymphocytes was statistically significantly higher with the progression of thymomegaly than in LHD children without thymomegaly and in healthy children. The mean values of T-lymphocytes and their regulatory subpopulations were lower in LHD children with thymomegaly than in LD children without thymomegaly, as well as in healthy children. It should be noted that a direct correlation was found between the degree of thymomegaly and the number of leukocytes, lymphocytes (r=+0.71; r=+0.64), as well as an inverse correlation between the degree of thymomegaly and the number of T-lymphocytes and their subpopulations (r =-0.78; r=-0.68; r=-0.61) table 1.
Table 1. Characteristics of correlations between immunity indices and with the degree of thymomegaly.
Indicators LD without thymomegaly LD with thymomegaly
I degree II-III degree
Leukocytes +0,233 +0,269 +0,71
Lymphocytes +0,222 +0,293 +0,64
CD3+, %. -0,304 -0,419 -0,78
CD3+CD8+ -0,201 -0,365 -0,61
CD3+CD4+ -0,336 -0,48 -0,68
Ig A -0,25 -0,352 - 0,69
The relative content of T-helpers had a clear tendency to decrease in patients of both groups compared with healthy children (p<0.001). A significant decrease in the content of CD4+ was noted in children of group II (29.7±0.92%), in contrast to patients of group I (32.75±1.28%, p<0.01). The content of CD8+ in the blood in patients of both groups was reduced compared with the indicators of children in the control group (p<0.01). At the same time, the greatest decrease in CD8+ was found in patients of group II (20.63±0.51% versus 23.75±0.51% in children of group I, p<0.001). When comparing changes in the links of immunity with the degree of thymomegaly, we found a decrease in the relative number of all types of T-lymphocytes, as well as CD8+, as thymomegaly progressed. As is known [4], CD8+ is a subpopulation marker and is expressed in humans on mature T-lymphocytes. A significant decrease in the amount of CD8+ in children of group II is probably associated with a decrease in mature T-lymphocytes.
A quantitative imbalance of CD4+ and CD8+ cells led to a change in the immunoregulatory index in patients of both groups, in which the immunoregulatory index was 1.45±0.04 ^l and 1.37±0.08 ^l compared to healthy children (p < 0.05).
In patients of group II, in contrast to patients of group I, there was a significant decrease in the CD4+/CD8+ index (p < 0.01).
In general, all the above data give an idea that in patients with RB on the background of LHD the immunoregulatory function of T-lymphocytes is more reduced compared to patients with RB.
When analyzing the content of CD16+, we found a significant increase in this indicator in patients with RB against the background of LD compared with the control (p<0.01), in patients with RB, the content of CD16+ did not statistically significantly differ from similar indicators in the healthy group.
Thus, the most decrease in the relative content of T-lymphocytes in patients of group II with lymphatic diathesis is associated with a weakening of the migration of T-cells from the thymus to the peripheral part of the immune system, i.e., in these children, the processes of differentiation of T-lymphocytes are weakened.
Analyzing the B-cell link of immunity and the humoral link in terms of the content of immunoglobulins, we found a significant decrease in B-lymphocytes in patients of group II, while in patients of group I there was a tendency to increase B-lymphocytes.
To characterize the humoral link of immunity, an analysis of the content of immunoglobulins in the blood serum of the examined children 2 was carried out.
Table 2. Indicators of humoral immunity in the studied children with RB.
№ Indicators Conditionally healthy children n = 39 Recurrent bronchitis Group I n = 62 Recurrent bronchitis on the background of LHD II group n=57
1 Ig A (pg/ml) 1,04±0,05 0,58±0,064*** 0,37±0,048***
2 Ig M (pg/ml) 1,13±0,04 1,83±0,08*** 0,95±0,05***
3 Ig G (pg/ml) 10,77±0,63 11,4±0,41 8,87±0,38*
4 Ig E (pg/ml) 30,6±2,3 42,6±2,4*** 36,8±1,9*
Note: * - differences relative to the data of the healthy group are significant (* - P<0.05, ** - P<0.01, *** - P<0.001).
In sick children in group I, an increase in the level of IgM during the period of exacerbation of the disease compared with healthy children (P<0.05) was found, which indicates the presence of an infectious agent. Whereas, the level of IgM was significantly low in patients of group II and amounted to 0.95 ± 0.05 pg/ml, which, apparently, indicates the failure of B-lymphocytes to adequately respond to the infectious agent in children against the background of LD associated with the immaturity of these cells, and as a result, the inability to produce immunoglobulins.
When comparing the changes in the IgM level with the degree of thymomegaly, we found a more pronounced decrease in the III degree of thymomegaly 0.82±0.065 pg/ml, while in the I degree they corres ponded to the standard values of 1.11±0.06 pg/ml, in the II degree there was downward trend compared to the group of healthy children (1.03±0.07 pg/ml versus 1.13±0.04 pg/ml).
When studying the concentration of IgA in blood serum in patients of group I, there was a significant decrease in the content of IgA compared with the control group, which indicates a decrease in the humoral defense of the body. But a lower content of IgA was found in the II-group of patients. Thus, in patients of group II, the level of IgA was 2.8 times lower than the normative data (P<0.001). Also, we found an inverse correlation (-0.69) between the level of Ig A and the degree of thymomegaly. If in children in group II with grade I thymomegaly, the content of Ig A was
0.54.0.084 pg/ml, then in children with grade II-III thymomegaly it was 0.35±0.06 pg/ml (P<0,05). The study of the content of Ig G in the studied groups of patients revealed that its change in children with RB was not significantly significant, and had only a tendency to increase.
In children in the RB group with LD, there was a significant decrease in the level of IgG, respectively 11.4±0.41 pg/ml and 8.87±0.38 pg/ml (p<0.05). A decrease in the content of serum IgG in children of group II may be associated with both a violation of the process of switching the synthesis of IgG isotypes and a violation of the formation of memory B cells. IgE values were high in patients of both groups (p<0.05). At the same time, in patients of the second group with thymomegaly of II-III degree, the level of IgE turned out to be more elevated compared to healthy children, respectively 44.7±2.3 pg/ml and 30.6±2.3 pg/ml (p<0,05).
Thus, it was found that in the children with RB studied by us, the immune response to the infectious agent was insufficient and was characterized by either the development of excessive-hyperergic or infectious syndrome of secondary immunodeficiency, in which case the allergic syndrome of secondary immunodeficiency develops. Our study showed a combination of these syndromes often in patients with RB on the background of LHD.
The above indicates that in RB in children there is a dysregulation of both the cellular and humoral components of the immune response in general. Conclusion.
Recurrent bronchitis in children with LHD during an exacerbation is characterized by an aggravation of the immune system insufficiency in these patients, manifested by a sharp T-lymphocytopenia and their subpopulation, indicating a functional deficiency of the thymus, and is also accompanied by a decrease in B-lymphocytes and a significant decrease in immunoglobulins IgM, IgG and a deep deficiency IgA, which in turn has a high inverse correlation with the degree of thymomegaly.
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