CC BY
28
UDC 616.248-053.4(571.15)
BRONCHIAL ASTHMA IN CHILDREN OF PRESCHOOL AGE
1 Altai State Medical University, Barnaul
2 Siberian State Medical University, Tomsk
N.V. Shakhova1, E.M. Kamaltynova2, Yu.F. Lobanov1, T.S. Kashinskaya1
It is necessary to study the prevalence and risk factors of bronchial asthma (BA) among pre-school children in order to develop a disease prevention strategy. Objective. Our aim was to study the prevalence, clinical and allergological features and risk factors for BA in pre-school children living in urban settings of Altai Krai. Methods. There was conducted a cross-sectional study comprising 3205 children (age 3 to 6 years). At the screening stage, there were included children attending pre-school educational institutions in 5 cities of Altai Krai. BA symptoms were determined using the ISAAC questionnaire. On clinical stage, asthma was diagnosed based on criteria according to Global Initiative for Asthma (GINA) guideline. The prevalence of BA in urban children aged 3-6 years was 5.7%. 62.7% of them were previously diagnosed with BA. Most children - 59.4% had a mild severity BA. Sensitization was detected in 70 percent of children with BA. Most often, there was established sensitization to house dust mites Dermatophagoides pteronyssinus (63.3%), birch pollen (46.6%) and cat fur (31.1%). The risk factors for BA were family history of allergies [odds ratio (OR) 3.2; 95% confidence interval (CI) 2.2-4.6], masculine (OR 2.2, 95% CI 1.5-2.3), preterm birth (OR 2.1, 95% CI 1.3-3.3), smoking parents (OR 1.6, 95% CI 1.2-2.9), (OR 1.8, 95% CI 1.2-2.8), contact with animals in the first year of life (OR 1.4, 95% CI 1.0-2.0). Conclusion. The prevalence of BA was 7.7. Most often detected sensitization to house dust mites, birch pollen and cat fur. The risk factors for BA are family history of allergies, masculine, preterm birth, passive smoking and contact with animals in the first year of life.
Key words: children, bronchial asthma, ISAAC, prevalence, allergens, risk factors.
Bronchial asthma (BA) is one of the most common chronic diseases, the prevalence of which among children grows in different regions of the world, which is a serious problem for the health care system and the economy of the country. [12]. Traditionally, data on the prevalence of asthma among children is based on the results of the international epidemiological study "International Study of Asthma and Allergies in Childhood" (ISAAC), which was focused on schoolchildren 6-7 and 13-14 years old. However, more than half of all cases of asthma begin in preschool age [3]. So far, no international epidemiological studies of BA among children of preschool age have been conducted, and only a few foreign national studies have been published, indicating a high prevalence of the disease among this age group. Thus, the prevalence of BA among children of preschool age in China is 21.6% [4], Italy - 15.0% [5], Japan -9.3% [6], Portugal - 17.1% [7]. BA among preschool children in Russia has not been studied yet. The lack of data on the prevalence and risk factors of BA in children of preschool age does not allow for the formation of a national strategy for early prevention of the disease.
Objective: to study the prevalence, clinical and allergological characteristics and risk factors of BA in children of preschool age living in urban areas of Altai Krai.
Materials and methods
A one-stage population-based study of the prevalence of BA among children of pre-school age
living in urban areas of Altai Krai was conducted. The study was approved by the local independent ethics committee of the Altai State Medical University of the Ministry of Health of Russia (protocol No. 11 dated 10.17.2014) and agreed with the Ministry of Education and Science of Altai Krai. The study began in September 2015, completed in April 2017.
Inclusion criteria:
• children aged 3-6 years;
• visit to the kindergarten;
• availability of informed voluntary consent of parents/legal representatives for the participation of children in the study.
The study consisted of 2 stages - screening and clinical. A block diagram of the study is presented in Figure 1.
The screening stage was conducted in preschool educational institutions in 5 of 11 cities of Altai Krai (Barnaul, Rubtsovsk, Biysk, Kamen'-na-Obi, Novoaltaisk; Figure 2).
By means of draw method, out of 356 preschool institutions located in these cities, 78 were selected: 45 - Barnaul, 8 - Novoaltaisk, 10 - Rubtsovsk, 5 -Kamen-na Obi, 10 - Biysk. At the screening stage, the presence of BA symptoms was established using the ISAAC questionnaire ("Asthma-like symptoms" module for children aged 7-8 years) [8]. The questionnaire was issued to parents/legal representatives of the child for self-completion during the parent meeting or at home. The participants of the study needed to answer the question: "In the past 12 months, did your child
have coarse wheezing breathing and whistlertype noise in the chest?". If the answer to this question was positive, the child was referred to the children with asthma symptoms. The results of the screening phase of the study were published by us earlier [9]. Children with asthma symptoms were sent to the clinical phase of the study for clinical and laboratory examination and confirmation of the diagnosis of asthma. Clinical stage procedures
BA diagnosis criteria
BA was diagnosed on the basis of diagnostic criteria of the Global Strategy for Asthma Management and Prevention international
included interviewing parents/representatives, clinical examination of patients, skin prick testing with extracts of household, epidermal, pollen and food allergens and/or study of specific IgE levels. The clinical stage of the study was conducted on the basis of the Altai State Medical University, the Ministry of Health of Russia, in the Department of Allergology and Immunology of the Clinical Children's Hospital No. 7 (Barnaul).
agreement (GINA, updated 2018) [10]: recurrent or persistent unproductive cough, including at night, during exercise, crying and in the absence of respiratory symptoms infections; recurrent
were conducted by allergy immunologists and
Figure 1 - Study Flow Chart.
Figure 2 - Map of the Altai Krai with cities.
coarse wheezes; respiratory stress or shortness of breath; efficacy of therapy with inhaled glucocorticosteroids.
Prick testing with allergens
The skin prick test procedure was carried out with 9 standardized extracts of household, pollen, epidermal and food allergens (Dermatophagoides pteronyssinus house dust mite, cat epithelium, dog epithelium, birch pollen, meadow grass pollen, wormwood pollen, cow's milk, chicken egg) from Allergopharma, Germany. Positive (histamine 10 mg/ml) and negative controls were used according to clinical guidelines [11]. The skin test was considered positive when a blister was formed at least 3 mm bigger than the negative control. By a negative value of the positive control, an in vitro study was performed - the determination of specific IgE in serum.
Specific IgE determination
The determination of specific IgE level to the above-mentioned allergens was carried out in the medical laboratory "Gemotest" (Moscow) by immunofluorescence method on a Phadia ImmunoCAP 250 automatic analyzer (Phadia AB, Thermo Fisher Scientific, Sweden).
Risk factors
To study the risk factors for developing BA, a questionnaire was used, containing questions about the presence of allergic diseases in both parents (bronchial asthma, allergic rhinitis, atopic dermatitis), duration of breastfeeding, prematurity, regular (at least once a week) contact of the child with the animal at first year of life, smoking mother during pregnancy, smoking parents in the presence of a child in the first year of life and now. The questionnaire was issued to parents/legal representatives of the child for self-filling at the screening stage.
Comorbid allergic diseases
At the clinical stage, comorbid allergic diseases were verified - allergic rhinitis (AR) and atopic dermatitis (AtD). AR was established on the basis of ARIA (2008) criteria [12]: by >2 symptoms of the disease (rhinorrhea, difficulty in nasal breathing, itching in the nasal cavity, repeated sneezing) for >1 hours and with a positive prick test and/or by specific IgE in blood> 0.35 kU/l to at least one allergen. The diagnosis of AtD was verified on the basis of modified Hanifin and Rajka diagnostic criteria [13].
Statistical analysis
The sample size was calculated using the Epi Info program version 7.2.2.6. (CDC, USA). Considering the number of children in Altai Krai at the age of 3-6 years at the time of the study - 92350 children, the expected prevalence of asthma symptoms among 3-6 year-old children is 11% (taking into account the data of published studies), and also taking into account the specified maximum permissible error 1,1% and 95% confidence interval (CI), the required
sample size was determined to be 3007. Based on the fact that the expected return of the questionnaires may be about 50%, it was planned to distribute 5306 questionnaires. Data analysis was performed using the statistical software package SPSS version 17.0 (IBM SPSS, USA). The prevalence of BA in the population was calculated by the formula:
A/N*B,
where A is the number of children who answered "Yes" to the questionnaire; N is the total number of children who answered the questionnaire at the screening stage; B - % of children with confirmed BA at the clinical stage.
The description of the quantitative variables is made with an indication of the arithmetic mean and standard deviation. To assess differences in frequency characteristics in the groups, the Pearson X2 test was used. Differences were considered statistically significant by p <0.05. To determine the risk factors for BA, odds ratios (OR) and 95% CI were calculated.
Results and discussion
Prevalence
According to the results of our study, the prevalence of BA among 3-6 year-old children was 5.7%. At the same time, out of 128 children diagnosed with asthma, only 86 (62.7%) had a diagnosis of asthma previously established in practical medical institutions. When analyzing the prevalence of asthma among different age groups, it was found that the prevalence of asthma among 3-4 year-old children was 5.1%, among 5-6 year-old children - 6.3%.
Clinical characteristics of patients with AR
The majority of children - 76 (59.4%) had a mild severity BA, 50 (39.1%) children had a moderate severity BA, and 2 (1.5%) children had a severe BA. Of 128 children with asthma, 82 (64.1%) were diagnosed with comorbid allergic diseases, of them 52 (40.6%) children were diagnosed with AR, 6 (4.7%) had AtD, 24 (18.8%) children - AR and AtD.
Sensitization spectrum
During an allergological examination, out of 128 children, sensitization was detected in 90 (70.3%), of which 39 (43.3%) were sensitized to one allergen, 51 (56.7%) - to two or more allergens. Sensitization was most often detected to Dermatophagoides pteronyssinus house dust mite - 57 (63.3%) children, birch pollen - 42 (46.6%) children, cat epithelium -28 (31.1%) children. Less commonly, sensitization to the epithelium of the dog was determined - 13 (14.4%) children, pollen from wormwood - 18 (20.0%) and meadow grass pollen - 14 (15.5%) children. 19 (21.1%) children had sensitization to food allergens, of which 15 (16.6%) - to chicken egg protein, 13 (13.3%) - to cow's milk.
AR risk factors
High risk of BA development at preschool age is associated with male gender, burdened by allergic diseases, family history, prematurity, contact with animals in the first year of life, passive smoking
(Table 1). There is no statistically significant relationship between asthma and short duration of breastfeeding (<6 months), mother smoking during pregnancy and passive smoking in the 1st year of life.
Table 1
BA risk factors in 3-6 year-old children
Risk factors Children with BA (n=128) Children without BA (n=2970) OR (95% CI) P
Male gender 90 (70,3%) 1517 (51,0%) 2,2 (1,5-2,3) 0,000
Burdened family allergic history 70 (54,6%) 808 (27,2%) 3,2 (2,2-4,6) 0,000
Allergic diseases of the father 36 (28,1%) 353(11,8%) 2,9 (1,9-4,3) 0,000
Allergic diseases of the mother 44 (34,3%) 564 (18,9%) 2,2 (1,5-3,2) 0,000
Prematurity 24 (18,7%) 294 (9,9%) 2,1 (1,3-3,3) 0,001
Breastfeeding <6 months 38 (34,5%) 866 (33,1%) 1,0 (0,7-1,5) 0,755
Contact with animals in the 1st year of life 74 (57,8%) 1440 (48,4%) 1,4 (1,0-2,0) 0,038
Mother's tobacco smoking during pregnancy 4 (3,1%) 58 (1,9%) 1,6 (0,5-4,5) 0,353
Tobacco smoking of parents in the 1st year of a child's life 16 (12,5%) 300 (10,1%) 1,2 (0,7-2,1) 0,379
Parents' tobacco smoking at the present time 22 (17,1%) 334 (11,2%) 1,6 (1,2-2,9) 0,039
Note: The analysis of risk factors did not involve the data on children with symptoms of asthma, whose parents refused to participate in the clinical part of the study.
The study showed a high prevalence of BA among urban children of Altai Krai at the age of 3-6 years - 5.7%, while only 62.7% of the children had a diagnosis of BA previously established in practical healthcare institutions. Most children have a mild degree of asthma, and the most significant inhaled allergens are house dust mites, birch pollen and cat epithelium. Risk factors for the development of asthma in preschool age are male gender, burdened allergy family history, prematurity, passive smoking, contact with animals in the first year of life.
We compared our data with the results of foreign epidemiological studies, since no such work was carried out in Russia (Table 2). The prevalence of BA among preschool children in Altai Krai is comparable to the prevalence of BA in Japan [6], China [16], India [17], Denmark [18], while in Portugal [7], Italy [5] and Sri Lanka [ 19], the prevalence of BA is much higher. Differences in prevalence rates may be associated with different methods for diagnosing BA. In all the analyzed studies, the prevalence of asthma was studied using questionnaires, and the diagnosis was made on the basis of subjective information - positive responses of parents, and therefore, the data obtained do not always correspond to the true prevalence of the disease in the studied population. This is confirmed by Hederos et al. [21], according
to which the prevalence of asthma studied using the questionnaire is higher compared with the prevalence of physically verified asthma. In our study, after screening by means of the ISAAC questionnaire, BA was verified by allergologists based on GINA criteria, which improves the accuracy of the results obtained. In addition, differences in the prevalence of BA between countries may be associated with the use of different questionnaires, the age heterogeneity of children and the climatic and geographical features of the countries.
According to our data, 70.3% of children with asthma at the age of 3-6 years are sensitized, of which 43.3% have sensitization to one allergen, 56.7% to two or more allergens. Our results are consistent with previously published studies. So, according to Onell et al. [22], 75% of children with asthma aged 6-18 years are sensitized, of which 48% are sensitized to 2 or more allergens, according to Ozkava et al. [23], sensitization was detected in 80.6% of children with severe BA at the age of 6-15 years. We found that the most significant inhaled allergen in asthma in preschoolers are house dust mites (Dermatophagoides pteronyssinus mite), to which 63.3% of children have sensitization. Similar indicators of sensitization to Dermatophagoides pteronyssinus mite in children with BA were obtained by Duenas-Mezaet al. [24] - 56.9%.
Table 2
Results of previously published studies of asthma prevalence in preschool children
Author Country Age, years Study method Prevalence, %
Kim et al. (2013) [14] Korea 3-6 ISAAC questionnaire 13,8
Cho et al. (2013) [15] Korea 2-6 ISAAC questionnaire 4,9
Broms (2013) [16] Sweden 1-6 ISAAC questionnaire 8,9
Branco et al. (2015) [7] Portugal 3-5 ISAAC questionnaire 17,1
Huang et al. (2015) [4] China 3-7 ISAAC questionnaire 21,6
Tang et al. (2015) [17] China 3-4 ISAAC questionnaire 7,6
Dhakar et al. (2015) [18] India 3-6 ISAAC questionnaire 9,2
Okada et al. (2015) [6] Japan 3-6 ISAAC questionnaire 9,3
Henrikse et al. (2015) [19] Denmark 3-6 questionnaire 9,8
Indinnimeo et al.(2016) [5] Italy 3-5 questionnaire 15,0
Seneviratne et al.(2018) 20] Sri Lanka 3-5 questionnaire 21,3
We found that the male gender, burdened family allergic history, prematurity, passive smoking and contact with animals during the first year of life increase the risk of developing BA, while the effect on the risk of developing BA of short duration of breastfeeding and smoking of the mother during pregnancy time is not established. The data obtained correspond to the previously published studies. Thus, according to Bao et al. [25] and Kutrova et al. [26], male gender increases the risk of developing BA at preschool age (OR = 1.7; OR = 2.0, respectively). According to a meta-analysis of 24 studies by Liu et al. [27], the burdened family allergic history is a significant risk factor for asthma in preschool years (OR = 4.6). Prematurity increases the risk of developing BA at preschool age, according to a meta-analysis of 24 studies by den Dekker et al. [28] and a meta-analysis of 31 studies by Sannensehein-van der Voort et al. [29] (OR = 1.4; OR = 1.3, respectively), and according to Leung et al. [30], prematurity increases the risk of hospitalization due to asthma among preschoolers. According to the results of our study, passive smoking and contact of a child with an animal in the first year of life increases the risk of developing BA in preschool children. The meta-analysis of 17 studies by Bao et al. [24] also revealed an increase in the risk of asthma at preschool age by passive smoking (OR = 1.5), and Huang et al. [4] found an increased risk of developing BA among children with a burdened family allergy history in contact with animals in the first year of life.
Conclusion
The study showed a high prevalence of BA among 3-6 year-old children living in urban areas of Altai Krai - 5.7%, while only 62.7% of children had a diagnosis of BA previously established in practical medical institutions. Most children have a mild degree of asthma, and the most significant inhaled allergens are house dust mites, birch
pollen and cat epithelium. Risk factors for the development of asthma in preschool age are male gender, burdened allergy family history, prematurity, passive smoking and contact with animals in the first year of life.
References
1. Pearce N, Ait-Khaled N, Beasley R [et al.]. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007; 62: 758-766. doi: 10.1136/thx.2006.070169
2. Van den Akker-van Marle ME, Bruil J, De-tmar SB. Evaiuation of cost of disease: assessing the burden of society in children in the European Union. Allergy. 2005; 60(2): 140-149. D0I:10.1111/j.1398-9995.2005.00692.x
3. Patelarou E, Tzanakis N, Kelly FJ. Exposure to indoor pollutants and wheeze and asthma development during early childhood. Int J Environ Res Public Health. 2015; 12(4): 3993-4017. doi: 10.3390/ijerph120403993
4. Huang C, Liu W, Hu Y [et al.]. Updated prevalences of asthma, allergy, and airway symptoms, and a systematic review of trends over time for childhood asthma in Shanghai, China. PLoS ONE. 2015; 10(4): e0121577. doi:10.1371/journal.pone.0121577.
5. Indinnimeo L, Porta D, Forastiere F. [et al.]. Prevalence and risk factors for atopic disease in a population of preschool children in Rome: Challenges to early intervention. International Journal of Immunopa-thology and Pharmacology. 2016; 29(2): 308-319.
6. Okada Y, Kumagai H, Morikawa Y [et al.]. Epidemiology of pediatric allergic diseases in the Ogas-awara Islands. Allergology International. 2016; 65: 3743. doi: 10.1016/j.alit.2015.06.010
7. Branco PTBS, Nunes RAO, Alvim-Ferraz MCM [et al.]. Asthma prevalence and risk factors in early childhood at Northern Portugal. Rev Port Pneumol. 2016; 22(3):146-150. doi: 10.1016/j.rppnen.2015.11.001
8. Gavrilov S.M. Standardized epidemiological studies of allergic diseases in children. (Adaptation of
the program "International Study of Asthma and Allergy" ISAAC "in Russia). Manual for doctors. M., 1998.
9. Shakhova N.V., Kamaltynova E.M., Loban-ov Y.F., Ardatova T.S., Nikolaeva K.S. Prevalence and risk factors of asthma-like symptoms and allergic rhinitis in preschool children. Russian Pulmonology. 2017;27(5):636-642. doi: 10.18093/0869-0189-201727-5-636-642
10. Global Initiative for Asthma. Global strategy for Asthma management and prevention. Global Initiative for Asthma (updated 2018) 2018. Avaliable at: https://ginasthma.org/2018-gina-report-global-strate-gy-for-asthma-management-and-prevention.
11. Heinzerling L, Mari A, Bergmann KC [et al.]. The skin prick test - European standards. Clin Transl Allergy. 2013; 3: 3. doi:10.1186/2045-7022-3-3
12. Bousquet J, Khaltaev N, Cruz AA [et al.]. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008; 63(86): 8-160.
13. Federal clinical guidelines for the diagnosis and treatment of atopic dermatitis. 27. M., 2013: 27.
14. Kim HY, Kwon EB, Baek JH [et al.]. Prevalence and comorbidity of allergic diseases in preschool children. Korean J Pediatr. 2013; 56(8): 338-342. doi:10.3345/kjp.2013.56.8.338
15. Cho YM, Ryu SH, Choi MS [et al.]. Asthma and allergic diseases in preschool children in Korea: findings from the pilot study of the Korean Surveillance System for Childhood Asthma. J Asthma. 2014; 51(4): 373-379. doi: 10.3109/02770903.2013.876648
16. Broms K, Norback D, Eriksson M [et al.]. Prevalence and co-occurrence of parentally reported possible asthma and allergic manifestations in preschool children. BMC Public Health. 2013; 13: 764. doi. org/10.1186/1471-2458-13-764
17. Tang SP, Liu YL, Wang SB [et al.]. Trends in prevalence and risk factors of childhood asthma in Fuzhou, a city in Southeastern China. J Asthma. 2015; 52(1): 10-15. doi: 10.3109/02770903.2014.952434
18. Dhakar AS, Kamath R, Pattanshetty S [et al.]. Prevalence of childhood asthma among 3-6 years old children, Udupi Taluk, Karnataka, India. Global Journal of Medicine and Public Health. 2015; 4(6).
19. Henriksen L, Simonsen S, Haerskjold A [et al.]. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy Clin Immunol. 2015; 136: 360-6. doi:10.1016/j. jaci.2015.02.003
20. Seneviratne R, Gunawardena NS. Prevalence and associated factors of wheezing illnesses of children aged three to five years living in under-served settlements of the Colombo Municipal Council in Sri Lanka: a cross-sectional study. BMC Public Health. 2018; 18(1): 127. doi: 10.1186/s12889-018-5043-3
21. Hederos CA, Hasselgren M, Hedlin G, Bornehag CG. Comparison of clinically diagnosed asthma with parental assessment of children's asthma in a ques-
tionnaire. Pediatr Allergy Immunol. 2007; 18(2): 13541. doi:10.1111/j.1399-3038.2006.00474.x.
22. Önell A, Whiteman A, Nordlund B [et al.]. Allergy testing in children with persistent asthma: comparison of four diagnostic methods. Allergy. 2017; 72(4): 590-597. doi: 10.1111/all.13047
23. Ozkaya E, Sogut A, Kügükkog M [et al.]. Sensitization pattern of inhalant allergens in children with asthma who are living different altitudes in Turkey. Int J Biometeorol. 2015; 59(11): 1685-90. doi: 10.1007/ s00484-015-0975-0
24. Duenas-Meza E, Torres-Duque CA, Correa-Vera E [et al.]. High prevalence of house dust mite sen-sitization in children with severe asthma living at high altitude in a tropical country. Pediatr Pulmonol. 2018; 53(10): 1356-1361. doi: 10.1002/ppul.24079
25. Bao Y, Chen Z, Liu E [et al.]. Risk Factors in Preschool Children for predicting asthma during the preschool age and the early school age: a systematic review and meta-analysis. Curr Allergy Asthma Rep. 2017; 17(12): 85. doi: 10.1007/s11882-017-0753-7
26. Kutzora S, Weber A, Heinze S [et al.]. Asthmatic wheezing phenotypes in preschool children: Influential factors, health care and urban-rural differences. Int J Hyg Environ Health. 2018; 221(2): 293-299. doi: 10.1016/j.ijheh.2017.12.001
27. Liu SJ, Wang TT, Cao SY [et al.]. A Meta analysis of risk factors for asthma in Chinese children. Zhongguo Dang Dai Er Ke Za Zhi. 2018; 20(3): 218-223.
28. Den Dekker HT, Sonnenschein-van der Voort AMM, de Jongste JC [et al.]. Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children. J Allergy Clin Immunol. 2016; 137(4): 1026-1035. doi: 10.1016/j.jaci.2015.08.050
29. Sonnenschein-van der Voort AM, Arends LR, de Jongste JC. Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children. J Allergy Clin Immunol. 2014; 133(5): 1317-1329. doi: 10.1016/j. jaci.2013.12.108230. Leung JY, Lam HS, Leung GM, Schooling CM. Gestational age, birthweight for gestational age, and childhood hospitalisations for asthma and other wheezing disorders. Paediatr Perinat Epidemiol. 2016; 30(2): 149-159. doi: 10.1111/ ppe.12273.
Contacts
Corresponding author: Shakhova Natalia Viktorovna, Candidate of Medical Sciences, Associate Professor, Department of Propedeutics of Children's Diseases, Altai State Medical University, Barnaul.
656038, Barnaul, Lenina Prospekt, 40.
Tel.: (3852) 619182.
Email: [email protected]
Author information
Kamaltynova Elena Mikhailovna, Doctor of Medical Sceinces, Associate Professor of the Department of Theoretical Pediatrics with a Course of Childhood Diseases of the Medical Faculty, Siberian State Medical University, Tomsk. 634050, Tomsk, Moskovsky Trakt, 2. Tel.: (3822) 909823. Email: [email protected]
Lobanov Yury Fedorovich, Doctor of Medical Sciences, Professor, Head of the Department of
Propedeutics of Children's Diseases, Altai State
Medical University, Barnaul.
656038, Barnaul, Lenina Prospekt, 40.
Tel.: (3852) 566895.
Email: [email protected]
Kashinskaya Tatyana Sergeevna, Assistant
Professor of Department of the Department of
Propedeutics of Children's Diseases, Altai State
Medical University, Barnaul.
656038, Barnaul, Lenina Prospekt, 40.
Tel.: (3852) 566895.
Email: [email protected]
