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UDC 616.211-002-056.3-053.2:615.83:546.214:612.017 DOI 10.24412/2220-7880-2024-3-13-17
CLINICAL, IMMUNOMODULATORY AND ANTI-RECURRENCE EFFECTS OF OZONE THERAPY IN CHILDREN WITH PERSISTENT ALLERGIC RHINITIS
Illek Ya. Yu., Suetina I. G., Khlebnikova N. V., Tarasova E. Yu., Leushina N. P., Mishchenko I. Yu., VyaznikovaM. L., Ryseva L. L., Rassanova E. A.
Kirov State Medical University, Kirov Russia (610027, Kirov, K. Marx St., 112), e-mail: yanillek@gmail.com
Research objective: evaluation of the effectiveness of ozone therapy in children with a moderate course of persistent allergic rhinitis. Children aged 5-10 years with moderate persistent allergic rhinitis were under observation. Clinical parameters and immunogram were studied in these children during the period of exacerbation of the disease and at the onset of complete clinical remission. The observed patients were divided into two groups depending on the therapy. The first group of patients (47 patients) received complex conventional treatment, the second group of patients (53 patients) received complex conventional treatment in combination with two courses of ozone therapy. In the second group of patients with allergic rhinitis, compared with the first group of patients, there was a faster positive dynamics of clinical indicators, normalization of most parameters of immunological reactivity and a longer clinical remission.
Keywords: allergic rhinitis, clinical parameters, immunological reactivity, ozone therapy, clinical remission.
КЛИНИЧЕСКИЙ, ИММУНОМОДУЛИРУЮЩИЙ И ПРОТИВОРЕЦИДИВНЫЙ ЭФФЕКТЫ ОЗОНОТЕРАПИИ У ДЕТЕЙ С ПЕРСИСТИРУЮЩИМ АЛЛЕРГИЧЕСКИМ РИНИТОМ
ИллекЯ.Ю., СуетинаИ.Г., ХлебниковаН. В., ТарасоваЕ. Ю., ЛеушинаН. П., Мищенко И. Ю., ВязниковаМ. Л., Рысева Л. Л., Рассанова Е. А.
ФГБОУ ВО «Кировский государственный медицинский университет» Минздрава России, Киров, Россия (610027, г. Киров, ул. К. Маркса, 112), e-mail: yanillek@gmail.com
Цель исследования: оценка эффективности озонотерапии у детей со среднетяжелым течением персистиру-ющего аллергического ринита. Под наблюдением находились дети в возрасте 5-10 лет со среднетяжелым персистирующим аллергическим ринитом, у которых в период обострения заболевания и при наступлении полной клинической ремиссии исследовали клинические показатели и иммунограмму. Наблюдаемые пациенты были подразделены на две группы в зависимости от проводимой терапии. Первая группа больных (47 пациентов) получала комплексное общепринятое лечение, вторая группа больных (53 пациента) - комплексное общепринятое лечение в сочетании с двумя курсами озонотерапии. Во второй группе больных аллергическим ринитом, по сравнению с первой группой пациентов, констатировались более быстрая положительная динамика клинических показателей, нормализация большинства параметров иммунологической реактивности и более продолжительная клиническая ремиссия.
Вятский медицинский вестник, № 3 (83), 2024
Ключевые слова: аллергический ринит, клинические показатели, иммунологическая реактивность, озонотерапия, клиническая ремиссия.
Introduction
Allergic rhinitis is the most common allergopathy [1-3]. In children, it often develops against the background of atopic dermatitis. At the same time, allergic rhinitis can occur in children as an independent disease. Its manifestations usually begin to appear at the age of 4-6 years. Hereditary predisposition, atopy and hyperreactivity of the nasal mucosa play an important role in the development of allergic rhinitis. The triggering factors of allergic rhinitis are household, epidermal, pollen, fungal, viral and bacterial allergens [1, 2, 4-6]. In accordance with the classification of Bousquet J. (2001), recommended by WHO experts (2003) for use in clinical practice, there are [7, 8] intermittent (seasonal, acute, accidental) and persistent (year-round, chronic, long-term) allergic rhinitis.
Modern conventional treatment of children with allergic rhinitis is based on the elimination of allergens, the use of decongestants, antihistamines, cromones and intranasal glucocorticosteroids [6, 1, 4, 7, 9, 10]. However, such treatment is often not effective enough and does not ensure the onset of prolonged clinical remission in patients with persistent allergic rhinitis.
Currently, ozone therapy is successfully used in the complex treatment of a number of acute and chronic diseases in adults and children of different ages, which has anti-inflammatory, analgesic, detoxification, bactericidal, viricidal, fungicidal, antioxidant and immunomodulatory effects, activates metabolism [11, 12]. However, there is no data in the literature on the use of ozone therapy in a complex of therapeutic measures in children with persistent allergic rhinitis, which served as the basis for this study.
The purpose of the study. To determine the clinical, immunomodulatory and anti-relapse effects of ozone therapy in moderate persistent allergic rhinitis in children.
Material and methods
100 children (57 boys and 43 girls) aged 5-10 years with a moderate course of persistent allergic rhinitis (PAR) were under observation. The patients were divided into two groups depending on the therapy. The first group of patients (47 patients) received complex conventional therapy. The second group of patients (53 patients) received complex treatment in combination with ozone therapy.
Parents of patients of both groups were given advice on creating hypoallergenic living conditions. Patients were recommended an individual hypoallergenic diet. Patients of the first group were prescribed Cetirizine dihydrochloride "Zirtek" (10 drops orally, 1 time a day, for two weeks), Oxymetazoline hydrochloride "Nazivin" in the spray form (0.05% one inhalation, 2 times a day, for a week), Fluticasone furoate "Avamis" in the spray form (injection of 1 dose (27.5 mcg) into each nasal passage, 1 time per day for two weeks). The patients of the second group were prescribed generally the same treatment, but in combination with ozone therapy. For ozone therapy, the ultrasonic low-frequency otorhinolaryngological device "Tonsillor-MM" (developed by SPE "Metromed", Omsk) was used. At the same time, a waveguide instrument "VI 16" was inserted into the area of the vestibule of the nose through a guide fluoroplastic sleeve and, after switching on the control unit, low-frequency ultrasonic sanitation of the mucous membrane of the nose was performed by spraying with a jet-aerosol torch (5 sprays of 10 seconds for each half of the nose, daily, for 10 days) with an ozonated 10% oil emulsion [13].
Ozone production was carried out using the synthesizer "A-s-G0KSf-5-050Z0N" (certificate of conformity No. ROSSRU.001.11IM25. Complies with the requirements of normative documents GOST R 50444-92 (Pp-3.4), GOST R 0267.0267.0-92, GOST R 50267.0.2005), in which ozone is obtained by the action of a quiet electric discharge on oxygen (manufacturer: JSC "Electric Machine Building Plant "LEPSE", Kirov). Olive oil for the preparation of a 10% oil emulsion was ozonized at an ozone concentration of 20 mg/ml at the outlet of the synthesizer, the bubbling time of 100 ml of olive oil was 15 minutes.
The first course of complex conventional therapy and the first course of complex treatment in combination with ozone therapy were performed in patients of the corresponding groups from 1-2 days of follow-up. The second course of complex conventional therapy and the second course of complex treatment in combination with ozone therapy were carried out three months after the start of follow-up. There were no complications or adverse reactions in patients during ozone therapy sessions. Catamnestic observation of patients was carried out during the year.
To assess the state of immunity in the first and second groups of patients with moderate persistent rhinitis, the content of populations and subpopulations of lymphocytes in the blood (CD3-l, CD4-l, CD8-l, HLA-DR+-l, CD16-l, CD20-l) was determined in the first 1-2 days of observation (the period of exacerbation of the disease) and 17-20 days after the start of observation and treatment (the period of clinical remission). The CD4/CD8 immunoregulatory index (IRI) was also calculated, and the content of immunoglobulins (IgG, IgA, IgM, IgE) and circulating immune complexes (CIC) in blood serum was studied. The parameters of the phagocytic activity of neutrophils (PHAN), phagocytic index (PHI) and the nitrosine tetrazolium reduction test in the cytoplasm of neutrophils (NST-test) were analyzed. The control group in these studies consisted of 83 practically healthy children of the same age living in Kirov and the Kirov region of the Russian Federation.
Indirect immunofluorescence reaction (IIR) was used to determine the content of CD3-l, CD4-l, CD8-l, HLA-DR+-l, CD16-l and CD20-lymphocytes in the blood of patients with allergic rhinitis. In this reaction, immunophenotyping was performed using sets of monoclonal antibodies LT3, LT4, LT8, MKA HLA-DR, LT16 and LT20, manufactured by Nizhny Novgorod SPC "Drug" LLC. The research results were expressed in percentages and absolute numbers. The CD4/CD8 immunoregulatory index was the ratio of the percentage of CD4- and CD8- lymphocytes in the blood.
The content of immunoglobulins of classes G, A, M, E in the blood serum of patients with allergic rhinitis was determined by enzyme immunoassay (ELISA) in accordance with the instructions for "Immunoscreen-G, A, M, E ELISA-Best" reagents set (Vector-Best CJSC, Novosibirsk). The results of the study of the content of immunoglobulins G, A, M in blood serum were expressed in g/l, and the results of the study of the content of immunoglobulin E in blood serum were expressed in IU/ml. The content of circulating immune complexes in the blood serum of patients with allergic rhinitis was determined by precipitation in a solution of polyethylene glycol [14]. The results were expressed in units of optical density.
The phagocytic activity of neutrophils in patients with allergic rhinitis was evaluated using latex particles with a size of 1.1 mcm ("Sigma", USA) as a phagocytic
object, according to the method of Potapova S. G. et al. [15]. The results were expressed as a percentage. The phagocytic index was calculated as the average number of latex particles absorbed by one neutrophil. The spontaneous NST- test was evaluated in patients with allergic rhinitis by counting the number of cells forming granules of insoluble diformazane [16]. The results were expressed as a percentage.
The data obtained during the study of clinical and immunological parameters in patients with allergic rhinitis were processed by the method of variation statistics. The digital material was processed on a personal computer in the Microsoft Office Excel Mac 2011 application. The results of special studies in groups of patients with allergic rhinitis were compared with each other and with the results of these studies in practically healthy children.
Results and discussion
The main objectives of therapeutic measures in the observed children with a moderate course of persistent allergic rhinitis were to eliminate exacerbation of inflammation of the nasal mucosa and other manifestations of the disease, reduce the body's readiness for an allergic reaction and increase the duration of clinical remission.
Observations have shown that complex conventional therapy and complex treatment in combination with ozone therapy, carried out in the appropriate groups of patients with moderate persistent allergic rhinitis, contributed to improving well-being and appetite, normalizing sleep, reducing and then disappearing hoarseness of voice and spastic cough, normalization of nasal breathing, cessation of itching in the nose and sneezing, cessation of mucous or watery nasal discharge, normalization of the rhinoscopic picture (Table 1).
Table 1
The terms of liquidation of the main clinical symptoms
in the first group of patients with PAR receiving complex conventional therapy, and in the second group of patients with PAR receiving complex treatment in combination with ozone therapy (M±m)
Note: «*» -р<0,001 compared with the indicators in the first group ofpatients with allergic rhinitis who received complex conventional therapy.
At the same time, the elimination of the main clinical symptoms of the disease in the second group of patients with allergic rhinitis who received complex treatment in combination with ozone therapy occurred 0.7-2.9 days earlier (p<0,001) than in the first group of patients with allergic rhinitis who received complex conventional therapy. The onset of complete clinical remission in the first group of patients with allergic rhinitis who received complex conventional therapy was noted 16,8±0,4 days after the start of treatment, and in the second group of patients with allergic rhinitis who received complex treatment in combination with ozone therapy - 13,1±0,5 days after the start of treatment. Thus, in the second group of patients with persistent allergic rhinitis who received complex treatment in combination with ozone therapy, the onset of clinical remission was recorded on average 3.7 days earlier than in the first group of patients with persistent allergic rhinitis who received complex conventional therapy.
The results obtained in the study of the parameters of immunological reactivity in the first group of patients with persistent allergic rhinitis who received complex conventional therapy, and in the second group of patients with persistent allergic rhinitis who received complex treatment in combination with ozone therapy are presented in Tables 2 and 3.
From the material shown in table 2, it follows that in the first and second groups of patients with persistent allergic rhinitis during the period of exacerbation of the disease, there was an increase in the relative and absolute number of CD3- lymphocytes (p<0,001, p<0,001, p<0,001, p<0,001), a decrease in the relative number of CD4-lymphocytes (p<0,001, p<0,001), an increase in the relative and absolute number of CD8-lymphocytes (p<0,001, p<0,001, p<0,001, p<0,001), a decrease in the CD4/CD8 immunoregulatory index (p<0,01, p<0,001), a decrease in the relative number of HLA-DR+-lymphocytes (p<0,001, p<0,01), a decrease in the relative number of CD16-lymphocytes (p<0,001, p<0,001) with an increase in the absolute number of these cells (p<0,001, p<0,001), an increase in the relative and absolute number of CD20-lymphocytes (p<0,05, p<0,05, p<0,001, p<0,001) in the blood. At the same time, there was no statistically significant difference between the relative and absolute number of populations and subpopulations of lymphocytes in the blood in the first and second groups of patients with allergic rhinitis during the exacerbation of the disease.
During the period of clinical remission, ambiguous changes in the content of lymphocytic cells in the blood were recorded in the first and second groups of patients with persistent allergic rhinitis. Thus, in the first group of patients with allergic rhinitis who received complex conventional therapy (tab. 2), during clinical remission, there was an increase in the relative and absolute number of CD3-lymphocytes (p<0,02, p<0,001), a decrease in the relative number of CD4-lymphocytes (p<0,01), an increase in the relative and absolute number of CD8-lymphocytes (p<0,02, p<0,05), a decrease in the relative number of HLA-DR+-lymphocytes (p<0,001), an increase in the relative and absolute number of CD20-lymphocytes (p<0,05, p<0,001) in the blood. In the second group of patients with allergic rhinitis who received complex treatment in combination with ozone therapy (Table 2), during clinical remission, only an increase in the absolute number of CD3-lymphocytes (p<0,001) was recorded and there were no statistically significant changes in the content of other lymphocytic cells in the blood.
Clinical symptoms The terms of liquidation of the main clinical symptoms (days)
The first group of patients PAR (n=47) The second group of patients PAR (n=53)
Normalization of well-being and appetite 6,7±0,2 4,4±0,1*
Normalization of sleep 5,6±0,2 4,0±0,2*
Disappearance of hoarseness of voice and spastic cough 6,9±0,1 5,2±0,2*
Normalization of nasal breathing 6,4±0,3 5,0±0,1*
Disappearance of itching in the nose 5,5±0,2 4,3±0,2*
Stopping sneezing 5,0±0,2 4,3±0,1*
Cessation of mucous or watery discharge from the nose 8,3±0,3 7,0±0,1*
Normalization of the rhinoscopic picture 14,3±0,4 11,4±0,3*
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Table 2
Populations and subpopulations of lymphocytes in the blood of the first group of sick PAR receiving complex conventional therapy,and in the second group of sick PAR receiving complex treatment in combination with ozone
therapy ^±m)
Indicators Healthy children, n=83 The period of exacerbation of the disease The period of clinical remission
1st group of patients PAR, n=47 2nd group of patients PAR, n=53 1st group of patients PAR, n=47 2nd group of patients PAR, n=53
CD3-1, % 64,10±1,25 72,47±1,38* 79,20±1,80* 68,83±1,41* 65,10±1,02
CD3-1, 109/l 1,04±0,07 1,97±0,16* 1,98±0,18* 1,73±0,12* 1,45±0,12*
CD4-1, % 49,80±0,80 41,63±1,87* 41,82±1,90* 43,70±1,94* 48,27±1,05
CD4-1, 109/l 0,73±0,03 0,90±0,10 0,93±0,12 0,81±0,08 0,62±0,06
CD8-1, % 25,50±0,50 31,83±1,70* 32,72±1,65* 28,76±1,30* 25,13±0,68
CD8-1, 109/l 0,36±0,01 0,60±0,05* 0,58±0,04* 0,45±0,04* 0,32±0,03
IRI CD4/CD8 2,10±0,06 1,50±0,18* 1,53±0,16* 1,82±0,24 1,95±0,19
HLA-DR+-1, % 19,50±1,06 13,40±1,69 13,87±1,70* 15,73±1,34* 18,50±1,25
HLA-DR+-1, 109/1 0,33±0,02 0,42±0,02 0,38±0,04 0,39±0,04 0,34±0,05
CD16-1, % 18,20±1,95 12,67±1,18* 12,70±1,09* 17,10±1,81 16,90±1,18
CD16-1, 109/1 0,37±0,05 0,63±0,06* 0,66±0,05* 0,39±0,05 0,37±0,04
CD20-1, % 9,30±0,77 11,73±0,91* 11,57±0,73* 12,10±0,76* 9,73±0,64
CD20-1, 109/1 0,17±0,02 0,34±0,03* 0,28±0,03* 0,33±0,03* 0,22±0,03
Note: «*» - p<0,05—0,001 compared with the indicators in practically healthy children.
Table 3
The content of immunoglobulins and circulating immune complexes in blood serum, phagocytosis indicators in the first group of patients with PAR receiving complex conventional therapy, and in the second group of patients with PAR receiving complex treatment in combination with ozone therapy ^±m)
Indicators Healthy children, n=83 The period of exacerbation of the disease The period of clinical remission
1st group of patients PAR, n=47 2nd group of patients PAR, n=53 1st group of patients PAR, n=47 2nd group of patients PAR, n=53
IgG, g/1 8,90±0,14 11,15±0,38* 11,22±0,40* 10,24±0,20* 9,07±0,15
IgA, g/1 0,86±0,03 1,03±0,14 1,01±0,12 0,99±0,14 1,12±0,24
IgM g/1 1,10±0,04 1,72±0,09* 1,69±0,10* 1,44±0,07* 1,26±0,08
IgE, ME/m1 91,00±26,20 535,80±40,04* 524,80±41,91* 492,30±51,71* 281,50±32,16*
CEC, un.opt.p1. 0,070±0,004 0,067±0,002 0,069±0,003 0,075±0,005 0,070±0,003
FAN, % 66,70±1,11 76,50±1,99* 76,27±2,22* 73,37±1,81* 68,80±2,15
FI 10,80±0,17 8,62±0,97* 8,79±0,93* 9,39±0,50* 10,64±0,14
NST-test, % 17,70±0,69 12,57±1,10* 12,87±0,93* 15,53±0,82* 17,73±0,78
Note: «*» - p<0,05-0,001 compared with the indicators in practically healthy children.
In both groups of patients with persistent allergic rhinitis during the period of exacerbation of the disease (Table 3), shifts in serum immunoglobulin levels were found to be identical in nature, which manifested themselves in an increase in the content of immunoglobulins G (p<0,001, p<0,001) and M (p<0,001, p<0,001)), a pronounced increase in the content of immunoglobulin E (p<0,001, p<0,001) in the absence of significant changes in the content of immunoglobulin A and circulating immune complexes in the blood serum. Upon the onset of clinical remission in the first group of patients with allergic rhinitis receiving complex conventional therapy (Table 3), high levels of immunoglobulins G (p<0,001), M (p<0,001) and E (p<0,001) were recorded in the absence of significant changes in the content of immunoglobulin A and circulating
immune complexes in the blood serum. In the second group of patients with allergic rhinitis who received complex treatment in combination with ozone therapy (Table 3), during clinical remission, only an increase in the content of immunoglobulin E (p<0,001) was noted, whereas the content of immunoglobulins G, A, M and circulating immune complexes in blood serum did not differ from their content in blood serum practically healthy children of the control group.
In the first and second groups of patients with persistent allergic rhinitis during the period of exacerbation of the disease (Table 3) there was an increase in the phagocytic activity of neutrophils (p<0,01, p<0,001) with a decrease in the values of the phagocytic index (p<0,05, p<0,05) and the NCT-test (p<0,001, p<0,001). During clinical
remission, in the first group of patients with allergic rhinitis receiving complex conventional therapy (Table 3), an increase in the phagocytic activity of neutrophils (p<0,01)) was maintained with a decrease in the values of the phagocytic index (p<0,01) and the NCT-test (p<0,05), whereas in the second group of patients with allergic rhinitis receiving complex treatment in combination with ozone therapy (Table 3), phagocytic activity of neutrophils, phagocytic index and NCT-test values did not differ significantly from phagocytosis indicators in practically healthy children of the control group.
In the first group of children with moderate persistent allergic rhinitis who received complex conventional therapy, 3,9±0,3 months after the onset of clinical remission, signs of an exacerbation of the disease reappeared. In the second group of children with moderate persistent allergic rhinitis, who, along with complex conventional treatment, underwent two courses of ozone therapy with an interval of three months between them, clinical signs of an exacerbation of the disease were not recorded for 9,3±0,2 months. Thus, the duration of clinical remission in the second group of patients with allergic rhinitis exceeded 2.4 times (p<0,001) its duration in the first group of patients with allergic rhinitis.
Conclusions
1. The inclusion of ozone therapy in the comprehensive treatment of preschool and primary school children suffering from moderate persistent allergic rhinitis ensures a faster onset of complete clinical remission.
2. During the period of clinical remission, normalization of most parameters of immunological reactivity was recorded in the second group of patients with allergic rhinitis who received complex treatment in combination with ozone therapy, unlike patients of the first group who received only complex conventional therapy.
3. The repeated course of complex treatment in combination with ozone therapy (three months after the first course) in the second group of patients with allergic rhinitis ensures the preservation of complete clinical remission, the duration of which exceeds its duration in the first group of patients with allergic rhinitis.
4. The high clinical, immunomodulatory and antirelapse effects of ozone therapy allow us to recommend its widespread use in a complex of therapeutic measures for persistent allergic rhinitis in children.
Conflict of interest. The authors declare that there is no obvious or potential conflict of interest associated with the publication of the article.
Financing. The study had no sponsorship
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УДК 616.311.2-002:616.314-089.23:615.831+616.432.008 DOI 10.24412/2220-7880-2024-3-17-22
ОЦЕНКА ЭФФЕКТИВНОСТИ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ ДЛЯ ПРОФИЛАКТИКИ ГИНГИВИТА ПРИ ОРТОДОНТИЧЕСКОМ ЛЕЧЕНИИ ПОДРОСТКОВ С ГИПОТАЛАМИЧЕСКИМ СИНДРОМОМ ПУБЕРТАТНОГО ПЕРИОДА
Колесник К. А., Белоусова А.М.
Ордена Трудового Красного Знамени Медицинский институт имени С. И. Георгиевского ФГАОУ ВО «КФУ им. В. И. Вернадского», Симферополь, Россия (295051, г. Симферополь, бульвар Ленина, 5/7), e-mail: office@ma.cfuv.ru
Цель: оценить клиническую эффективность фотодинамической терапии для профилактики рецидивов гингивита при ортодонтическом лечении подростков с гипоталамическим синдромом пубертатного периода (ГСПП). Материал и методы: выполнили проспективное, открытое, рандомизированное, контролируемое
