# Traditional Chinese Medicine Based Acupoint Application for Asthma Treatment in Children: A Meta-Analysis and Systematic Review

Authors: Yijie Wang; Tingting Guo; Fushuang Yang; Yongjun Li; Lujia Liu; Kexin Lin; Zhijun Li; Youpeng Wang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. By conducting a systematic review of the efficacy of acupoint application on children with asthma. Methods. We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library) for studies from the establishment of the database to October 2021. The included literature studies were randomized control studies investigating the treatment of asthma in children by acupoint application. The primary outcomes included the cure rate, the resolution time of cough, and the resolution time of wheezing. The secondary outcomes included pulmonary function and interleukins. Stata 15 and RevMan 5.4 were used to analyze the extracted data. Results. A total of 24 related studies were included containing 2716 cases. The meta-analysis showed that TCM group was superior to control group in terms of cure rate, pulmonary function (FEV1), and resolution time of wheezing in children with asthma [RR = 1.26,95% (1.21,1.31), P<0.05; SMD = 0.81, 95%CI (0.05,1.56), P<0.05; WMD = −1.40, 95%CI (−1.75, −1.05), P<0.05]. Conclusions. The present study shows that acupoint application is an effective treatment for children with asthma in China, especially in alleviating wheezing and improving quality of life.


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## Body

## 1. Introduction

Asthma is a chronic and refractory disease that affects the quality of human life globally. This chronic inflammation is mainly related to airway hyper-responsiveness and reversible airflow limitation, which causes symptoms such as recurrent wheezing, shortness of breath, chest tightness, and cough [1]. In recent years, the incidence of asthma was increasing year by year. At present, there are about 334 million children with asthma in the world and 30 million children with asthma in China [2, 3]. Respiratory symptoms in children aged 5 to 16 years lack specificity, and they could develop asthma-like symptoms which may be caused by respiratory virus infection or prolonged disease course [4]. This results in overdiagnosis and abuse of adrenal cortical hormones (hormones), which make children and their families bear unnecessary costs and adverse reactions [5]; traditional Chinese medicine has a good clinical effect on children with asthma with low recurrence rate and side effects.Asthma is a refractory disease with high rates of recurrence [6]. Therefore, the treatment principle of this disease in clinical practice basically aims to control the disease progression. Inhaled glucocorticoids, long-actingβ2-receptor agonists (LABA), and leukotriene receptor antagonists are the main controller medications. Short-actingβ2 receptor agonists (SABA) and inhaled anticholinergic drugs are the main relief drugs [7]. Acupoint application of traditional Chinese medicine has a long history. Acupoint application treatment is based on syndrome differentiation and treatment; transdermal drug delivery can avoid the first pass effect of gastrointestinal digestive fluid and the liver and also avoid the “peak-valley phenomenon”. In addition, the interlayer of skin tissue structure has storage capacity, which can make the blood concentration curve of drugs entering human tissues gentle and lasting. Previous studies reported that acupoint application could be used to treat childhood bronchial asthma, and the effective rate could reach 100% [8]. According to the theory of acupoint application, the mechanisms of asthma include acute airway obstruction and inversion of lung Qi which are mainly caused by long-term phlegm retention in the lungs and further aggravated by emotions, diet, fatigue, and physical weakness. Some studies believed that the pathogenesis of childhood bronchial asthma is retaining phlegm, which is directly related with the dysfunction of the liver, spleen, and kidneys. Exogenous lung wind, improper diet, and blockage of chest yang can contribute to asthma [9, 10]. However, the efficacy of acupoint application of traditional Chinese medicine in the treatment of childhood asthma is still unclear. Thus, a meta-analysis was conducted to compare the efficacy of acupoint application in the treatment of childhood asthma.


## 2. Materials and Methods

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and meta-analysis (PRISMA) statement [11]. Scientific databases (PubMed, Embase, Web of Science, Cochrane Library, CBM, CNKI, and Wanfang) were comprehensively searched to identify relevant literature studies without language restriction. Relevant keywords, medical terms, and titles include acupoint application, children, asthma, and randomized controlled trials. The search results included original research papers published in online journals as of October 29, 2021, Specific search method, Supplementary material 1.


### 2.1. Inclusion and Exclusion Criteria

According to the aims of the study, the inclusion criteria were as follows: (1) the included population should meet the diagnostic criteria for asthma, (2) age <15 years old, (3) acupoint application intervention is the main therapeutic approach, (4) randomized controlled trials, and (5) complete original data.Exclusion criteria were as follows: (1) conference abstracts and systematic reviews, (2) repeated publications, (3) animal experiments or nonclinical experiments, (4) articles with unreasonable experimental design, and (5) full text was not available.


### 2.2. Data Extraction

The following data were extracted from each eligible study: first author, country, subjects, number of participants, sex, age, intervention, comparator, treatment stage, treatment duration, follow-up time, lung function, cure rate, the resolution time of wheezing, serum IgE, and other related data. To ensure the quality of the meta-analysis, all eligible articles were independently reviewed and cross-checked by 2 researchers according to standardized methods. If there was any dissent, another reviewer was consulted. A consensus was reached on the selection of the final included studies.


### 2.3. Risk of Bias Assessment

Cochrane risk of bias tool was used to evaluate the risk of bias of each studies containing RCT and the following factors were taken into account: random sequence generation, allocation concealment, blinding of participants and researchers, blinding of outcome assessments, incomplete outcome data, selective reports of outcomes, and other sources of bias. The risk of bias in each aspect was scored as low, high, or unclear risk [12].


### 2.4. Statistical Analysis

Stata/SE12.0 software was used in this meta-analysis. The pooled enumeration data were expressed as relative risk (RR) and 95% confidence interval (CI). The pooled continuous variables were expressed as mean standard deviation (MD) and 95% CI operation.P<0.05 was used as the standard to determine the difference to be statistically significant. Q-test (P-value) and chi-square test (I2) were used to determine the heterogeneity. The heterogeneity was considered not significant if P≥0.1 and I2 ≤ 50%, and the fixed-effects model was used to pool the data. Otherwise, the random-effects model was used to pool the data. The subgroup analysis was used to determine the source of the heterogeneity. Egger’s test was performed to evaluate the publication bias, and P>0.05 indicated that there was no publication bias; otherwise, publication bias existed.


## 2.1. Inclusion and Exclusion Criteria

According to the aims of the study, the inclusion criteria were as follows: (1) the included population should meet the diagnostic criteria for asthma, (2) age <15 years old, (3) acupoint application intervention is the main therapeutic approach, (4) randomized controlled trials, and (5) complete original data.Exclusion criteria were as follows: (1) conference abstracts and systematic reviews, (2) repeated publications, (3) animal experiments or nonclinical experiments, (4) articles with unreasonable experimental design, and (5) full text was not available.


## 2.2. Data Extraction

The following data were extracted from each eligible study: first author, country, subjects, number of participants, sex, age, intervention, comparator, treatment stage, treatment duration, follow-up time, lung function, cure rate, the resolution time of wheezing, serum IgE, and other related data. To ensure the quality of the meta-analysis, all eligible articles were independently reviewed and cross-checked by 2 researchers according to standardized methods. If there was any dissent, another reviewer was consulted. A consensus was reached on the selection of the final included studies.


## 2.3. Risk of Bias Assessment

Cochrane risk of bias tool was used to evaluate the risk of bias of each studies containing RCT and the following factors were taken into account: random sequence generation, allocation concealment, blinding of participants and researchers, blinding of outcome assessments, incomplete outcome data, selective reports of outcomes, and other sources of bias. The risk of bias in each aspect was scored as low, high, or unclear risk [12].


## 2.4. Statistical Analysis

Stata/SE12.0 software was used in this meta-analysis. The pooled enumeration data were expressed as relative risk (RR) and 95% confidence interval (CI). The pooled continuous variables were expressed as mean standard deviation (MD) and 95% CI operation.P<0.05 was used as the standard to determine the difference to be statistically significant. Q-test (P-value) and chi-square test (I2) were used to determine the heterogeneity. The heterogeneity was considered not significant if P≥0.1 and I2 ≤ 50%, and the fixed-effects model was used to pool the data. Otherwise, the random-effects model was used to pool the data. The subgroup analysis was used to determine the source of the heterogeneity. Egger’s test was performed to evaluate the publication bias, and P>0.05 indicated that there was no publication bias; otherwise, publication bias existed.


## 3. Results

### 3.1. Literature Search and Screening

A total of 895 articles were initially retrieved. 563 articles were selected after removing duplicated publication. 464 articles were removed by reading the title and abstract. After reading the full text, 75 articles were removed due to incomplete results, unavailable data, and low quality of the literature, and 24 articles were finally involved in this analysis [13–34] with a total of 2716 patients. The flow chart of literature search is shown in Figure 1.Figure 1
Results of literature screening and the process.


### 3.2. Basic Characteristics and Quality Evaluation of the Included Literature

The 24 literature studies included in this analysis were all randomized controlled studies published in Chinese. A total of 2716 subjects were included, among which 1384 subjects were in the experimental group and 1332 in the control group. The detailed characteristics of the literature are shown in Table1. The plot for risk of bias is shown in Figure 2.Table 1
Basic information of the included literature.
NumberYearAuthorJournalStudy typeCountryInterventionCaseAge(mean ± sd)Gender (male/female)StagePeriod of treatmentFollow-uptimeTreatment groupControl groupTreatment groupControl groupTreatment group (year)Control group (year)Treatment groupControl group12009 [19]Guo JuzhenJournal of Sichuan of Acupoint ApplicationRCTChinaInhalation of pumice aerosol, combined with acupoint application acupoint external application treatmentJust inhale pumice aerosol4032——23/1718/14—30 days3 to 6 months22009 [20]HE WeiChin Pediatr Integr Tradit West MedRCTChinaBased on the treatment of relieving spasmolysis and relieving asthma, intermediate frequency drugs were added to the acupoint for treatmentTreatment of spasmolysis and asthma6060——40/2046/14Attack3 days—32010 [21]HU AieChina Modern DoctorRCTChinaThe aerosol inhalation of Pulmicort in acute episode of asthma and the Chinese herbal acupoint application in its remission period were given to the treatment groupThe aerosol inhalation of Pulmicort in acute episode of asthma was given to the control group50502.41.930/2031/19Duration and remission3 years—42011 [26]SHI DanmeiClinical Journal of Chinese MedicineRCTChinaInhalation budesonide suspension + albuterol atomization solution + inhalation ipratropium bromide atomization, plus Chinese medicine acupoint applicationInhalation budesonide suspension + albuterol atomization solution + ipratropium bromide atomization solution for inhalation treatment154150——73/8167/83-7 days—52010 [25]Shi PinyingJournal of Acupoint ApplicationRCTChinaOn the basis of inhaling seretide for 6 months, Wu’s blistering plaster for acupoint application was applied in dog-daysTreated with seretide inhalation 50μg/100μ40407.9 ± 1.58.2 ± 1.923/1724/16In remission stage6 months—62011 [32]Zhang XiuyingJ. Pediatrics of TCMRCTChinaFu Jiu sticking therapy was administered in combination with beclomethasone dipropionate aerosol or budesonide inhalation powderTreated with beclomethasone dipropionate aerosol or budesonide inhalation powder6060——38/2239/21In remission stage3 years—72012 [15]Deng YupingHubei Journal of TCM AugRCTChinaOn the basis of the treatment with inhalation of seretide powder, the treatment of winter disease in summer was added. On the first day of Tou Fu, Erfu, and Sanfu in summer every year, Sanfu acupoint application of cough and asthma was givenTreatment with inhalation seretide powder was given80807.59 ± 3.317.86 ± 2.9548/3245/35In remission stage1 year—-82012 [24]Luo Jing-yanTianjin Med JRCTChinaAccording to GINA regimen, inhaled glucocorticoid-based stepwise treatment was given, and inhaled budesonide aerosol was selected, on this basis, siji ointment was applied at point 2Inhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalation75516.5 ± 1.36.4 ± 1.443/3227/24Duration6 weeks6 months92012 [25]Luo Jing-yanTianjin Journal of Acupoint ApplicationRCTChinaInhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalationInhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalation56428.74 ± 1.648.61 ± 1.5733/2325/17DurationOnce every 7=10 days, 6 times as a course of treatment6 months102012 [29]Wu FangChina Journal of Chinese Materia MedicaRCTChinaXiaochuangao acupoint paste combined with fluticasone propionate aerosolInhale fluticasone propionate aerosol30307.6 ± 2.47.9 ± 2.515/1516/14In remission stage1 year1 year112015 [34]Zhao JuanClinical Journal of Acupoint ApplicationRCTChinaIn addition to the routine use of glucocorticoid inhalation, observation group (20 cases) dog days into the volt is given selfmade acupoint application paste acupoint stickingUsed conventional glucocorticoid inhalation therapy2020————In remission stage1 year1 year122016 [17]Fang JunmeiRCTChinaOn the basis of inhaling budesonide at less than 5 years old and inhaling sulide at more than 5 years old, combined with point mounting method during the dog and coldest daysYounger than 5 years, inhaled budesonide, older than 5 years, inhaled seretide1601602.5-121.5-1392/6889/71Duration1 year—132017 [18]Gu HongdanChinese Archives of acupoint applicationRCTChinaTreated with Xiao Chuan paste acupoint application combined with fluticasone propionate aerosolInhale fluticasone propionate aerosol50509.73 ± 2.429.65 ± 2.5228/2226/24In remission stage1 year1 year142017 [23]Li GuiyingJournal of Clinic Nursing’s practicalityRCTChinaAlbuterol atomized inhalation combined with magnetic patch (acupoint application therapy) treatmentTreated with aerosol inhalation of salbutamol4040—————30 days—152011 [25]Shen Yi-yunGuiding Journal of Acupoint Application and PharmacologyRCTChinaOn the basis of atomizing inhalation of Pulmicort, Bricanyl, and ipratropium bromide, acupoint sticking therapy with clearing heat stick combined with iontophoresis technology was givenTreated with Pulmicort, Bricanyl, and ipratropium bromide inhalation60606.53 ± 3.346.53 ± 2.0931/2928/32Attack5 days—162017 [28]Shu YifangJournal of Clinical Medicine in PracticeRCTChinaTreated with the combination of budesonide and acupoint application with Chinese herbal medicineTreated with budesonide atomization inhalation40409.1 ± 0.79.5 ± 0.519/2124/16—36 days—172017 [35]Zhou FangChinese Journal of Traditional Medical Science and TechnologyRCTChinaOn the basis of inhaling pumice aerosol, wenyang Qucold paste was applied at summer acupointGive pumice aerosol inhalation4442————In remission stageThree volts a course of treatment—182018 [36]Zhao MeiliGuangxi Journal of Acupoint ApplicationRCTChinaFluticasone propionate aerosol combined with acupoint application treatment, “relieving asthma cough external application powder”Inhale fluticasone propionate aerosol505010.23 ± 2.859.66 ± 2.9325/2520/30In remission stageThe experimental group was treated for 4 weeks as a course of treatment, the control group was treated for 10 days as a course of treatment, and the control group was treated with 4 times of application as a course of treatment—192020 [16]Fan XiaoniContemporary Medical SymposiumRCTChinaSalbutamol combined with acupoint stimulation was used for treatmentTreated with aerosol inhalation of salbutamol40404.57 ± 0.454.85 ± 0.4623/1722/18Attack2 weeks—202020 [33]Zhao BaolingInner Mongolia Med JRCTChinaBudesonide inhalation atomization treatment combined with “winter disease treatment in summer” three Fu stickersTreated with budesonide atomization inhalation49499.33 ± 1.849.19 ± 1.7324/2526/23—36 days—212021 [22]Le LijunJournal of Hubei Polytechnic UniversityRCTChinaTreated with acupoint application combined with budesonide atomization inhalation and symptomatic treatmentTreated with budesonide atomization inhalation48484.74 ± 2.874.34 ± 2.1825/2323/25—A course of treatment was given every week for 2 weeks—222021 [30]Xie JianlingSelfcareRCTChinaOn the basis of drug atomization inhalation treatment, acupoint application of “Shuji Point” was givenTreated with drug atomization inhalation50506.5 ± 3.16.1 ± 3.026/2428/22Duration3 weeks—232021 [31]Yang DongyanPractical Clinical Journal of Integrated Traditional Chinese and Western MedicineRCTChinaRoutine inhalation of budesonide aerosol treatment and Chinese medicine treatment of winter disease summer acupoint applicationTreated with budesonide atomization inhalation38387.28 ± 0.497.30 ± 0.51——In remission stage3 months—242015 [14]Chen YanToday NurseRCTChinaAdd acupoint application on the basis of Singulair or sulfone spraysTreatment was given with Singulair or sulfone sprays5050——27/2324/26In remission stage3 summer—Figure 2
Risk of bias summary and graph.


### 3.3. Meta-Analysis Results

#### 3.3.1. Cure Rate

There were 18 studies [13–17, 19–23, 26, 27, 29–32, 35, 36] mentioning the cure rate of the two groups which was expressed as dichotomous variables. The treatment stage was used for subgroup analysis. The fixed-effects model was employed (I2 = 48.1%, P = 0.012), and the pooled results showed that there was a statistically significant difference between the two groups [RR = 1.26, 95% (1.21, 1.31), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in treating childhood asthma (Figure 3(a)).Figure 3
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on cure rate.
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger’s and Begg’s tests were used to analyze the funnel plot. The results of Egger’s and Begg’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 3(b), 3)(c).


#### 3.3.2. Pulmonary Function (FEV1)

In the included articles, 8 studies [15–17, 22, 24, 28, 29, 33] mentioned FEV1-related indicators, which were presented as continuous variables. The random-effects model (I2 = 96.7%, P = 0) was used to pool the effect size, and the pooled results showed that the difference between the two groups was statistically significant [SMD = 0.81, 95%CI (0.05, 1.56), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving pulmonary function (Figure 4(a)).Figure 4
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on pulmonary function (FEV1).
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger ’s and Begg ’s tests were used to analyze the funnel plot. The results of Egger ’s and Begg ’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 4(b), 4(c)).


### 3.4. Function (FEV1)

#### 3.4.1. The Resolution Time of Wheezing

A total of 4 papers [13,22,28,33] reported the resolution time of wheezing, which was presented as a continuous variable. The random-effects model (I2 = 85.8%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was statistically significant [WMD = −1.40, 95%CI (−1.75, −1.05), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving asthma symptoms in children (Figure 5(a)). Sensitivity analysis showed that there was no significant change in effect size after removing the studies one by one (Figure 5(b)).Figure 5
Forest plot and sensitivity analysis of meta-analysis on the resolution time of wheezing.
(a)(b)


#### 3.4.2. Serum IgE Level

A total of 4 studies [13, 17, 26, 35] reported serum IgE level which was expressed as continuous variables. The random-effects model (I 2 = 99.1%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [SMD = 1.39, 95%CI (−0.65, 3.44), P<0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the IgE level (Figure 6).Figure 6
Forest plot of meta-analysis on serum IgE level.


#### 3.4.3. Occurrence of Asthma

A total of 4 [14, 31, 35, 37] studies reported the occurrence of asthma which were expressed as continuous variables. The random-effects model (I 2 = 98.2%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [ SMD = −0.89, (−2.82, 1.04), P>0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the occurrence of asthma (Figure 7).Figure 7
Forest plot of meta-analysis on the occurrence of asthma.


## 3.1. Literature Search and Screening

A total of 895 articles were initially retrieved. 563 articles were selected after removing duplicated publication. 464 articles were removed by reading the title and abstract. After reading the full text, 75 articles were removed due to incomplete results, unavailable data, and low quality of the literature, and 24 articles were finally involved in this analysis [13–34] with a total of 2716 patients. The flow chart of literature search is shown in Figure 1.Figure 1
Results of literature screening and the process.


## 3.2. Basic Characteristics and Quality Evaluation of the Included Literature

The 24 literature studies included in this analysis were all randomized controlled studies published in Chinese. A total of 2716 subjects were included, among which 1384 subjects were in the experimental group and 1332 in the control group. The detailed characteristics of the literature are shown in Table1. The plot for risk of bias is shown in Figure 2.Table 1
Basic information of the included literature.
NumberYearAuthorJournalStudy typeCountryInterventionCaseAge(mean ± sd)Gender (male/female)StagePeriod of treatmentFollow-uptimeTreatment groupControl groupTreatment groupControl groupTreatment group (year)Control group (year)Treatment groupControl group12009 [19]Guo JuzhenJournal of Sichuan of Acupoint ApplicationRCTChinaInhalation of pumice aerosol, combined with acupoint application acupoint external application treatmentJust inhale pumice aerosol4032——23/1718/14—30 days3 to 6 months22009 [20]HE WeiChin Pediatr Integr Tradit West MedRCTChinaBased on the treatment of relieving spasmolysis and relieving asthma, intermediate frequency drugs were added to the acupoint for treatmentTreatment of spasmolysis and asthma6060——40/2046/14Attack3 days—32010 [21]HU AieChina Modern DoctorRCTChinaThe aerosol inhalation of Pulmicort in acute episode of asthma and the Chinese herbal acupoint application in its remission period were given to the treatment groupThe aerosol inhalation of Pulmicort in acute episode of asthma was given to the control group50502.41.930/2031/19Duration and remission3 years—42011 [26]SHI DanmeiClinical Journal of Chinese MedicineRCTChinaInhalation budesonide suspension + albuterol atomization solution + inhalation ipratropium bromide atomization, plus Chinese medicine acupoint applicationInhalation budesonide suspension + albuterol atomization solution + ipratropium bromide atomization solution for inhalation treatment154150——73/8167/83-7 days—52010 [25]Shi PinyingJournal of Acupoint ApplicationRCTChinaOn the basis of inhaling seretide for 6 months, Wu’s blistering plaster for acupoint application was applied in dog-daysTreated with seretide inhalation 50μg/100μ40407.9 ± 1.58.2 ± 1.923/1724/16In remission stage6 months—62011 [32]Zhang XiuyingJ. Pediatrics of TCMRCTChinaFu Jiu sticking therapy was administered in combination with beclomethasone dipropionate aerosol or budesonide inhalation powderTreated with beclomethasone dipropionate aerosol or budesonide inhalation powder6060——38/2239/21In remission stage3 years—72012 [15]Deng YupingHubei Journal of TCM AugRCTChinaOn the basis of the treatment with inhalation of seretide powder, the treatment of winter disease in summer was added. On the first day of Tou Fu, Erfu, and Sanfu in summer every year, Sanfu acupoint application of cough and asthma was givenTreatment with inhalation seretide powder was given80807.59 ± 3.317.86 ± 2.9548/3245/35In remission stage1 year—-82012 [24]Luo Jing-yanTianjin Med JRCTChinaAccording to GINA regimen, inhaled glucocorticoid-based stepwise treatment was given, and inhaled budesonide aerosol was selected, on this basis, siji ointment was applied at point 2Inhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalation75516.5 ± 1.36.4 ± 1.443/3227/24Duration6 weeks6 months92012 [25]Luo Jing-yanTianjin Journal of Acupoint ApplicationRCTChinaInhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalationInhaled glucocorticoid-based step therapy was administered according to the GINA protocol, using budesonide aerosol inhalation56428.74 ± 1.648.61 ± 1.5733/2325/17DurationOnce every 7=10 days, 6 times as a course of treatment6 months102012 [29]Wu FangChina Journal of Chinese Materia MedicaRCTChinaXiaochuangao acupoint paste combined with fluticasone propionate aerosolInhale fluticasone propionate aerosol30307.6 ± 2.47.9 ± 2.515/1516/14In remission stage1 year1 year112015 [34]Zhao JuanClinical Journal of Acupoint ApplicationRCTChinaIn addition to the routine use of glucocorticoid inhalation, observation group (20 cases) dog days into the volt is given selfmade acupoint application paste acupoint stickingUsed conventional glucocorticoid inhalation therapy2020————In remission stage1 year1 year122016 [17]Fang JunmeiRCTChinaOn the basis of inhaling budesonide at less than 5 years old and inhaling sulide at more than 5 years old, combined with point mounting method during the dog and coldest daysYounger than 5 years, inhaled budesonide, older than 5 years, inhaled seretide1601602.5-121.5-1392/6889/71Duration1 year—132017 [18]Gu HongdanChinese Archives of acupoint applicationRCTChinaTreated with Xiao Chuan paste acupoint application combined with fluticasone propionate aerosolInhale fluticasone propionate aerosol50509.73 ± 2.429.65 ± 2.5228/2226/24In remission stage1 year1 year142017 [23]Li GuiyingJournal of Clinic Nursing’s practicalityRCTChinaAlbuterol atomized inhalation combined with magnetic patch (acupoint application therapy) treatmentTreated with aerosol inhalation of salbutamol4040—————30 days—152011 [25]Shen Yi-yunGuiding Journal of Acupoint Application and PharmacologyRCTChinaOn the basis of atomizing inhalation of Pulmicort, Bricanyl, and ipratropium bromide, acupoint sticking therapy with clearing heat stick combined with iontophoresis technology was givenTreated with Pulmicort, Bricanyl, and ipratropium bromide inhalation60606.53 ± 3.346.53 ± 2.0931/2928/32Attack5 days—162017 [28]Shu YifangJournal of Clinical Medicine in PracticeRCTChinaTreated with the combination of budesonide and acupoint application with Chinese herbal medicineTreated with budesonide atomization inhalation40409.1 ± 0.79.5 ± 0.519/2124/16—36 days—172017 [35]Zhou FangChinese Journal of Traditional Medical Science and TechnologyRCTChinaOn the basis of inhaling pumice aerosol, wenyang Qucold paste was applied at summer acupointGive pumice aerosol inhalation4442————In remission stageThree volts a course of treatment—182018 [36]Zhao MeiliGuangxi Journal of Acupoint ApplicationRCTChinaFluticasone propionate aerosol combined with acupoint application treatment, “relieving asthma cough external application powder”Inhale fluticasone propionate aerosol505010.23 ± 2.859.66 ± 2.9325/2520/30In remission stageThe experimental group was treated for 4 weeks as a course of treatment, the control group was treated for 10 days as a course of treatment, and the control group was treated with 4 times of application as a course of treatment—192020 [16]Fan XiaoniContemporary Medical SymposiumRCTChinaSalbutamol combined with acupoint stimulation was used for treatmentTreated with aerosol inhalation of salbutamol40404.57 ± 0.454.85 ± 0.4623/1722/18Attack2 weeks—202020 [33]Zhao BaolingInner Mongolia Med JRCTChinaBudesonide inhalation atomization treatment combined with “winter disease treatment in summer” three Fu stickersTreated with budesonide atomization inhalation49499.33 ± 1.849.19 ± 1.7324/2526/23—36 days—212021 [22]Le LijunJournal of Hubei Polytechnic UniversityRCTChinaTreated with acupoint application combined with budesonide atomization inhalation and symptomatic treatmentTreated with budesonide atomization inhalation48484.74 ± 2.874.34 ± 2.1825/2323/25—A course of treatment was given every week for 2 weeks—222021 [30]Xie JianlingSelfcareRCTChinaOn the basis of drug atomization inhalation treatment, acupoint application of “Shuji Point” was givenTreated with drug atomization inhalation50506.5 ± 3.16.1 ± 3.026/2428/22Duration3 weeks—232021 [31]Yang DongyanPractical Clinical Journal of Integrated Traditional Chinese and Western MedicineRCTChinaRoutine inhalation of budesonide aerosol treatment and Chinese medicine treatment of winter disease summer acupoint applicationTreated with budesonide atomization inhalation38387.28 ± 0.497.30 ± 0.51——In remission stage3 months—242015 [14]Chen YanToday NurseRCTChinaAdd acupoint application on the basis of Singulair or sulfone spraysTreatment was given with Singulair or sulfone sprays5050——27/2324/26In remission stage3 summer—Figure 2
Risk of bias summary and graph.


## 3.3. Meta-Analysis Results

### 3.3.1. Cure Rate

There were 18 studies [13–17, 19–23, 26, 27, 29–32, 35, 36] mentioning the cure rate of the two groups which was expressed as dichotomous variables. The treatment stage was used for subgroup analysis. The fixed-effects model was employed (I2 = 48.1%, P = 0.012), and the pooled results showed that there was a statistically significant difference between the two groups [RR = 1.26, 95% (1.21, 1.31), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in treating childhood asthma (Figure 3(a)).Figure 3
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on cure rate.
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger’s and Begg’s tests were used to analyze the funnel plot. The results of Egger’s and Begg’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 3(b), 3)(c).


### 3.3.2. Pulmonary Function (FEV1)

In the included articles, 8 studies [15–17, 22, 24, 28, 29, 33] mentioned FEV1-related indicators, which were presented as continuous variables. The random-effects model (I2 = 96.7%, P = 0) was used to pool the effect size, and the pooled results showed that the difference between the two groups was statistically significant [SMD = 0.81, 95%CI (0.05, 1.56), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving pulmonary function (Figure 4(a)).Figure 4
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on pulmonary function (FEV1).
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger ’s and Begg ’s tests were used to analyze the funnel plot. The results of Egger ’s and Begg ’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 4(b), 4(c)).


## 3.3.1. Cure Rate

There were 18 studies [13–17, 19–23, 26, 27, 29–32, 35, 36] mentioning the cure rate of the two groups which was expressed as dichotomous variables. The treatment stage was used for subgroup analysis. The fixed-effects model was employed (I2 = 48.1%, P = 0.012), and the pooled results showed that there was a statistically significant difference between the two groups [RR = 1.26, 95% (1.21, 1.31), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in treating childhood asthma (Figure 3(a)).Figure 3
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on cure rate.
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger’s and Begg’s tests were used to analyze the funnel plot. The results of Egger’s and Begg’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 3(b), 3)(c).


## 3.3.2. Pulmonary Function (FEV1)

In the included articles, 8 studies [15–17, 22, 24, 28, 29, 33] mentioned FEV1-related indicators, which were presented as continuous variables. The random-effects model (I2 = 96.7%, P = 0) was used to pool the effect size, and the pooled results showed that the difference between the two groups was statistically significant [SMD = 0.81, 95%CI (0.05, 1.56), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving pulmonary function (Figure 4(a)).Figure 4
Forest plot, funnel plot, and sensitivity analysis of meta-analysis on pulmonary function (FEV1).
(a)(b)(c)A funnel plot was used to directly visualize publication bias, and Egger ’s and Begg ’s tests were used to analyze the funnel plot. The results of Egger ’s and Begg ’s test showed no significant differenceP<0.05. Additionally, the results of sensitivity analysis showed that after excluding the study one by one, there was no significant change in effect size (Figures 4(b), 4(c)).


## 3.4. Function (FEV1)

### 3.4.1. The Resolution Time of Wheezing

A total of 4 papers [13,22,28,33] reported the resolution time of wheezing, which was presented as a continuous variable. The random-effects model (I2 = 85.8%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was statistically significant [WMD = −1.40, 95%CI (−1.75, −1.05), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving asthma symptoms in children (Figure 5(a)). Sensitivity analysis showed that there was no significant change in effect size after removing the studies one by one (Figure 5(b)).Figure 5
Forest plot and sensitivity analysis of meta-analysis on the resolution time of wheezing.
(a)(b)


### 3.4.2. Serum IgE Level

A total of 4 studies [13, 17, 26, 35] reported serum IgE level which was expressed as continuous variables. The random-effects model (I 2 = 99.1%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [SMD = 1.39, 95%CI (−0.65, 3.44), P<0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the IgE level (Figure 6).Figure 6
Forest plot of meta-analysis on serum IgE level.


### 3.4.3. Occurrence of Asthma

A total of 4 [14, 31, 35, 37] studies reported the occurrence of asthma which were expressed as continuous variables. The random-effects model (I 2 = 98.2%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [ SMD = −0.89, (−2.82, 1.04), P>0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the occurrence of asthma (Figure 7).Figure 7
Forest plot of meta-analysis on the occurrence of asthma.


## 3.4.1. The Resolution Time of Wheezing

A total of 4 papers [13,22,28,33] reported the resolution time of wheezing, which was presented as a continuous variable. The random-effects model (I2 = 85.8%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was statistically significant [WMD = −1.40, 95%CI (−1.75, −1.05), P<0.05]. The meta-analysis results presented that the effect of acupoint application was significantly superior to that of the control group in improving asthma symptoms in children (Figure 5(a)). Sensitivity analysis showed that there was no significant change in effect size after removing the studies one by one (Figure 5(b)).Figure 5
Forest plot and sensitivity analysis of meta-analysis on the resolution time of wheezing.
(a)(b)


## 3.4.2. Serum IgE Level

A total of 4 studies [13, 17, 26, 35] reported serum IgE level which was expressed as continuous variables. The random-effects model (I 2 = 99.1%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [SMD = 1.39, 95%CI (−0.65, 3.44), P<0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the IgE level (Figure 6).Figure 6
Forest plot of meta-analysis on serum IgE level.


## 3.4.3. Occurrence of Asthma

A total of 4 [14, 31, 35, 37] studies reported the occurrence of asthma which were expressed as continuous variables. The random-effects model (I 2 = 98.2%, P = 0) was used to pool the effect size. The pooled results showed that the difference between the two groups was not statistically significant [ SMD = −0.89, (−2.82, 1.04), P>0.05]. The meta-analysis results demonstrated that there was no significant difference between the experimental group and the control group in the occurrence of asthma (Figure 7).Figure 7
Forest plot of meta-analysis on the occurrence of asthma.


## 4. Discussion

With the improvement of medical conditions, increasing attention has been paid to the prevention and treatment of asthma. However, due to air pollution, changes in living and diet habits, and other factors [38], the incidence of childhood asthma has been increased. From the perspective of TCM, asthma belongs to the category of “wheezing disease” as termed by TCM. This concept was first mentioned in the “Huangdi Neijing”. Wheezing disease is recurrent due to the failure in completely removing the etiological factor, subsequently aggravated by repeated exposure to exogenous pathogens [39]. Traditional Chinese medicine classifies asthma as “wind-cough” and “wheezing cough,” and the treatment scheme adopts the principle of syndrome differentiation and treatment, treating both inside and outside. Li Yue Parallel Prose once said, “The reason of external governance is the reason of internal governance. Though it is treated externally, nothing can be treated internally.” External treatment and internal treatment can complement and coordinate each other. Acupoint application has a long history in the external treatment of asthma. It can directly act on specific acupoints of the human body, and its multiple effects such as comprehensive drugs, acupoints, and meridians will direct the efficacy of the disease [39]. Based on the comprehensive analysis of the included literature studies, most of the basic drugs used for acupoint application were Chinese mustard seed, Asarum, Euphorbia kansui, and Rhizoma corydalis. White mustard has the function of warming lung and reducing phlegm. Relevant studies show that the efficacy of white mustard in adhesive can quickly penetrate into the skin and release stably [40]. Asarum pungent and warm, return to the heart, lung, and kidney meridian, has the effect of warming lung and hua Yin, etc. Asarum volatile oil can inhibit the release of inflammatory mediators, reduce histamine content, and fight against histamine or prostaglandin E caused by increased capillary permeability. Euphorbia kansui bitter cold, belongs to the lung, kidney, and spleen meridian, has the effect of purging water by drinking. Rhizoma corydalis tastes hard, warm, goes to the liver and stomach meridian, with qi, pain, blood circulation, and blood stasis [41]. The combination of the four herbs has the effect of relieving phlegm and benefiting qi, warming lung, and relieving cough. Acupoints are applied at the locations of lung acupoints, ding asthma acupoints, spleen deficiency, kidney deficiency, etc. The back acupoints are closely related to the sympathetic nerve. Stimulating acupoints can excite the sympathetic nerve, reduce the vagus nerve tension, and have the effect of relieving spasm and relieving cough [42].The external therapy in acupoint application is an important approach to treat childhood asthma [43]. This therapy is easy to use, simple to operate, and good in compliance, showing a definite and rapid effect. Treatment is mainly based on acupoint application, pediatric massage, acupuncture, nasal drip of acupoint application, and fumigation and washing by using acupoint application. Among them, acupoint application is a common treatment method in pediatrics. Acupoint application can exert multiple effects in the treatment of asthma. The drug can not only be absorbed through the skin but can also promote the relaxation of bronchial smooth muscle, and thus dilate the bronchus and improve the symptoms of airway spasm. Meanwhile, through the special physiological amplification effect of the meridian points, it can exert anti-inflammatory effects, adjust the immune function of the body, improve blood circulation, and regulate the functions of the nerves, body fluids, and endocrine system, etc. Xunbin et al. [44] reported 111 cases and used acupoint application (Baijizi, Corydalis, Asarum, cinnamon, ginger juice, and starch) to conduct acupoint application on the specific points (Shuangfeishu, Shuangxinshu, Shuanggeshu, Shuangzusanli, Shuangfengmen, ShuangjueYinshu, Shuanggeshu, and Shuangpishu points). The results showed that the treatment was remarkably effective in 50 cases, effective in 7 cases, and ineffective in 2 cases, with a total effective rate of 96.1%. Yang Yafeng [45] treated childhood bronchial asthma by acupoint application, and the total effective rate was 92.5% after 1 year. It showed that the adjuvant therapy of acupoint application was also rather important in acute asthma attack. For children treated with Western medicine alone, the effective rate was 84.5%. The effective rate reached 97.9% after a combined use with acupoint application treatment. Acupoint application exerts a satisfactory auxiliary effect on the treatment of childhood bronchial asthma, which improves the clinical efficacy. This method is easy to operate in clinical practice, and it is safe and reliable for children to use without pain.This study had several limitations. First, although we attempted to address heterogeneity through subgroup and sensitivity analyses, the heterogeneity in statistics and clinical data might raise doubts about the validity of this study. The heterogeneity of the study population made it challenging to prove that the results were meaningful. Second, the sample size was small, and the occurrence of asthma was low in many included studies with low quality. Third, the source of the research object is single. Thus, the uncertainty in the analysis was increased. The RCT methods in the included studies were generally poor since most risk items were unclear, especially the allocation concealment, blindness, and selective outcome reporting. This limitation might reduce the credibility of our conclusions.


## 5. Conclusion

The present study shows that acupoint application is an effective treatment for children with asthma in China, especially in alleviating wheezing and improving quality of life. Due to the limitations of the study, further research should be conducted in the future with rigorous design, large sample size, sham/placebo control or blank/waiting control, and accurate report to support the evidence of acupoint application treatment in childhood asthma. Furthermore, since all studies were conducted in China, further studies in other countries are necessary to improve the applicability and generalizability of the results.



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*Source: 7500056-2022-09-26.xml*