Efficacy of Human Interferon Alpha-2b Spray Combined with Chiqiao Qingre Granule in the Treatment of Herpangina in Children

*Corresponding Author:

Anming Xie
Department of Emergency Medicine, Jiangxi Provincial Children’s Hospital, Nanchang, Jiangxi 330006, China
E-mail: Xieam76@163.com

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms

Abstract

The objective of this study was to evaluate the efficacy and safety of treating herpangina in children using interferon alpha-2b spray combined with Chiqiao Qingre granule. Over a period from January 2021 to December 2022, 240 children with herpangina who were treated at our hospital were randomly divided into four groups; group A received routine treatment, group B was treated with interferon alpha-2b, group C was treated with Chiqiao Qingre granule, and group D was treated with a combination of interferon alpha-2b and Chiqiao Qingre granule. The symptom regression time, serum inflammatory levels, and adverse reactions were observed and compared for 5 d. Interferon alpha-2b, Chiqiao Qingre granule and their combination treatment group all achieved better curative effect, and the combination of interferon alpha-2b and Chiqiao Qingre granule could bring better results, and the difference was not significant in the safety between combined treatment and routine treatment, interferon alpha-2b and Chiqiao Qingre granule alone. The combination of interferon alpha-2b and Chiqiao Qingre granule is an effective and safe therapy for children.

Keywords

Interferon alpha-2b, Chiqiao Qingre granule, herpangina, combined therapy, curative effect

In today's society, herpangina is one of the most common respiratory infections in children. It is mainly caused by coxsackievirus and often occurs during the summer and autumn[1,2]. The symptoms of the disease are significant, including sore throat, itchy throat, recurrent fever and more. In severe cases, herpangina can lead to complications such as shortness of breath and laryngeal edema, which can endanger the lives of children[3,4]. Unfortunately, conventional antiviral drugs have limited effects and may lead to drug resistance and adverse reactions[5]. However, researchers have recently begun to explore new treatments for this disease. Human Interferon-Alpha 2b (IFN-α2b) is a biological recombinant preparation that has been widely used for treating various viral infections and malignant tumors, making it an attractive treatment option for herpangina in children[6-9]. IFN-α2b cannot only inhibit virus replication but also regulate the immune system’s response and promote apoptosis after virus infection. In addition, Chiqiao Qingre granule is a compound preparation of traditional Chinese medicine that contains Schizonepeta tenuifolia, Forsythia suspensa, Fructus Aurantii, peppermint, Radix isatidis, ejiao and other ingredients. It has been shown to dispel pathogens and heat, clear away heat and detoxification, cool blood and stop bleeding. It also plays a role in treating upper respiratory tract infections in children[10-12]. Chiqiao Qingre granule can reduce the inflammatory reaction in the body, shorten the duration of disease, and improve patient’s clinical symptoms[13]. Many researchers have tried to combine IFN-α2b and Chiqiao Qingre granule to treat herpangina in children, and the efficacy of this combination has been verified in clinical studies. Compared with a single drug, using this combination of drugs can improve the cure rate, shorten the duration of clinical symptoms and reduce the occurrence of complications. Therefore, the purpose of this study is to evaluate the efficacy and safety of using IFN-α2b spray combined with Chiqiao Qingre granule to treat herpangina in children. This research provides a unique treatment idea for standardized treatment, improving the cure rate of herpangina and improving the quality of life for children. Over a period from January 2021 to December 2022, 240 children with herpangina who were treated at our hospital were randomly divided into four groups according to the clinical and diagnostic expert consensus of herpangina (version 2019)[14]. B was routine treatment group; C was IFN-α 2b group and D was Douqiao Qingre granule group (n=60). IFN-α2b combined with soy forsythia Qingre granule group (n=60). The difference in age, physique and serum inflammatory level among the three groups was not significant (p>0.05). This study was conducted with the approval of the hospital ethics committee, and the informed consent forms were signed by the guardians of the participating children. Inclusion criteria including the children aged between 1 mo and 5 y old; confirmed diagnosis of herpangina; informed consent provided by the parents or guardians; complete clinical data available and children who can cooperate with related clinical treatments, such as throat sprays or nebulized inhalation therapy. Exclusion criteria including the children with congenital heart disease, liver or kidney dysfunction; children with mental disorders; children with bacterial infections; children who have contraindications for the IFN-α2b spray and Chiqiao Qingre granule and children who have taken antiviral drugs recently. Routine treatment group including the hypothermia, fluid replacement, nutritional support and other symptomatic treatment; IFN-α2b group, in addition to routine treatment, IFN-α2b spray (Jiefu, Tianjin unknown organism, specification 10 ml:1 million IU, 120 spray), 1-2 spray/time, 3 d, continuous treatment for 5 d. In Chiqiao Qingre granule group, Children's Chiqiao Qingre granule was added on the basis of routine treatment (Jichuan Pharmaceutical Group Co., Ltd., specification 2 g). The usage of the medication is as follows; for children aged (1-3) y, 2-3 g; for children aged (4- 5), 3-4 g and taken with boiled water, 3 times a day for 5 d. In IFN-α2b combined with Chiqiao Qingre granule group; IFN-α2b and Chiqiao Qingre granule were added on the basis of routine treatment, the method was the same as before, for 5 d. The treatment conditions of the four groups were compared from the following aspects; symptom relief time, observed symptoms included; antipyretic time, salivation disappearance time, sore throat disappearance time, ulcer and herpes disappearance time; inflammatory factors Interleukin (IL)-6 and C-Reactive Protein (CRP); serum IL-6 was detected by Enzyme-Linked Immunosorbent Assay (ELISA), CRP was detected by immune transmission turbidimetry and adverse reactions such as nausea, rash and somnolence occurred during treatment. According to the evaluation of the children's symptoms including the cured; body temperature returned to normal within 3 d after treatment, sore throat completely disappeared, ulcers and herpes disappeared completely. In effective; body temperature returned to normal range within (3-5) d after treatment. Ulcer and herpes basically disappeared. In ineffective; after 5 d of treatment, there was still fever, no significant improvement in pharynx pain, ulcers and herpes did not disappear. Total effective rate=(cured+effective)/total number of cases×100 %. Statistical Package for the Social Sciences (SPSS) 25.0 software was utilized for statistical analysis. Measurement data were presented as mean±standard deviation, and oneway Analysis Of Variance (ANOVA) was performed to compare between groups. Post-hoc pairwise comparisons between groups were conducted using the Student–Newman–Keuls (SNK)-q test. Counting data were expressed as frequency/rate (%) and analyzed using the Chisquare (χ²) test. Statistical significance was set at p<0.05. The overall treatment effectiveness rate in group D was significantly higher than in group A, B, and C (p<0.05), while the effectiveness rate in group B and C were higher than in group A (p<0.05) as shown in Table 1. The duration of antipyretic therapy, disappearance of salivation, disappearance of throat pain, and the healing of ulcers and herpes in group D were significantly shorter than in the other three groups (p<0.05). Meanwhile, the antipyretic time, salivation disappearance time, pharyngitis disappearance time, and ulcer and herpes disappearance time in groups B and C were also shorter than in group A (p<0.05) as shown in Table 2. Following treatment, the serum inflammatory levels in group B, C and D were significantly lower compared to group A (p<0.05). Furthermore, group D had a lower level of inflammation compared to group B and C (p<0.05) as shown in Table 3. The incidence of adverse reactions in groups A, B, C and D was similar, and the difference in the overall complication rate among the four groups was not significant (p<0.05) as shown in Table 4. In this study, we evaluated the efficacy of using IFN-α2b, Chiqiao Qingre granule and their combination in treating herpangina in children, and compared their effects with those of routine treatment. We found that, compared to conventional therapy, all three treatment groups had better therapeutic effects. Moreover, our results showed that combination therapy had the most significant effect. These findings highlight the importance of integrating Chinese and Western medicine in pediatric disease treatment. Our experiments confirmed previous studies' results in the effectiveness of IFN-α2b. For instance, Fu et al.[15] observed a significant decrease in body temperature, pain relief, and a significant decrease in the level of inflammatory mediators after treating herpangina in 200 children with IFN-α2b. Similarly, in a multicenter randomized controlled study of 180 children with herpangina, Pan et al. concluded that IFN-α2b significantly improved clinical efficacy, shortened the course of the disease, and reduced the incidence of complications. Our findings reinforced these previous results, supporting the efficacy of IFN-α2b. Studies of Chiqiao Qingre granule's efficacy in treating respiratory tract infections in children have also produced similar results. For example, Zhang et al.[16] found that Chiqiao Qingre granule was more effective in alleviating upper respiratory tract infection symptoms in children, with better safety profiles. Yang et al.[17] studied 132 children with upper respiratory tract infections and reported shorter recovery times in body temperature and significant improvements in clinical symptoms in the treatment group. Another study discovered that Chiqiao Qingre granule effectively improved the course of upper respiratory tract infection, clinical symptoms, and inflammatory indicators in children[18]. Our experimental results are consistent with these previous studies, indicating that Chiqiao Qingre granule is effective in treating respiratory diseases and herpangina in children. Our study further found that the combination therapy significantly decreased the serum inflammatory markers IL-6 and CRP compared to the other three groups. This finding indicates that the combination therapy effectively reduced inflammation levels and improved immunity in children. It is similar to the results of previous studies by Jia et al. and Li et al., who found that the combination of Western medicine improved clinical symptoms of children with herpangina, reduced inflammation and improved immune function[19,20]. However, this study has some shortcomings and limitations. The sample size may not be huge enough and lack sufficient randomness. Data verification from multiple centers is necessary to examine empirical results' reliability. Furthermore, due to the subjects being children, it is challenging to evaluate adverse reactions and drug safety data, particularly for IFN-α2b. Long-term use may produce side effects; thus, safety studies require longer monitoring. In conclusion, this study indicates that using human IFN-α2b, Chiqiao Qingre granule, or their combination is effective in treating herpangina in children, providing a promising new treatment option. Future studies should continue to explore the effects of combining Chinese and Western medicine, and examine the potential of traditional Chinese medicine.

Table 1: Comparison of Clinical Efficacy of Children in Each Group (CASE %)

Table 2: Comparison of the Disappearance Time of Clinical Symptoms in Each Group

Table 3: Comparison of Inflammatory Levels in Children of Each Group after Treatment

Table 4: Comparison of Adverse Reactions among Children in Each Group

Conflict of interests:

The authors declared no conflict of interests.

References

1. Huang H, Li K, Cai Y. Clinical analysis of recombinant human interferon α-2b spray combined with Houttuynia cordata in the treatment of herpangina in children. Chin J Med 2021;6(14):3.
2. Pan J, Yang Z, Pan J. Efficacy and safety of recombinant human interferon α-2b oropharyngeal spray in the treatment of herpangina. Chin J Pract Pediatr 2020;35(4):6.
3. Chen L, Zhao W, Sun Y. Effects of Lanqin oral liquid combined with interferon α1b injection on inflammatory factors and humoral immunity in children with herpangina. Hainan Med J 2021;32(23):4.
4. Kang D. Analysis of clinical effect of Lanqin oral liquid combined with Kaihoujian spray in the treatment of herpangina in children. Heilongjiang Sci 2021;12(10):2.
5. Jiang R. Interpretation of expert consensus on diagnosis and treatment of herpangina. Western Med 2019;31(12):4.
6. Jiangnan F. Efficacy and safety of recombinant human interferon α-2b spray in the treatment of herpangina. Chin Med Innov 2020;17(30):4.
7. Wang X, Zhang X, Wang H. Study on the efficacy and safety of nebulized recombinant human interferon α-2b in the treatment of herpangina in children. Biomed Eng Clin 2015;5:44-9.
8. Xiao J, Wang M, Zhang X. Clinical effect of recombinant human interferon-A1b in pediatric herpangina. Strait Pharm 2018;30(6):3.
9. Wang J. Clinical analysis of atomized inhalation of recombinant human interferon α-1b combined with Kaihoujian spray in the treatment of herpangina in children. Chin Foreign Med 2018;37(16):3.
10. Wang Y, Wu L, Xu Y. Study on the efficacy and safety of Chiqiao Qingre granule in the treatment of acute upper respiratory tract infection in children. Chin J Epidemiol 2018;28(14):4.
11. He P, Su Z, Qin C. Clinical observation of Xiaoer Chiqiao Qingre granule combined with azithromycin in the treatment of recurrent respiratory tract infection in children. Guangxi Med J 2019;41(7):3.
12. Ding Y, Yan Y, Wu L. Analysis of clinical effect of Xiaoer Chiqiao Qingre granule on children with viral upper respiratory tract infection. Chin J Epidemiol 2014;24(20):3.
13. Zhang C, Liu Q, Yang J. Clinical efficacy of Xiaoer Chiqiao Qingre granule combined with interferon in the treatment of herpangina and its effect on serum inflammatory factors. Heilongjiang Med 2023;36(1):3.
14. Infection group of Chinese medical pediatrics association, national center for medical quality control of infectious diseases. Expert consensus on diagnosis and treatment of herpangina (2019 ed). Chin J Pediatr 2019;57(3):4.
15. Fu J, Zhang Y, J, Zhang N, Shi B. Observation on the effect of α-2b interferon atomization in the treatment of herpangina. J Commun Med 2020;21:4.
16. Zhang L. Observation on the improvement of symptoms and total efficacy of Xiaoer Chiqiao Qingre granule in the treatment of viral upper respiratory tract infection in children. Chin J Health Med 2020;518(9):159.
17. Yang S. Analysis of the value of Xiaoer Chiqiao Qingre granule in the treatment of upper respiratory tract infection in children. Chin Commun Phys 2019;35(23):2.
18. Li C. Clinical observation of Xiaoer Chiqiao Qingre granule in the treatment of acute upper respiratory tract infection. Chin Grass Roots Med 2019;26(3):4.
19. Jia Y, Duan Q, Zhang C. Clinical study of Xiaoer Chiqiao Qingre granule combined with Reduning injection in the treatment of infantile herpangina. Mod Med Clin 2019;4:5.
20. Li J, Wang B, GE L. Efficacy of Xiaoer Chiqiao Qingre granule combined with oseltamivir phosphate granule in the treatment of influenza in children and its effect on inflammatory factors. Chin J Emerg Med 2021;30(6):3.