Clinical Study of Acupoint Application of Jiezi Fangxiao Ointment Combined with Pingchuan Prescription in the Treatment of Pediatric Asthma

Yuzhe REN, Zhou YU, Hong CHEN, Zeyi YANG, Xiangzheng YANG*

1. Shenzhen Hospital of Beijing University of Traditional Chinese Medicine (Longgang), Shenzhen 518100, China; 2. Heilongjiang University of Chinese Medicine, Harbin 150040, China; 3. Beijing University of Traditional Chinese Medicine, Beijing 100029, China

Abstract [Objectives] To study the clinical effect of Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription in the treatment of pediatric asthma. [Methods] A total of 40 children with asthma admitted to the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2017 to September 2018 were selected as the research subjects, and divided into control group and observation group according to random classification method, with 20 cases in each group. Among which the control group was given routine symptomatic treatment, the observation group was treated with Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription on the basis of the control group. After 4 weeks of continuous treatment, the clinical efficacy was observed and the changes of traditional Chinese medicine symptom scores, forced expiratory volume in the first second (FEV1), maximum expiratory flow (PEF), forced vital capacity (FVC), peripheral blood eosinophils (EOS) and interleukin-17 (IL-17) were compared between the two groups before and after treatment. [Results] After treatment, the traditional Chinese medicine(TCM) scores such as asthma, cough, expectoration, chest tightness, dyspnea and wheezing sound of lungs in the two groups were significantly improved, and the improvement in the observation group was superior to that in the control group. The difference was statistically significant (P<0.05). FEV1, PEF and FVC in the two groups were significantly improved after treatment, and the improvement in the observation group was superior to that in the control group. The difference was statistically significant (P<0.05); after treatment, the levels of EOS and IL-17 decreased in both groups, and the improvement in the observation group was superior to that in the control group, the difference was statistically significant(P<0.05). [Conclusions] The clinical effects of Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription in the treatment of infantile asthma were obvious, which can significantly improve the TCM symptoms scores, pulmonary function and immune function of patients.

Key words Pediatric asthma, Acupoint Application of Jiezi Fangxiao Ointment, Pingchuan Prescription, Traditional Chinese medicine syndrome scores, Lung function, Peripheral blood eosinophils, Interleukin-17, Clinical research

1 Introduction

Asthma is one of the common airway inflammatory diseases in children, its main clinical manifestations are shortness of breath, sputum, cough, dyspnea, and even the inability to lie down and other emergency symptoms during the attack, it has the characteristics of repeated attacks, prolonged and difficult to recover[1-2]. It is equivalent to the category of bronchial asthma and other diseases in modern medicine, it is thought that the pathogenesis of this disease is mainly related to airway hyperresponsiveness[3-4]. According to WHO statistics, the global death toll of asthma is about 34×104people every year, and the number of people with disabilities affecting their lives is about 10 million, moreover, according to China’s epidemiological statistics, the incidence of asthma in children is on the rise[5]. Especially for children, whose immunity is relatively low, clinical attention should be paid to the children with asthma, scientific and reasonable treatment methods should be selectively adopted to actively control the symptoms and reduce the attack of asthma[6]. While in modern medicine, glucocorticoid and β2receptor agonist are mainly used for symptomatic treatment of the disease, long-term use can only control symptoms, but the disease is not cured from the source, and there are still some toxic and side effects[7-8]. And the treatment of traditional Chinese medicine of asthma has a long history, and the theory is rich, the effect is exact, as Zhu Danxi in the Yuan Dynasty once said that the onset of children’s asthma has both internal causes and external factors; when asthma attacks, the treatment is mainly to dispel pathogenic factors, while when it does not attack, the treatment is mainly to support the vital qi, this treatment principle is put forward in the treatment of asthma, which provides a theoretical basis for the treatment of this disease in later generations[9-10]. In recent years, there have been many reports about the treatment of asthma with integrated traditional Chinese and western medicine, and the curative effect is remarkable. The purpose of this study was to explore the clinical efficacy of Acupoint Application of Jiezi Fangxiao Ointment combined with Pingchuan Prescription in the treatment of childhood asthma, so as to provide theoretical reference for the treatment of children with asthma by integrated traditional Chinese and western medicine.

2 Materials and methods

2.1 General materialsA total of 40 children with asthma admitted to the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2017 to September 2018 were selected as the research subjects, and divided into control group and observation group according to random classification method, with 20 cases in each group. In the control group, there were 8 males and 12 females, aged 5-13 years, with an average age of (7.32±1.06) years and an average course of disease of (3.53±2.06) days; in the observation group, there were 11 males and 9 females, aged 5-15 years, with an average age of (7.24±3.27) years, and an average course of disease of (3.60±1.83) d. There was no significant difference in general information between the two groups (P>0.05), which was comparable.

2.2 Diagnostic criteriaDiagnostic criteria of Western medicine: The guidelines for the diagnosis of children with asthma revised by the Respiratory Group of Pediatric Society of Chinese Medical Association in 2016 can be referred to[11]; Diagnostic criteria of traditional Chinese medicine: The consensus of TCM experts on tracheal asthma formulated by the Pulmonary Disease Branch of the China Association of Traditional Chinese Medicine in 2012 can be referred to[12].

2.3 Inclusion criteriaThose who meet the diagnostic criteria of Western medicine; those who meet the diagnostic criteria of Chinese medicine; the disease classification is mild, the classification criteria also refer to the diagnostic guidelines for children with asthma revised by the Respiratory Group of Pediatric Society of Chinese Medical Association in 2016. The consent of patients and their families must be obtained in advance.

2.4 Exclusion criteriaThose who do not meet the inclusion criteria; those who are participating in other drug trials and have recently used drugs; those who have recently suffered from acute upper or lower respiratory tract infection and are taking drugs; those who have a history of severe heart, brain, kidney, hematopoietic system and other organs; those who have mental diseases and are unable to cooperate.

2.5 Shedding and elimination criteriaThose who do not use drugs according to the required rules and treatment interruption and cannot determine the curative effect or incomplete information; those who have to adjust the treatment plan due to serious diseases during the enrollment period; those who have very poor patient compliance.

2.6 Therapeutic methodsThe control group was routinely given Montelukast Sodium Chewable Tablets, which were purchased from Hangzhou Moshadong Pharmaceutical Co., Ltd.( SFDA approval number: J20070058). Among them, children aged from 3 to 5 years were given 4 mg once and aged from 5 to 14 years were given 5 mg once a day for 4 weeks. On the basis of the control group, the observation group was additively treated with Pingchuan Prescription and Acupoint Application of Jiezi Fangxiao Ointment. Pingchuan Prescription was 5 g honey-fried Herba Ephedrae, 5 g bitter almond, 5 g Perilla Frutescens Seed, 5 g stir-baked Semen Raphani, 5 g peach kernel and 10 gScutellariabaicalensis, which was taken 4 doses a day, 4 times a day for 4 weeks; the Acupoint Application of Jiezi Fangxiao Ointment consisted of 7 kinds of herbs including white mustard seed, herba asari cum radice, lumbricus, herb ephedra,etc., which were all from the TCM Pharmacy of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine, they were ground into fine powder, mixed in proportion, boiled with ginger juice, cooled, mixed with an appropriate amount of egg white to form a paste, pressed into a medicine cake, and applied to Feishu and Dingchuan acupoints with sterile dressing and adhesive tape fixed, the dog days, namely, the most vigorous season of Yang Qi, were choose to apply, they were applied in the three days before the first of the three ten-day periods of the hot season, the three days before the second of the three ten-day periods of the hot season and the 11th, 12thand 13thd of the second of the three ten-day periods of the hot season, and the three days before the last of the three ten-day periods of the hot season, respectively, and 0.5-2.0 h per time, 12 d in total.

2.7 Observational indexes

2.7.1TCM syndrome scores. According toGlobalInitiativeforPreventionandTreatmentofAsthma(2006 edition)[13], the changes of wheezing, cough, expectoration, chest tightness, dyspnea and pulmonary wheezing scores before and after treatment were observed (Table 1).

Table 1 TCM syndrome scores

2.7.2Observation on the changes of pulmonary function before and after treatment. ST-250 pulmonary function instrument made in Japan was used, each index was repeated for 3 times, the mean value of each index was used to determine the forced expiratory volume (FEV1), maximum expiratory flow rate (PEF) and forced vital capacity (FVC) in the first second before and after treatment.

2.7.3Observation on the changes of eosinophil (EOS) and interleukin-17 (IL-17) in peripheral blood before and after treatment. For all children with EOS, 5 mL of elbow vein blood was collected under fasting state after getting up in the morning, and the serum levels of IL-17 were detected by enzyme-linked immunosorbent assay (ELISA). 5 mL of elbow vein blood was taken as before, and the operation was strictly in accordance with the operation standard of ELISA Kit (R & D Company of the United States) and then refrigerated for examination.

2.8 Criteria of curative effectThe criteria for judging the efficacy of TCM syndromes: Referring to theTCMGuidelinesfortheDiagnosisandTreatmentofPediatricAsthma[14]. Cure: The main clinical symptoms of wheezing disappeared without recurrence in the near future; markedly effective: the clinical symptoms were significantly relieved; there were still several attacks in the near future; effective: the symptoms were improved compared with those before treatment, but there were still wheezing and other symptoms after drug withdrawal; ineffective: the symptoms of wheezing and other symptoms did not decrease, but there was a trend of aggravation. Lung function and various laboratory indexes were improved in varying degrees.

3 Results

3.1 Comparison of TCM syndrome scores between the two groupsAfter treatment, the TCM syndrome scores of wheezing, cough, expectoration, chest tightness, dyspnea and lung wheezing in the observation group and the control group were significantly improved, and the decrease in the observation group was more obvious, the difference was statistically significant (P<0.05) (Table 2).

Table 2 Comparison of TCM syndrome scores between the two groups n=20)

3.2 Comparison of pulmonary function indexes between the two groupsAfter treatment, FEV1, PEF and other indicators of the two groups were significantly improved, the difference was statistically significant (P<0.05), compared with FVC of the control group, the difference was not statistically significant (P>0.05) (Table 3).

Table 3 Comparison of pulmonary function indexes between the two groups n=20)

3.3 Comparison of EOS and IL-17 levels between the two groups before and after treatmentAfter treatment, the levels of EOS and IL-17 in the two groups were significantly improved, and the decrease in the observation group was more obvious, the difference was statistically significant (P<0.05) (Table 4).

Table 4 Comparison of EOS and IL-17 levels between the two groups before and after treatment n=20)

4 Discussion

In modern medicine, it is considered that children’s asthma is a common pediatric disease caused by virus, bacteria, mycoplasma, chlamydia and other infections with respiratory system as the main symptom, the main clinical manifestations are recurrent wheezing, coughing and dyspnea, long-term unhealing leads to a decline of respiratory immune function, making the disease repeatedly protracted and difficult to heal, which will have adverse effects on the physical and mental health of children[15-16]. In this study, children with asthma were routinely given anti-inflammatory and antiasthmatic drug treatment, among which Montelukast Sodium Chewable Tablet is a commonly used leukotriene receptor anticancer agent, because it can competitively combine with leukotriene receptor, has high selectivity, and can effectively inhibit the inflammatory reaction, thus can reduce the high airway reaction of children[17]. However, there are many adverse reactions in the long-term application of Western medicine, traditional Chinese medicine has been paid more and more attention because of its definite curative effect and small adverse reactions. In traditional Chinese medicine, it is believed that the pathogenesis of asthma in children is mainly due to congenital deficiency of lung, spleen, kidney and other organs. The spleen mainly carries water and liquid, and if the spleen is not healthy, the phlegm will stop; the lung is a delicate organ, which is more susceptible to external evil, therefore, when external evil invades the lung, the impurity and phlegm remains stagnant, the phlegm heat will block the lung over time; the kidney is in charge of absorbing Qi and keeps the depth of breathing, the deficiency of kidney Qi leads to weakness of intake, shortness of breath and other symptoms. Therefore, the invasion of exogenous pathogens, improper diet, and the above-mentioned three visceral phlegm lead to the occurrence of symptoms such as lung Qi obstruction, airway obstruction, abnormal ventilation and descending of Qi, resulting in wheezing and coughing, therefore, the treatment should be based on the principle of treating the symptoms at the time of onset and treating the root cause at ordinary times. The Acupoint Application of Jiezi Fangxiao Ointment was made by Professor Zhang Wei according to the external application of white mustard seed inZhangShiYiTongwritten by Zhang Lu in Qing Dynasty; in the prescription, white mustard seed and ephedra are the monarch drugs, white mustard seed can warm and disperse, dissolve cold phlegm, and pass meridians, has the functions of warming lung, resolving phlegm, regulating Qi and dispersing stasis, ephedra has the effect of diffusing the lung to calm panting; asarum is the ministerial drug, which has the functions of warming lung and dissipating excessive fluid, dispersing cold and dredging orifices; Clove can warm kidney and depress Qi; the formula is also supplemented with Yanhusuo, earthworm, Chinese rhubarb, common monkshood mother root,etc., which can disperse cold, regulate Qi and relieve pain, and the whole formula plays the functions of warming lung and resolving phlegm, descending adverse Qi and relieving asthma, at the same time, it is applied in the dog days of summer when its Yang qi is the most vigorous, which is more conducive to the absorption of drugs[18]. Pingchuan Prescription is based on the unique experience of Xu’s pediatrics department summarized by Professor Yu Jian ’er who is a famous old Chinese medicine doctor in China, and his own clinical experience for decades, it has been clinically verified repeatedly and has definite curative effect. The prescription is composed of honey-fried Herba Ephedrae, stir-baked Semen Raphani, Semen Armeniacae Amarae,Perillafrutescensseed, peach kernel,Scutellariabaicalensis,etc. In the prescription, honey-fried Herba Ephedrae is the monarch drug, which has the effects of diffusing the lung and calming panting; Semen Armeniacae Amarae,P.frutescensseed and stir-baked Semen Raphani are ministerial drugs, which can lower Qi and reduce phlegm, relieve cough and asthma; peach kernel is also ministerial drug, which has the functions of activating blood and dissolving stasis; among which the combination of honey-fried Herba Ephedrae and Semen Armeniacae Amarae has the functions of diffusing the lung and lowering Qi, and the combination of the two is more beneficial to the promotion of lung Qi; the combination of honey-fried Herba Ephedrae and peach kernel can release the lung and moisten the intestines, making the evil Qi disappear from the large intestine;Scutellariabaicalensisis cold and cool, and it can help the monarch and ministerial drugs to warm and dry, so as to reduce phlegm and blood stasis and not to reduce heat and injure Yin. The combination of the above prescription has the function of promoting lung and resolving phlegm, reducing Qi and relieving asthma, promoting blood circulation and removing blood stasis; the combination of the whole formula is compatible, it is based on the persistent roots of asthma and treats both the symptoms and root causes, it can not only be used for the treatment of asthma attack, but also for the remission period of asthma[19-20].

In recent years, studies have found that the innate immune system also plays a certain role in the pathogenesis of childhood asthma, among which the interleukin-17 (IL-17) family members have a close relationship with immune inflammatory response. In the early stage of inflammatory reaction, IL-17 is considered as a promoter, which can not only significantly promote the activation of T cells, but also stimulate epithelial cells, endothelial cells and other factors to produce a variety of factors, so that inflammatory cells can be recruited, causing immune inflammatory damage, especially IL-17A, IL-17E and IL-17F. Studies at home and abroad have found that the expression of IL-17A is significantly increased in the peripheral blood of asthmatic patients, and the elevated degree is positively correlated with the severity of the disease; while IL-17F and IL-17A have high homology and are relatively similar, which can also promote neutrophil infiltration and increase the secretion of mucus, thus aggravating the progress of the disease; and IL-17E is considered to be the most important cytokine in the IL-17 family, which is mainly produced by Th2 cells and mast cells, at the same time, IL-17E can enhance the function of Th2 memory cells, promote the secretion of airway mucus, and participate in the pathogenesis of asthma[21-22]. Eosinophils (EOS) are derived from the proliferation and differentiation of bone marrow CD34+progenitor cells and mainly accumulate in the lungs, their apoptosis is closely related to the occurrence and development of asthma in children, because EOS can not only lead to airway epithelial injury and aggravate mucosal destruction, but also is one of the most important inflammatory cells that cause chronic airway inflammatory response of asthma[23].

In summary, the combination of Acupoint Application of Jiezi Fangxiao Ointment and Pingchuan Prescription has obvious efficacy in the treatment of children with asthma, which can significantly improve the TCM syndrome, airway inflammatory response, lung ventilation function and other indicators in children with high safety and no obvious adverse reactions.