Evaluating Changes in the Clinical Presentation of Acute Obstructive Bronchitis in Preschool Children Using Antiviral Therapy

A randomized double-blind controlled study was carried out to evaluate changes in the clinical presentation of acute obstructive bronchitis in preschool children using antiviral, anti-inflammatory therapy. The study enrolled 54 subjects (aged 3-6 years old) hospitalized with verified diagnosis of acute obstructive bronchitis. Their parents had given their informed consent for participation. Group 1 (n=26) received etiotropic therapy with the drug having complex antiviral, anti-inflammatory and antihistamine effect (Ergoferon), group 2 (n=28) received placebo. Meanwhile all children received complex therapy of ARI. To evaluate therapeutic efficacy the following parameters were compared: time to elimination of the clinical manifestations of the disease; extent of alleviation of the key symptoms, incidence of wheezing episodes and complications. Results. According to PCR, rhinoviruses prevailed in both groups in oropharyngeal swabs (31% in group 1 and 57% in group 2); furthermore, RNA of influenza B virus, respiratory syncytial virus, parainfluenza virus types 2 and 4 and metapneumovirus were also detected; 3 children in each group simultaneously had RNA of various viruses; no differences between the groups were observed. In group 1 average duration of increased body temperature (morning measurement) was 1.6 (1.4-1.9)±0.6 days, respectively, and all children reached normal values of morning and evening body temperature by the end of 3-day therapy. In group 2 morning body temperature reached normal values on types 2.7 (2.1-3.3)±1.2 days, respectively ( ü-test, P=0.002), while complete normalization in all children took place on day 6 of the follow-up. Area under curve for daily body temperature was statistically lower in group 1: 514.3 (513.8-514.9)±1.4 (°С x days) vs. 516.3 (515.1-517.5)±2.5(°C x days) in group 2 (U-test, P=0.002). Intoxication in group 1 was eliminated within 2.8 (2.5-3.1)±0.80 days on average, in group 2 - within 4.5 (4.1-4.8)±0.96 days (P<0.001). Intensity of catarrhal symptoms (nasal congestion, rhinitis, cough) resolved faster in group 1 (P<0.05). Average elimination term for catarrhal symptoms was 6.0 (5.7-6.3)±0.8 days vs. 9.0 days for groups 1 and 2 (P<0.001), respectively. Wheezing resolved within 4.1 (4.0-4.2)±0.3 days on average in group 1 and within 6.9 (6.7-7.0)±0.4 days in group 2 (P<0.001). Despite the treatment, eight children in group 2 showed moderate reinforcement of wheezing within the first 3-4 days of therapy, 3 of them had body temperature increased to subfebrile values requiring antibacterial treatment. Neither of children in group 1 had any bacterial complications or reinforced wheezing. All children from group 1 had complete recovery on day 8. Neither of subjects recovered completely on day 9 in group 2. Average recovery term in group 1 was 6.0 (5.7- 6.3)±0.8 days vs. 9.0 days in group 2 (P<0.001). No adverse effects associated with the medicinal products were recorded during the study. Average rating of therapeutic efficacy by the investigator using CGI scale was 3.7 (3.5-3.8)±0.49 scores in group 1 vs. 2.6 (2.3-2.9)±0.69 scores in group 2 (P<0.005). Rating of wheezing therapy efficacy was similar: 3.7 (3.4- 3.9)±0.57 and 2.2 (1.7-2.7)±1.29 for groups 1 and 2, respectively. Safety of the products according to CGI scale reached maximum in both groups. Parents' rating of the treatment in group 1 was 50% higher as compared to group 2: 3.6 (3.4- 3.8)±0.57 scores and 2.5 (1.8-2.9)±1.31 scores (P<0.005). Conclusion. Ergoferon in complex therapy of acute obstructive bronchitis in preschool children ensures rapid therapeutic effect including elimination of wheezing symptoms, prevention of bacterial complications, wheezing progression and is well tolerated by the subjects.

acute respiratory infections, acute obstructive bronchitis, wheezing, antiviral therapy, anti-inflammatory antihistamine therapy, Ergoferon, preschool children, PCR, randomised double blind placebo-controlled clinical trials

1. Инфекционная заболеваемость в Российской Федерации за январь-октябрь 2016 г. [Электронный ресурс] Режим доступа: http://www.rospotrebnadzor.ru/activities/statistical-materials/static-tic_details.php?ELEMENT_ID=7399 (дата обращения: 22.11.2016)

2. Инфекционная заболеваемость в Российской Федерации за январь-декабрь 2015 г. [Электронный ресурс] Режим доступа: http://www.rospotrebnadzor.ru/activities/statistical-materials/statictic_ details.php?ELEMENT_ID=5525 (дата обращения: 09.11.2016)

3. Волков И. К. Дифференциальная диагностика бронхообструктивного синдрома у детей. МНС. 2013; 1: 48: 125-128

4. Beigelman A., Bacharier L.B. Infection-induced wheezing in young children. J Allergy Clin Immunol 2014 Feb; 133: 2: 603-604.

5. Sun H., Sun Q., Jiang W. et al. Prevalence of rhinovirus in wheezing children: a comparison with respiratory syncytial virus wheezing. Braz J Infect Dis. 2016 Mar-Apr; 20: 2: 179-183.

6. Garcfa-Garcfa M.L., Calvo C., Falcon A. et al. Role of emerging respiratory viruses in children with severe acute wheezing. Pediatr Pulmonol 2010 Jun; 45: 6: 585-591.

7. Gern J.E. Virus/allergen interaction in asthma exacerbation. Ann Am Thorac Soc 2015 Nov; 12: Suppl 2: S137-43.

8. Busse W.W., Lemanske R. F., Gern J.E. The role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010 September 4; 376: 9743: 826-834.

9. Ritchie A.I., Jackson D.J., Edwards M.R. et al. Airway epithelial orchestration of innate immune function in response to virus infection. A Focus on Asthma. Ann Am Thorac Soc 2016 Mar; 13: Suppl 1: S55-63.

10. Kim T.K., Bheda-Malge A., Lin Y. et al. A system approach to understanding human rhinovirus and influenza virus infection. Virology. 2015 Dec; 486: 146-157.

11. El Saleeby C.M., Bush A.J., Harrison L.M. et al. Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children. J Infect Dis 2011 Oct 1; 204: 7: 996-1002.

12. Liesman R.M., Buchholz U.J., Luongo C.L. et al. RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction. J Clin Invest 2014; 124: 2219-2233.

13. Baraldo S., Contoli M., Bazzan E. et al. Deficient antiviral immune responses in childhood: distinct roles of atopy and asthma. J Allergy Clin Immunol 2012; 130: 1307-1314.

14. Busse W.W., Lemanske R. F., Gern J.E. The role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010 September 4; 376: 9743: 826-834.

15. Зайцева С.В. Особенности терапии бронхообструктивного синдрома у детей с острыми респираторными инфекциями. Практическая пульмонология. 2013; 1: 9-14.

16. Hayden F.G. Newer influenza antivirals, biotherapeutics and combinations. Influenza and Other Respiratory Viruses 2013; 7: 63-75

17. Hui D.S., Lee N., Chan P.K. Adjunctive therapies and immunomodulatory agents in the management of severe influenza. Antiviral Res 2013; 98: 410-416.

18. Becker T.M., Durrani S.R., Bochkov Y.A. et. al. Exogenous interferons reduce rhinovirus replication and alter airway inflammatory responses. Ann Allergy Asthma Immunol 2013; 111: 5: 397-401.

19. Инструкция по медицинскому применению препарата Эргоферон. [Электронный ресурс] Режим доступа: http://grls.rosminzdrav. ru/Grls_View_v2.aspx?idReg=135031&t=, свободный (Дата обращения: 09 11.2016).

20. Журавлёва М.В., Каменева Т. P., Черных Т. М. и др. Сравнительная характеристика ряда препаратов для лечения острой респираторной вирусной инфекции и гриппа. Доктор.Ру. 2015; 13: 114: 12-19

21. Усенко Д.В. Эргоферон: результаты клинических исследований при ОРВИудетей. Практ педиат 2015; 4: 66-70

22. Rafalsky V., Averyanov A., Bart B. et al. Efficacy and safety of Ergoferon versus oseltamivir in adult outpatients with seasonal influenza virus infection: a multicenter, open-label, randomized trial. Int J Infect Dis 2016 Oct; 51: 47-55.

23. Шиловский И.П., Корнилаева Г.В., Хаитов M.P. Новые возможности в терапии респираторно-синцитиальной вирусной инфекции: данные доклинического исследования препарата Эргоферон. Иммунология 2012; 33: 3: 144-148.

24. Шиловский И.П., Прозорова М.С., Хаитов M.P. Способность препарата Эргоферон подавлять инфицирующую активность респираторно-синцитиального вируса in vitro. Иммунология. 2015; 36: 4: 216-219

25. Кондюрина Е.Г., Заплатников А.Л., Елкина Т.Н. и др. Многоплановая оценка схем терапии острых респираторных инфекций в условиях рутинной педиатрической практики. Антибиотики и химиотер 2016; 61: 5-6: 8-20

26. Секирина М.А., Тарасов С.А., Горбунов Е.А. и др. Новые возможности в терапии бронхиальной астмы с использованием препаратов, содержащих релиз-активные антитела. IX Всероссийская конференция «Химия и медицина» с молодежной научной школой по органической химии. Уфа, 2013;108-109

27. Сабитов А.У., Ершова А.В. Оптимизация лечения острой респираторной вирусной инфекции у детей с бронхиальной астмой. Практ мед 2015; 2: 87: 85-90