Evidence-Based Complementary and Alternative Medicine

Evidence-Based Complementary and Alternative Medicine / 2020 / Article

Research Article | Open Access

Volume 2020 |Article ID 6760436 | https://doi.org/10.1155/2020/6760436

Ting Yuan, Jun Xiong, Jun Yang, Xue Wang, Yunfeng Jiang, Xiaohong Zhou, Kai Liao, Lingling Xu, "The Effectiveness and Safety of Thunder Fire Moxibustion for Treating Allergic Rhinitis: A PRISMA Compliant Systematic Review and Meta-Analysis", Evidence-Based Complementary and Alternative Medicine, vol. 2020, Article ID 6760436, 13 pages, 2020. https://doi.org/10.1155/2020/6760436

The Effectiveness and Safety of Thunder Fire Moxibustion for Treating Allergic Rhinitis: A PRISMA Compliant Systematic Review and Meta-Analysis

Academic Editor: Deborah A. Kennedy
Received13 Jul 2020
Revised16 Aug 2020
Accepted09 Sep 2020
Published24 Sep 2020

Abstract

Background. Allergic rhinitis (AR) is a noninfectious inflammatory disease caused by allergic individuals exposed to allergens. Western medicine therapy for treating AR causes obvious adverse events, while thunder fire moxibustion (TFM) is known as a safe and effective treatment for AR. Therefore, we conducted this meta-analysis to evaluate the effectiveness and safety of TFM for treating AR. Methods. PubMed, Web of Science, Embase, the Cochrane Library, CNKI, WanFang, VIP, and CBM from inception to April 5, 2020, were searched without any language restriction. Reviewers identified studies, extracted data, and assessed the quality, independently. The primary outcomes were the total effective rate and the TNSS. The secondary outcomes included TNNSS, RQLQ, VAS, serum IgE, IgA, or IgG level, and adverse events. Randomized controlled trials (RCTs) were collected; methodological quality was evaluated using the Cochrane risk of bias assessment tool (RoB), and the level of evidence was rated using the GRADE approach. Meta-analysis was performed using the RevMan5.3.0 software. Results. A total of 18 RCTs were included, including 1600 patients. The results of this meta-analysis showed a statistically significant effect in a total effective rate of T = TFM (RR = 1.07; 95% CI [1.03, 1.12]; ; I2 = 0%) and T = TFM + other treatments (RR = 1.18; 95% CI [1.11, 1.25]; ; I2 = 53%). In addition, TFM intervention also showed significant difference in total symptom score (T = TFM + other treatments) (MD = −1.42; 95% CI [−1.55, −1.29]; ; I2 = 60%) in patients with AR. Conclusion. Existing evidence shows that TFM is safe and effective for AR. Due to the universal low quality of the eligible trials and low evidence level, we should draw our conclusions with caution. Therefore, clinical researchers should carry out more large-sample, multicentre, high-quality randomized controlled clinical trials in the future to verify the clinical efficacy of TFM in treating AR.

1. Introduction

Allergic rhinitis (AR) is a serious global health problem affecting people of all ages in most countries of the world. It is a chronic nasal inflammation caused by exposure of allergic individuals to allergens and can occur within minutes of exposure [1]. Among the allergens of AR, those who are allergic to cold air, pollen, dust and mites are more common. Its main pathological feature is allergen-specific immunoglobulin E (IgE), which binds to the IgE receptors on mast cells and basophils, releases chemical mediators such as histamine, leukotrienes, and cytokines, and acts on nasal mucosa that can lead to the development of allergic rhinitis symptoms [2]. Hyperfunction of T-helper-type 2 mucosal cells accelerates the process of AR [3]. The main symptoms of AR include paroxysmal sneezing, watery nose, nasal itching, and nasal blockage. Besides, some patients also have ocular symptoms, such as itchy eyes, red eyes, and tears [4]. The clinical diagnosis of AR is based on detailed medical history, symptoms, signs, positive skin prick test (SPT), and specific serum IgE levels. At the same time, AR can be classified as light, medium, or severe grades according to its severity [5]. The severity and recurrence of allergic rhinitis seriously affect the quality of life of the patients, including the decrease in working and learning ability and the disorders of sleep and mood [6]. In recent years, the incidence of AR has been on a sharp rise, currently affecting about 10–20% of the population worldwide [7]. Epidemiological surveys show that the prevalence of AR varies from country to country around the world. In American adults, the prevalence of AR ranges from 10 to 30% [8, 9]; in Peru, the overall prevalence of allergic rhinitis was 18%; and in the mainland of China, the prevalence of AR is 4–38% [10].

Currently, the treatment methods for AR are mainly western medicines [11]. Among them, commonly used western medicines include loratadine tablets and inhaled budesonide, and so on [12]. However, the medicines have significant side effects, such as drowsiness, dryness of mouth and nose, and epistaxis. Therefore, the medicines should not be taken for a long time [13].

Thunder fire moxibustion (TFM) is a traditional Chinese medicine (TCM) treatment. It is made of moxa sticks with traditional Chinese medicine powder and moxa wool. It is like a big firecracker. After lighting, ten layers of cotton paper were placed on the acupuncture points to press and warm moxibustion. It produces heat to stimulate specific acupuncture points or parts of the body surface, regulates the function of visceral organs by stimulating meridian qi with the help of thermal radiation, and improves the circulation by penetrating deep tissue through heat [14].

Although several clinical trials have been conducted on TFM for treating AR, no systematic review and meta-analysis of TFM or TFM combined with other treatments for treating AR are yet reported. Intriguingly, many high-quality clinical trials have reported that western medicine has severe adverse reactions, and long-term use is prone to drug resistance. Still, TFM has fewer adverse reactions and higher safety. Hence, the goal of this study was to evaluate the quality of these RCTs to assess the effectiveness and safety of TFM in treating AR and guide clinicians better.

2. Methods

2.1. Protocol and Registration

We conducted a systematic review and meta-analysis in strict accordance with PRISMA (The Preferred Reporting Items for Systematic Review and Meta-analysis) statement [15]. The PRISMA checklist was presented in an online supplementary appendix 1. The protocol was beforehand registered in PROSPERO 2019 CRD42019141113. And it could be found from http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019141113.

2.2. Inclusion Criteria
2.2.1. Types of Studies

All relevant randomized controlled trials (RCTs) or quasi-RCTs of TFM for AR were collected.

2.2.2. Participants

Participants diagnosed with AR according to the allergic rhinitis and its impact on asthma (ARIA) [16] were included. No limitation was set on the patients’ age, gender, occupation, ethnic group, disease duration, syndrome type, source of cases, or disease severity.

2.2.3. Types of Interventions and Comparators

For the trial group, TFM alone or TFM combined with other positive interventions (e.g., western medicine and conventional therapy) were eligible. Excluded therapies were the RCTs of TFM not as a primary therapy. For the control group, positive comparators (e.g., western medicine and conventional therapy), no treatment, and placebo or sham TFM were eligible.

2.2.4. Types of Outcome Measures

Primary outcomes were the total effective rate and the total nasal symptom score (TNSS) [17], which was recorded from a validated daily or weekly diaries or visual analog scale (VAS). The TNSS consisted of four nasal symptoms (rhinorrhea, nasal itching, nasal obstruction, and sneezing) using a five-point scale from 0 to 4 (0 = no symptom, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe). The TNSS was obtained from the sum of all four individual symptom scores, with a total possible score ranging from 0 (no symptoms) to 16 (maximum symptom intensity). Secondary outcomes of interest were presented as follows: (1) total nonnasal symptom score (TNNSS) [17]; (2) rhinitis quality of life questionnaire (RQLQ) [18]; (3) VAS (visual analog scale); (4) laboratory indicators: serum IgE, IgA, or IgG levels; and (5) adverse events.

2.3. Electronic Search Methods

PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang, VIP, and CBM from the inception to April 5, 2020, were searched without any language restriction, but involving only the human subjects. The main keywords included “thunder fire moxibustion,” “allergic rhinitis,” and “RCT.” Also, the searches were rerun before the final analysis that followed the PRISMA checklist. Besides, the grey literature and the references of all included literatures were retrieved manually. The full-search strategy for PubMed is shown in Table 1.


SearchQuery

#1“Allergic rhinitis” [Ti/Ab] or “rhinallergosis” [Ti/Ab] or “hypersensitive rhinitis”
[Ti/Ab] or “anaphylactic rhinitis” [Ti/Ab] or “perennial rhinitis” [Ti/Ab] or “pollinosis” [Ti/Ab] or “seasonal allergic rhinitis” [Ti/Ab] or “nasal allergy” [Ti/Ab]
#2“Thunder fire moxibustion” [Ti/Ab] or “thunder-fire needle” [Ti/Ab] or “thunder fire God moxibustion” [Ti/Ab]
#3“Randomized controlled trial” [Ti/Ab] or “clinical trial” [Ti/Ab] or “randomized” [Ti/Ab]
#4“Allergic rhinitis” [MeSH] or “Rhinitis, Allergic, Seasonal” [Mesh]
#5“Moxibustion” [MeSH]
#6“Randomized controlled trial” [MeSH] or “controlled clinical trial” [MeSH]
#7#1 OR #4
#8#2 OR #5
#9#3 OR #6
#10#7 AND #8 AND #9

2.4. Selection Process

Three independent researchers (TY, WX, and JY) selected qualified literature strictly according to Cochrane Collaborative System Evaluator’s Handbook 5.2.0. [19]. Disagreement was resolved by a tripartite discussion or the fourth researcher (JX).

2.5. Data Extraction and Management

Based on the PICOS principle, we set up the standard data extraction table in advance. Before the formal data extraction, preextraction was conducted twice to ensure the smooth progress of the formal extraction. Data extraction was carried out independently by three researchers (TY, WX, and JY) and cross-checked repeatedly. Disagreement was resolved by a tripartite discussion or the fourth researcher (JX). Meanwhile, the intention-to-treat (ITT) analysis was applied to the missing data. Excel 2007 was used for data extraction. Relevant contents of data extraction included title, author, publication time, average age, sample size, disease type, course of treatment, intervention measures, control measures, adverse reactions, and outcome indicators. When essential data in the literature was missing or incomplete, the study author was contacted by phone or e-mail.

2.6. Assessment of the Methodological Quality

We evaluated the methodological quality of qualified RCTs using the Cochrane risk assessment tool [20] according to Cochrane Reviewer’s Handbook 5.0. It contains seven items: random sequence generation, allocation concealment, blinding of participants or doctors, blinding of outcome evaluator, incomplete outcome data, selective outcome reporting, and other biases. High (H), low (L), and unclear (U) were used to evaluate the degree of risk of bias in each item. Three reviewers (TY, WX, and JY) cross-checked the evaluation results of the included study, respectively. Disagreement was resolved by a tripartite discussion or the fourth researcher (JX).

2.7. Data Synthesis and Analysis

Meta-analysis was performed using RevMan5.3.0 software. The data were summarized using risk ratios (RRs) with 95% CI for binary outcomes or mean difference (MD) with 95% CI for continuous outcomes. Chi-square test and I2 value were used to test the degree of heterogeneity. When , I2 > 50%, no heterogeneity was considered among the trials, and the fixed effect model was used for statistical analysis; otherwise, the random effect model was used. When the clinical heterogeneity between the two studies was substantial, only descriptive analysis was performed. The potential publication bias was tested by using an inverted funnel chart developed by Egger when the number of qualified RCTs was more than 10 [21]. Also, we conducted subgroup analysis and sensitivity analysis to explore the source of heterogeneity.

2.8. Level of Evidence

We selected the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate the level of evidence quality [22]. RCTs started with high level of evidence. We lowered the level of evidence (high, moderate, low, and very low) gradually from the five aspects, including risk of bias, inconsistency, imprecision, indirectness, and publication bias.

3. Results

3.1. Search Results

Three hundred eighty-six literatures were initially retrieved: 20 from PubMed, 24 from Web of Science, 36 from Embase, 11 from Cochrane Library, 63 from CNKI, 49 from WanFang, 48 from VIP, and 135 from CBM. NoteExpress 3.0 software was used to classify and screen the initial study and eliminate the reviews that did not meet the inclusion criteria. Finally, a total of 18 RCTs were included (Figure 1).

3.2. Study Characteristics

Record all characteristics of the included trials. All the studies were published between 2005 and 2019. There were 856 cases in the treatment group and 854 cases in the control group. There were six trials, including three control groups, but only two of them met the criteria. So we only extracted baseline data for these two groups. The number of patients in each clinical study ranged from 22 to 103. Most patients were recruited from the outpatient or inpatient departments. Besides, the result data and other information for each included study were presented in Table 2.


Study IDSample size T/CAgeInterventionPeriod (w)Adverse eventsOutcomeDrop outMoxibustion acupoint
Trial groupControl group

Wang [23]60 (30/30)T: 32.87 ± 11.10
C: 32.80 ± 10.61
TFMMometasone furoate nasal spray3/3NonTotal effective rate, VAS, RQLQ, symptom scoreNonDU23, DU25, DU29, LI20, LU7, LI4, BL1
Zhao et al. [24]102 (51/51)T: 45.33 ± 1.39
C: 45.29 ± 1.35
TFMBudesonide nasal spray3/3NRTotal effective rateNonDU23, DU25, DU29, LI20, LU7, LI4
Zhang [25]60 (30/30)T: 24.72 ± 7.43
C: 25.10 ± 8.14
TFMFlixonase aqueous nasal spray4/4NRTotal effective rateNonDU23, DU25, DU29, LI20, LI4, EX-HN8, BL12, DU14, BL13
Chen [26]206 (103/103)T: 8–55
C: 10–52
TFMOxymetazoline3/3NRTotal effective rateNonDU23, DU25, DU29, LI20, LU7, LI4, BL1
Zhao and Zhang [27]120 (60/60)T: 8–63
C: 12–64
TFMBeclomethasone dipropionate aerosol nasal spray3/3NRTotal effective rateNonDU23, DU25, DU29, LI20, BL1
Zhao et al. [28]110 (55/55)T/C: 47.1 ± 16.6 (11–80)TFMBeclomethasone dipropionate aerosol nasal spray3/3NRTotal effective rate, symptom scoreNonDU23, DU25, DU29, LI20, BL1
Xue et al. [29]60 (30/30)T/C: 32.12 ± 9.69 (18–55)TFMNo treatment3/3NRIgE, IgGNonDU23, DU29, LI20, LI4
Sun [30]60 (30/30)T/C: 12–58TFM + budesonide nasal sprayBudesonide nasal spray3/3NRTotal effective rateNonDU23, DU25, DU29, LI20, BL1
Wu and Zhou [31]200 (100/100)T/C: 10–70TFM + TCMTCM3/3NRTotal effective rateNon
Huang et al. [32]58 (30/28)T: 19.76 ± 1.76 (18–25)
C: 19.62 ± 1.36 (18–23)
TFM + tuinaTuina3/3NRSymptom scoreT: 0
C: 2
DU14, BL13, BL43, BL20, BL23
Zhang [33]130 (65/65)T: 35.69 ± 21.92
C: 34.62 ± 23.57
TFM + acupunctureAcupuncture3/3NRTotal effective rate, symptom scoreNonDU29, LI20, LI4, RN12, RN4, RN6
Yang [34]120 (60/60)T/C: 37.3 ± 7.3 (10–51)TFM + acupunctureAcupuncture3/3NRTotal effective rate, symptom scoreNonDU23, DU25, DU29, LI20, BL1, LI4, BL13
Zhan [35]60 (30/30)T: 9.3 ± 6.1
C: 9.1 ± 5.9
TFM + acupoint patchingAcupoint patching2/2NRTotal effective rate, symptom scoreNonDU23, DU25, DU29, LI20, LI4
Wang [36]60 (30/30)T: 46.25 ± 7.13 (15–68)
C: 46.02 ± 7.11 (15–67)
TFM + acupunctureAcupuncture2/2NRTotal effective rateNonDU29, LI20, LI4, EX-HN8
Ding and Chang [37]48 (24/24)T: 29.1 ± 3.8 (9–49)
C: 27.8 ± 4.1 (8–46)
TFM + acupunctureAcupuncture4/4NRTotal effective rate, symptom scoreNonDU23, DU25, DU29, BL1, LU7, LI20, LI4
Liu et al. [38]44 (22/22)NRTFM + acupunctureAcupuncture4/4NRTotal effective rate, symptom scoreNonDU23, DU25, DU29, BL1, LU7, LI20, LI4
Lu [39]48 (24/24)T: 45.9 ± 12.4 (17–60)
C: 47.8 ± 13.1 (16–62)
TFM + acupunctureAcupuncture4/4NRSymptom scoreNonDU23, DU25, DU29, BL1, LU7, LI20, LI4
Zhang [40]54 (27/27)T: 15–68
C: 16–
66
TFM + acupunctureAcupuncture2/2NRTotal effective rateNonDU29, LI20, LI4, EX-HN8

Note. TFM = thunder fire moxibustion; TCM = traditional Chinese medicine; NR = not reported; VAS = visual analog scale.
3.2.1. Types of Studies

The eligible studies included 14 randomized controlled trials (RCTs) and 4 quasirandomized controlled trials (quasi-RCTs).

3.2.2. Types of Intervention

7 RCTs [2329] adopted TFM treatment alone, 1 RCT [30] adopted TFM + budesonide nasal spray treatment, 1 RCT [31] adopted TFM + TCM treatment, 1 RCT [32] adopted TFM + tuina treatment, 1 RCT [35] adopted TFM + acupoint patching treatment, and 7 RCTs [33, 34, 3640] adopted TFM + acupuncture treatment.

3.2.3. Types of Control

7 RCTs [2328, 30] adopted western medicine treatment, 1 RCT [29] adopted no treatment, 1 RCT [31] adopted traditional Chinese medicine treatment, and 9 RCTs [3240] adopted acupuncture and moxibustion treatment.

3.2.4. Types of Outcome Measures

15 RCTs [2328, 30, 31, 3338, 40] assessed the total effective rate, 9 RCTs [23, 28, 3235, 3739] selected symptom score, 1 RCT [23] assessed VAS score, 1 RCT [23] assessed RQLQ, and 1 RCT [29] assessed the serum of IgE and IgG levels, respectively.

3.3. Risk of Bias Assessment

(1) Randomization: 2 RCTs [23, 31] were randomized by random number table, 2 RCTs [24, 36] were randomized by draw, 1 RCT [25] was randomized by computer, 2 RCTs [34, 35] were randomized by odd-even order, 2 RCTs [38, 40] were randomized by registration order, and 9 RCTs [2630, 32, 33, 37, 39] were randomized word only; (2) allocation hiding: only 1 RCT [25] mentioned proper allocation hiding, and the remaining 17 RCTs did not mention whether allocation hiding; (3) blind method: none of the trials mentioned the blind method; (4) selective report: all studies reported preset outcome indicators; and (5) follow-up and abscission: only 1 RCT [32] did not report the causes of cases of abscission in detail, so rated as high risk, as shown in Table 3 and Figures 2 and 3.


StudyRandom sequence generationAllocation concealmentBlindingOutcome data integritySelective outcome reportingOther biases
Patient/doctor blindingOutcome assessor blinding

Wang [23]Random number tableUncertainUncertainUncertainLow riskLow riskUncertain
Zhao et al. [24]Draw randomUncertainUncertainUncertainLow riskLow riskUncertain
Zhang [25]Computer randomLow riskUncertainUncertainLow riskLow riskUncertain
Chen [26]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Zhao and Zhang [27]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Zhao et al. [28]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Xue et al. [29]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Sun [30]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Wu and Zhou [31]Random number tableUncertainUncertainUncertainLow riskLow riskUncertain
Huang et al. [32]Random wordUncertainUncertainUncertainHigh riskLow riskUncertain
Zhang [33]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Yang [34]Random by odd-even orderUncertainUncertainUncertainLow riskLow riskUncertain
Zhan [35]Random by odd-even orderUncertainUncertainUncertainLow riskLow riskUncertain
Wang [36]Draw randomUncertainUncertainUncertainLow riskLow riskUncertain
Ding and Chang [37]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Liu et al. [38]Random by registration orderUncertainUncertainUncertainLow riskLow riskUncertain
Lu [39]Random wordUncertainUncertainUncertainLow riskLow riskUncertain
Zhang [40]Random by registration orderUncertainUncertainUncertainLow riskLow riskUncertain

3.4. Outcomes
3.4.1. Total Effective Rate

The total effective rate was reported in 15 [2328, 30, 31, 3338, 40] out of 18 studies. The total effective rate of trial group = TFM was reported in 6 studies [2328] and that of trial group = TFM + other treatments was reported in 9 studies [30, 31, 3338, 40]. The total effective rate (trial group = TFM) had statistical significance (RR = 1.07; 95% CI [1.03, 1.12]; ; I2 = 0%) with low or no heterogeneity (Figure 4). The total effective rate (trial group = TFM + other treatments) had statistical significance (RR = 1.18; 95% CI [1.11, 1.25]; P = 0.03; I2 = 53%) with higher heterogeneity (Figure 5). The result showed that TFM had a better effect compared with the control group.

3.4.2. Total Symptom Score

The total symptom score was reported in 9 [23, 28, 3235, 3739] out of 18 studies. Since two studies [23, 32] described only a single symptom integral and did not count the total symptom score, only 7 studies were included for meta-analysis. The total symptom score of trial group = TFM was reported in one study [28], and that of trial group = TFM + other treatments was reported in 6 studies [3335, 3739]. Only 1 RCT [28] was included in trial group = TFM, so descriptive analysis was conducted. And the results showed that the TFM had a significant effect on the clinical symptoms of AR patients, and it was better than the control group. The total symptom score (trial group = TFM + other treatments) had statistical significance (SMD = −1.42; 95% CI [−1.55, −1.29]; ; I2 = 60%) with higher heterogeneity (Figure 6). The result showed that TFM had a better effect compared with the control group.

3.4.3. VAS Score

Only 1 RCT [23] was included, so descriptive analysis was conducted. And the results showed that the comparison of VAS scores between the two groups was statistically significant (). VAS score of the TFM group after treatment was lower than that of the western medicine group, indicating that, after treatment, VAS score of the TFM group could be reduced. Still, the change range was lower than that of the western medicine group.

3.4.4. Rhinitis Quality of Life Questionnaire (RQLQ)

Only 1 RCT [23] was included, so descriptive analysis was conducted. And the results showed that the difference of RQLQ score between the TFM group and the western medicine group was statistically significant (). The RQLQ score of the TFM group after treatment was lower than that of the western medicine group, indicating that, after treatment, the TFM group could reduce the RQLQ score, but the reduction was lower than that of the western medicine group.

3.4.5. Serum IgE and IgG Levels

Only 1 RCT [29] was included, so descriptive analysis was conducted. And the results showed that, compared with the blank control group, , indicating that no statistically significant difference in serum IgG between the healthy population and allergic rhinitis patients; , indicating that serum IgE was statistically significant between the healthy population and allergic rhinitis patients.

3.4.6. Adverse Events

Of 19 trials, only 1 trial [23] reported on adverse events, which reported that no adverse events occurred. No adverse events were reported in the remaining 18 trials.

3.4.7. TFM Performed for AR

We also analyzed the selection of acupoints for the included RCTs. A total of 17 acupoints were selected from 18 studies. Two studies [23, 26, 36, 40] selected the same acupoint therapy, respectively, and three other studies [27, 28, 30, 3739] selected another same acupoint therapy, respectively, but the remaining studies were different. DU29/LI20 (16 studies [2330, 3340], 88.9%) had the highest frequency of use, followed by DU23/LI4 (13 studies [2330, 3340], 72.2%), DU25 (12 studies [2328, 30, 34, 35, 3739], 66.7%), BL1 (9 studies [23, 2628, 30, 34, 3739], 50.0%), LU7 (6 studies [23, 24, 26, 3739], 33.3%), and BL13/EX-HN8 (3 studies [25, 32, 34, 36, 40], 16.7%).The other acupoints were used only one time, as shown in Table 4.


OrderAcupointsFrequency (%, N = 18)

1DU29/LI2016 (88.9%)
2DU23/LI413 (72.2%)
3DU2512 (66.7%)
4BL19 (50.0%)
5LU76 (33.3%)
6BL13/EX-HN83 (16.7%)
7DU142 (11.1%)
8BL12/BL43/BL2/BL23/RN12/RN4/RN61 (0.06%)

3.4.8. Publication Bias

Based on the total effective rate (trial group = TFM) of STATA 12.0 software, we analyzed publication bias through Egger’s test, and the results showed that  = 0.267 > 0.05, and the 95% CI [−1.201, 3.285] contained 0, suggesting that the possibility of publication bias was small. Based on the total effective rate (trial group = TFM + other treatments), the results showed that  = 0.027 < 0.05, and the 95% CI [0.63, 7.86] did not contain 0, suggesting that the possibility of publication bias was bigger, as shown in Figures 7 and 8.

3.4.9. Subgroup Analyses

Because there was no enough data, we did not conduct a subgroup analysis for different groups.

3.4.10. Sensitivity Analysis

Sensitivity analysis was used to evaluate the stability of meta-analysis. We performed a sensitivity analysis by using STATA 12.0 software, such as the effective rate. Sensitivity analysis showed that the results of the effective rate were not stable. We found that the results of heterogeneity comparing the effective rate were significantly reduced (RR = 1.19, 95% CI = 1.12 to 1.27, , I2 = 33.4%) by omitting the study by Ding conducted in 2016 [37]. Therefore, this study [37] was considered as the source of heterogeneity, as shown in Figures 9 and 10.

3.5. Level of Evidence

The results of GRADE analysis showed that the evidence quality of all outcome indicators was low or very low, which was not conducive to our recommendation of the results. We reduced the levels mainly by the risk of bias, inconsistency, and imprecision, as shown in Table 5.


Variable (study number)Sample size (T/C)I 2 value (%)P valueRisk of biasInconsistencyIndirectnessImprecisionPublication biasEffect (95% CI)Level of evidence

Total effective rate (T = TFM) (6)359/35900.046Serious①NonNonSerious③NonRR = 1.07, 95% CI = [1.03, 1.12]Low⊕⊕○○
Total effective rate(T = TFM + other treatments) (9)366/36653.30.029Serious①Serious②NonSerious③Serious④RR = 1.18, 95% CI = [1.11, 1.25]Very low⊕○○○
Total symptom score (9)225/22559.40.031Serious①Serious②NonSerious③NonRR = 1.20, 95% CI = [1.16, 1.23]Very low⊕○○○

T: treatment group; C: control group. ①Blind method is missing, allocation hidden report is insufficient, and random method description is not clear; ②statistical heterogeneity and clinical heterogeneity were more significant; ③the total sample size was small, and OIS was not satisfied (optimal information size); ④Egger’s test showed that , and the 95% CI [0.63, 7.86] did not contain 0, suggesting that the possibility of publication bias was bigger. ⊕⊕○○ represents the low level of evidence. ⊕○○○ represents the very low level of evidence.

4. Discussion

4.1. Main Findings of TFM Intervention Effects

The results of this meta-analysis showed a statistically significant effect in total effective rate of trial group = TFM (RR = 1.07; 95% CI [1.03, 1.12]; P = 0.45; I2 = 0%) and trial group = TFM + other treatments (RR = 1.18; 95% CI [1.11, 1.25]; ; I2 = 53%). In addition, TFM intervention also showed significant differences in the total symptom score (trial group = TFM + other treatments) (MD = −1.42; 95% CI [−1.55, −1.29]; ; I2 = 60%) in patients with AR. Although the preset outcome indicators of VAS score, RQLQ score, and serum IgE and IgG levels were included in this study, only one RCT was included, and then, only descriptive analysis was conducted. And the results showed that the score of the treatment group was lower than the control group. Besides, TFM intervention has fewer adverse reactions. Therefore, TFM treatment for AR is safe and effective, worthy of clinical application.

4.2. Quality and Level of Evidence

The Cochrane risk of bias assessment showed that the quality of evidence in this study varied from low to moderate. Among them, only 1 case was of medium quality, and the remaining 17 cases were of low quality. So the quality of the included RCTs was generally low. Inappropriate random method, allocation concealment, and a lack of blinding of all studies exaggerated the results of the outcome measures. In this review, only 27.78% of the studies and 5.56% of the studies reported correct randomization and allocation of concealment, respectively, which can result in overestimation. Due to the low level of evidence, we recommended TFM to treat AR finitely.

4.3. Discussion of Heterogeneity

The total effective rate of TFM for treating AR showed apparent heterogeneity. To find the source of heterogeneity, we conducted sensitive analysis and found that, after excluding the study by Ding conducted in 2016 [37], the results of heterogeneity comparing the effective rate was obviously reduced (RR = 1.19, 95% CI = 1.12 to 1.27, , I2 = 33.4%). To trace its causes, we found that it had problems of low quality and small sample size. This suggests that the results of this meta-analysis were to some extent influenced by the risk of bias.

4.4. Limitations and Advantages

The present study presented several limitations, as follows.

Firstly, although we collected the abundant literature without any language restriction through a comprehensive searching strategy of nine different databases, we could not be sure that all relevant RCTs were included.

Secondly, limited by the retrieval conditions, only the Chinese and English databases were searched, rendering some language biases. All included studies were published in Chinese and none in English, which restricts the generalizability of the findings due to the context in terms of tradition and culture.

Thirdly, the methodological quality of most eligible trials was low, and there was a severe risk of bias, which reduced the authenticity and reliability of TFM evidence for AR in this study. Although the “random word” was used in 14 of the 18 studies, only 5 correctly described the random method. At the same time, almost all eligible studies did not implement allocation concealment and blind method, which may result in severe implementation of bias and selective bias.

Finally, most of the meta-analysis in this review showed high heterogeneity. And due to the small number of studies included in some outcome indicators and the lack of data in some studies, the subgroup analysis was not carried out according to the preset possible variables.

The study also presented some glaring advantages, as follows.

Most importantly, there are no systematic reviews and meta-analysis of TFM for the treatment of AR. This is the first systematic review designed to evaluate the effectiveness and safety of TFM for AR patients. Finally, we strictly followed the PRISMA guideline for this systematic review and meta-analysis, and the content met the standards. Thus, we speculated that the results of this review could provide evidence on the efficiency and safety of TFM in treating AR, which would benefit the patients and practitioners.

5. Conclusion

This is the first systematic review and meta-analysis designed to assess the effectiveness and safety of TFM for AR patients. And this review included a comprehensive assessment of methodological quality and the level of evidence. Existing evidence shows that TFM is safe and effective in the treatment of AR. Due to the universally low-quality eligible trials and low evidence level, we should draw our conclusions with caution. And clinical researchers should carry out more large-sample, multicentre, high-quality randomized controlled clinical trials in the future to verify the clinical efficacy of TFM in treating AR.

Abbreviations

AR:Allergic rhinitis
TFM:Thunder fire moxibustion
TNSS:Total nasal symptom score
TNNSS:Total nonnasal symptom score
RQLQ:Rhinitis quality of life questionnaire
VAS:Visual analog scale
ARIA:Allergic rhinitis and its impact on asthma
CI:Confidence interval
MD:Mean difference
RR:Risk ratio
RCT:Randomized controlled trial
PRISMA:The Preferred Reporting Items for Systematic Review and Meta-analysis
GRADE:Grading of Recommendations, Assessment, Development and Evaluation.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Authors’ Contributions

JX obtained funds for this study. JX and TY contributed to the conception and design of the study. JX provided methodological advice for the study. JY revised the search strategy. TY, XW, JY, and JX searched, extracted, and analyzed data for studies. FYJ, HXZ, KL, and LLX assisted them. TY wrote the original draft. JX reviewed and edited the manuscript. All authors read and confirmed the final manuscript.

Acknowledgments

This study was supported by the Jiangxi University of Traditional Chinese Medicine 1050 Youth Talent Project (Grant no. 5141900101), Key Research and Development Project of Jiangxi Province (Grant no. 20161BBG70109), Distinguished Young Talents Plan of Jiangxi Province (Grant no. 20171BCB23093), and Natural Science Youth Foundation Key Projects of Jiangxi Province (Grant no. 20192ACB21007).

References

  1. C. P. Andrews, D. Mohar, Y. Salhi, and S. K. Tantry, “Efficacy and safety of twice-daily and once-daily olopatadine-mometasone combination nasal spray for seasonal allergic rhinitis,” Annals of Allergy, Asthma & Immunology, vol. 124, no. 2, pp. 171–178, 2020. View at: Publisher Site | Google Scholar
  2. L. M. Wheatley and A. Togias, “Clinical practice: Allergic rhinitis,” New England Journal of Medicine, vol. 372, no. 25, pp. 456–463, 2015. View at: Publisher Site | Google Scholar
  3. C. Shen, F. Chen, H. Wang, X. Zhang, G. Li, and Z. Wen, “Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels,” Brazilian Journal of Otorhinolaryngology, vol. 86, no. 1, pp. 63–73, 2020. View at: Publisher Site | Google Scholar
  4. J. L. Brożek, J. Bousquet, I. Agache et al., “Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision,” The Journal of Allergy and Clinical Immunology, vol. 140, no. 4, pp. 950–958, 2017. View at: Publisher Site | Google Scholar
  5. J. Montoro, A. Del Cuvillo, J. Mullol et al., “Validation of the modified allergic rhinitis and its impact on asthma (ARIA) severity classification in allergic rhinitis children: the PEDRIAL study,” Allergy, vol. 67, no. 11, pp. 1437–1442, 2012. View at: Publisher Site | Google Scholar
  6. E. O. Meltzer, M. S. Blaiss, R. M. Naclerio et al., “Burden of allergic rhinitis: allergies in America, Latin America, and Asia-Pacific adult surveys,” Allergy Asthma Proc, vol. 33, no. 1, pp. S113–S141, 2012. View at: Publisher Site | Google Scholar
  7. J. L. Brozek, J. Bousquet, and C. E. Baena-Cagnani, “Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision,” Journal of Allergy and Clinical Immunology, vol. 126, no. 3, pp. 466–476, 2000. View at: Google Scholar
  8. J. Bousquet, N. Khalaev, and A. A. Cruz, “Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the world health organization, GA(2)LEN and AllerGen),” Allergy, vol. 63, no. 86, pp. 8–160, 2008. View at: Google Scholar
  9. S. M. Nyenhius and S. K. Mathur, “Rhinitis in older adults,” Current Allergy and Asthma Reports, vol. 13, no. 2, pp. 171–177, 2013. View at: Google Scholar
  10. L. M. Baumann, K. M. Romero, C. L. Robinson et al., “Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization,” Clinical & Experimental Allergy, vol. 45, no. 1, pp. 192–199, 2015. View at: Publisher Site | Google Scholar
  11. J. M. Lehman and M. S. Blaiss, “Pharmacotherapy of allergic rhinitis,” Allergy Frontiers, vol. 5, pp. 19–28, 2010. View at: Google Scholar
  12. A. S. Nickels, V. Dimov, and R. Wolf, “Pharmacokinetic evaluation of olopatadine for the treatment of allergic rhinitis and conjunctivitis,” Expert Opinion on Drug Metabolism & Toxicology, vol. 7, no. 12, pp. 1593–1599, 2011. View at: Publisher Site | Google Scholar
  13. J. Bousquet, R. Lockey, and H. Malling, “Allergen immunotherapy: therapeutic vaccines for allergic diseases A WHO position paper♢,” Journal of Allergy and Clinical Immunology, vol. 102, no. 4, pp. 558–562, 1998. View at: Publisher Site | Google Scholar
  14. World Health Organization and Regional Office for the Western Pacific, WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region, World Health Organization, Geneva, Switzerland, 2007.
  15. D. Moher, A. Liberati, J. Tetzlaff et al., “Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,” BMJ, vol. 339, 2009. View at: Publisher Site | Google Scholar
  16. J. Lin, N. Su, G. Liu et al., “The impact of concomitant allergic rhinitis on asthma control: a cross-sectional nationwide survey in China,” Journal of Asthma, vol. 51, no. 1, pp. 34–43, 2014. View at: Publisher Site | Google Scholar
  17. O. Pfaar, P. Demoly, R. Gerth van Wijk et al., “Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper,” Allergy, vol. 69, no. 7, pp. 854–867, 2014. View at: Publisher Site | Google Scholar
  18. E. F. Juniper, A. K. Thompson, P. J. Ferrie, and J. N. Roberts, “Validation of the standardized version of the rhinoconjunctivitis quality of life Questionnaire,” Journal of Allergy and Clinical Immunology, vol. 104, no. 2, pp. 364–369, 1999. View at: Publisher Site | Google Scholar
  19. Y. Li, L. Cheng, and X. Chen, “Efficacy evaluation of a pollen blocker cream against dust-mite allergy: a multicenter, randomized, double-blind, placebo-controlled crossover trial,” American Journal of Rhinology & Allergy, vol. 29, no. 5, pp. 129–133, 2015. View at: Publisher Site | Google Scholar
  20. A. C. Sterne Jonathan, S. Jelena, and J. Page Matthew, “RoB 2: a revised tool for assessing risk of bias in randomised trials,” BMJ, vol. 366, 2019. View at: Google Scholar
  21. J. P. Vandenbroucke, “Bias in meta-analysis detected by a simple, graphical test. Experts’ views are still needed,” BMJ (Clinical Research ed.), vol. 316, no. 7129, pp. 469–471, 1998. View at: Google Scholar
  22. G. H. Guyatt, A. D. Oxman, G. E. Vist et al., “GRADE: an emerging consensus on rating quality of evidence and strength of recommendations,” BMJ, vol. 336, no. 7650, pp. 924–926, 2008. View at: Publisher Site | Google Scholar
  23. L. Wang, Clinical Study on the Treatment of Allergic Rhinitis with Yang Deficiency by Thunder Fire Moxibustion and the Study on Improving Patients’ Quality of Life, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China, 2019.
  24. C. Q. Zhao, H. Yan, and J. X. Hao, “Clinical effect evaluation of thunder fire moxibustion in the treatment of allergic rhinitis,” Nei Mongol Journal of Traditional Chinese Medicine, vol. 36, no. 7, pp. 61-62, 2017. View at: Google Scholar
  25. Z. X. Zhang, Clinical Study of Lightning Fire Moxibustion in Treating Allergic Rhinitis with Pulmonary Qi Deficiency and Cold, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China, 2015.
  26. L. Y. Chen, “Effect of Zhao’s lightning fire moxibustion and hydroxymezoline on allergic rhinitis,” The Chinese and Foreign Health Abstract, vol. 8, no. 43, pp. 191-192, 2011. View at: Google Scholar
  27. Y. L. Zhao and Li Zhang, “Clinical study on the treatment of perennial allergic rhinitis with ray-fire moxibustion,” Journal of Emergency in Traditional Chinese Medicine, vol. 16, no. 4, p. 422+429, 2007. View at: Google Scholar
  28. S. B. Zhao, Li Zhang, Y. L. Zhao et al., “Clinical study of Zhao Shi’s thunder-fire moxibustion in the treatment of perennial allergic rhinitis,” Journal of Clinical Acupuncture and Moxibustion, vol. 6, pp. 19–21, 2005. View at: Google Scholar
  29. A. G. Xue, G. H. Zhou, J. Q. Li et al., “Clinical control study of modified thunder fire god needle in the treatment of allergic rhinitis,” Shaanxi Journal of Traditional Chinese Medicine, vol. 37, no. 2, pp. 234–236, 2016. View at: Google Scholar
  30. H. Y. Sun, “Thirty cases of allergic rhinitis treated with thunder fire moxibustion combined with rayncott nasal spray,” Clinical Journal of Chinese Medicine, vol. 6, no. 32, pp. 27-28, 2014. View at: Google Scholar
  31. Y. C. Wu and S. J. Zhou, “Clinical observation on the treatment of yang-deficiency allergic rhinitis with ray-fire moxibustion and traditional Chinese medicine in the foot reflex area,” Jiangxi Medicine, vol. 51, no. 5, pp. 458–460, 2016. View at: Google Scholar
  32. C. B. Huang, Q. X. Zhen, Di Tu et al., “Observation on the efficacy of thunder fire god needle combined with massage in the treatment of pulmonary qi deficiency and cold allergic rhinitis,” Chinese Manipulation & Qi Gong Therapy, vol. 10, no. 19, pp. 37–40, 2019. View at: Google Scholar
  33. Z. X. Zhang, “Clinical study of acupuncture combined with thunder fire moxibustion in the treatment of allergic rhinitis,” Systems Medicine and Pharmacology, vol. 3, no. 23, pp. 141–143, 2018. View at: Google Scholar
  34. J. L. Yang, “Clinical study of thunder fire moxibustion combined with acupuncture in the treatment of allergic rhinitis,” The Asia-Pacific Traditional Medicine, vol. 13, no. 10, pp. 109-110, 2017. View at: Google Scholar
  35. J. Zhan, “Observation on therapeutic effect of acupoint application combined with thunder fire moxibustion on children with allergic rhinitis,” Journal of Hubei College of Traditional Chinese Medicine, vol. 19, no. 6, pp. 85–88, 2017. View at: Google Scholar
  36. J. Wang, “Study on the therapeutic effect of acupuncture combined with thunder fire moxibustion on allergic rhinitis,” Journal of Clinical Medical Literature, vol. 3, no. 42, p. 8353, 2016. View at: Google Scholar
  37. Y. N. Ding and X. H. Chang, “Clinical efficacy of three nasal acupuncture combined with thunder-fire moxibustion in the treatment of allergic rhinitis,” Clinical Journal of Chinese Medicine, vol. 8, no. 20, pp. 40-41, 2016. View at: Google Scholar
  38. C. Liu, X. Zhou, and C. H. Wang, “Effect of three nasal acupuncture combined with thunder-fire moxibustion on allergic rhinitis,” Chinese Journal of Gerontology, vol. 35, no. 5, pp. 1196-1197, 2015. View at: Google Scholar
  39. X. P. Lu, “Clinical analysis of the treatment of allergic rhinitis with three nasal needles combined with thunder-fire moxibustion,” Medicine, no. 13, pp. 21-22, 2015. View at: Google Scholar
  40. D. B. Zhang, “Acupuncture combined with thunder fire moxibustion in the treatment of 27 cases of allergic rhinitis,” Shaanxi Journal of Traditional Chinese Medicine, vol. 35, no. 5, pp. 593-594, 2014. View at: Google Scholar

Copyright © 2020 Ting Yuan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder
Views176
Downloads227
Citations

Related articles

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.