# Acupuncture Therapy for Functional Effects and Quality of Life in COPD Patients: A Systematic Review and Meta-Analysis

Authors: Jiajia Wang; Jiansheng Li; Xueqing Yu; Yang Xie
Journal: BioMed Research International
 (2018)

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## Abstract

Objective. This study aimed to evaluate the efficacy and safety of acupuncture therapy (AT) for improving functional effects and quality of life in COPD patients.Methods. PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang Data were searched. The randomized controlled trials (RCTs) evaluating the effect of AT on COPD patients were included. Primary outcome measures included six-minute walk distance (6MWD) and St. George’s Respiratory Questionnaire (SGRQ). Study selection, data extraction, and risk of bias assessment were independently conducted, respectively. Statistical analysis was conducted by RevMan software (version 5.3) and Stata software (version 12.0).Results. Nineteen studies (1298 participants) were included. 6MWD improved more (MD: 47.84; 95% CI: 23.33 to 72.35; Z = 3.83, P=0.0001) and effective rate was higher (OR: 2.26; 95% CI: 1.43 to 3.58; Z = 3.48, P=0.0005) in the experimental group compared to the control group. Symptom domain scores (MD: −24.86; 95% CI: −32.17 to −17.55; Z = 6.66, P<0.00001), activity domain scores (MD: −16.52; 95% CI: −22.57 to −10.47; Z = 5.36, P<0.00001) and impact domain scores (MD: −13.07; 95% CI: −17.23 to −8.92; Z = 6.16, P<0.00001) of SGRQ in the experimental group improved more compared to the control group. There was no significant improvement in SGRQ total scores between two groups. The improvement of FEV1 was not significant between two groups, yet subgroup analysis showed that patients treated with AT adjunctive to other treatments improved more in FEV1 (MD: 0.41; 95% CI: 0.28 to 0.54; Z = 6.01, P<0.00001) compared to those treated with other treatments alone.Conclusion. AT may be effective in improving functional effects and quality of life in COPD patients. Besides, AT may also improve pulmonary function of patients with COPD. However, further high-quality RCTs are needed to confirm the efficacy and safety of AT for COPD patients.


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## Body

## 1. Introduction

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality, is characterized by progressive airflow obstruction, airway inflammation, and systemic effects or comorbidities and is projected to be the third leading cause of death worldwide by 2030 [1, 2]. Since breathlessness, exercise limitation, and health status impairment broadly exist in patients with COPD, effective measures should be taken to improve symptoms, exercise tolerance, and health status based on an individualized assessment of disease [1]. Although appropriate pharmacologic therapy has effect in reducing COPD symptoms and the frequency and severity of exacerbations and improving health status and exercise tolerance [1], its cost and adverse effects can never be ignored.Acupuncture therapy (AT), one of the most popular treatments in alternative medicine, has been proven to be cost-effective and safe in many conditions [3–5]. However, there is limited evidence concerning its efficacy and safety. One previous review showed that AT might result in clinically important improvements in quality of life and dyspnea of COPD patients, but it is outdated [6]. Moreover, the interventions of included studies involved point application therapy, acupressure, and transcutaneous electrical stimulation over acupuncture points (Acu-TENS), and these techniques may not genuinely reflect the efficacy of AT based on theories of traditional Chinese medicine. Therefore, the current review aims to evaluate the efficacy and safety of AT for improving functional effects and quality of life in COPD patients.


## 2. Methods

### 2.1. Inclusion and Exclusion Criteria

We included randomized controlled trials (RCTs) in which the effects of AT on COPD patients were evaluated.Participants had COPD defined as a clinical diagnosis of COPD, with a postbronchodilator fixed ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70 measured by spirometry, and those who had an acute exacerbation within four weeks before the study were excluded.The intervention included AT, such as manual acupuncture, electroacupuncture, auricular acupuncture, and warm acupuncture, yet noninvasive techniques, such as single moxibustion, acupressure, point application, laser acupuncture, or Acu-TENS, were excluded.Primary outcome measures included any of the following: (i) six-minute walk test/distance (6MWT/6MWD) [26] and (ii) St. George’s Respiratory Questionnaire (SGRQ) [27]. Secondary outcome measures included any of the following: (i) FEV1, (ii) modified Medical Research Council dyspnea scale (mMRC) [28], (iii) effective rate, and (iv) adverse effects.


### 2.2. Literature Search

PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang Data were searched from their inception to 31 December 2017. We developed detailed search strategies for each electronic database without language restrictions. Reference lists of eligible studies and previous systematic reviews were also reviewed to identify further eligible studies.


### 2.3. Study Selection

Two review authors (Yang Xie and Xueqing Yu) independently examined titles and abstracts retrieved from the search and selected all potentially eligible studies. Then these full-text articles were obtained and the same review authors reviewed them independently against the inclusion and exclusion criteria. A third review author (Jiansheng Li) acted as an arbiter when consensus could not be reached.


### 2.4. Data Extraction

Data extraction was independently conducted by two review authors (Yang Xie and Xueqing Yu) using a standardized data extraction sheet, involving information of authors, year of publication, study design, participants, intervention, comparator, and outcomes, with a third review author (Jiansheng Li) acting as an arbiter when disagreements existed between Yang Xie and Xueqing Yu.


### 2.5. Assessment of Risk of Bias

Methodological quality was evaluated using the Cochrane tool for assessing risk of bias in RCTs [29]. Two review authors (Yang Xie and Xueqing Yu) independently assessed and scored each study with a third review author (Jiansheng Li) acting as an arbiter when disagreements existed.


### 2.6. Statistical Analysis

Statistical analysis was conducted by RevMan software (version 5.3) [30] and Stata software (version 12.0; StataCorp LP, USA). We summarized data using odds ratio (OR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. If the data could not be combined into a meta-analysis, we summarized them in the text. We used a χ2 test to estimate heterogeneity of both the MD and OR. Further analysis was performed using theI2 test. A random-effect model was used to interpret the results if heterogeneity was statistically significant, whereas a fixed-effect model was used if heterogeneity was not statistically significant. We regarded heterogeneity as substantial whenI2 was greater than 50% or a low P value (P<0.10) was reported for the χ2 test [31]. When more than 10 studies were included in the meta-analysis, we would investigate publication bias by funnel plots. In addition, a metaregression analysis was performed to explore potential associations between effect size and covariates of interest (publication year, region, intervention forms, sample size, and treatment period). If necessary, we conducted subgroup analysis to assess whether the treatment effects were different in different subgroups.


## 2.1. Inclusion and Exclusion Criteria

We included randomized controlled trials (RCTs) in which the effects of AT on COPD patients were evaluated.Participants had COPD defined as a clinical diagnosis of COPD, with a postbronchodilator fixed ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) < 0.70 measured by spirometry, and those who had an acute exacerbation within four weeks before the study were excluded.The intervention included AT, such as manual acupuncture, electroacupuncture, auricular acupuncture, and warm acupuncture, yet noninvasive techniques, such as single moxibustion, acupressure, point application, laser acupuncture, or Acu-TENS, were excluded.Primary outcome measures included any of the following: (i) six-minute walk test/distance (6MWT/6MWD) [26] and (ii) St. George’s Respiratory Questionnaire (SGRQ) [27]. Secondary outcome measures included any of the following: (i) FEV1, (ii) modified Medical Research Council dyspnea scale (mMRC) [28], (iii) effective rate, and (iv) adverse effects.


## 2.2. Literature Search

PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang Data were searched from their inception to 31 December 2017. We developed detailed search strategies for each electronic database without language restrictions. Reference lists of eligible studies and previous systematic reviews were also reviewed to identify further eligible studies.


## 2.3. Study Selection

Two review authors (Yang Xie and Xueqing Yu) independently examined titles and abstracts retrieved from the search and selected all potentially eligible studies. Then these full-text articles were obtained and the same review authors reviewed them independently against the inclusion and exclusion criteria. A third review author (Jiansheng Li) acted as an arbiter when consensus could not be reached.


## 2.4. Data Extraction

Data extraction was independently conducted by two review authors (Yang Xie and Xueqing Yu) using a standardized data extraction sheet, involving information of authors, year of publication, study design, participants, intervention, comparator, and outcomes, with a third review author (Jiansheng Li) acting as an arbiter when disagreements existed between Yang Xie and Xueqing Yu.


## 2.5. Assessment of Risk of Bias

Methodological quality was evaluated using the Cochrane tool for assessing risk of bias in RCTs [29]. Two review authors (Yang Xie and Xueqing Yu) independently assessed and scored each study with a third review author (Jiansheng Li) acting as an arbiter when disagreements existed.


## 2.6. Statistical Analysis

Statistical analysis was conducted by RevMan software (version 5.3) [30] and Stata software (version 12.0; StataCorp LP, USA). We summarized data using odds ratio (OR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. If the data could not be combined into a meta-analysis, we summarized them in the text. We used a χ2 test to estimate heterogeneity of both the MD and OR. Further analysis was performed using theI2 test. A random-effect model was used to interpret the results if heterogeneity was statistically significant, whereas a fixed-effect model was used if heterogeneity was not statistically significant. We regarded heterogeneity as substantial whenI2 was greater than 50% or a low P value (P<0.10) was reported for the χ2 test [31]. When more than 10 studies were included in the meta-analysis, we would investigate publication bias by funnel plots. In addition, a metaregression analysis was performed to explore potential associations between effect size and covariates of interest (publication year, region, intervention forms, sample size, and treatment period). If necessary, we conducted subgroup analysis to assess whether the treatment effects were different in different subgroups.


## 3. Results

### 3.1. Literature Search and Study Selection

We retrieved 600 records using the search strategy specified in our protocol. 223 records were discarded after reviewing the titles and/or abstracts. Thirty-five articles that initially appeared to meet the inclusion criteria were excluded with reasons: (i) not stable COPD (n=24), (ii) not targeted comparators (n=9), (iii) not targeted outcomes (n=1), and (iv) full-text articles unavailable (n=1). Thus, nineteen studies (1298 participants) finally met our criteria and were included in this review [7–25]. The study selection process was outlined in Figure 1.Figure 1
Study flow diagram.


### 3.2. Data Extraction and Assessment of Risk of Bias

A detailed description of the characteristics of included studies was outlined in Table1. We determined the Cochrane “risk of bias” score for each study and this information was summarized in Table 2 and Figures 2 and 3.Table 1
Characteristics of included studies.
Study Country Study design Participants Interventions Outcomes Notes Chu and Cai [7] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 15/17, CG: 14/18Age (range, years): from 46 to 80FEV1% predicted: EG: 56.83 ± 8.96; CG: 52.53 ± 13.96Course of disease (range): from 5 months to 20 yearsParticipants randomly assigned: 64 participants were randomly assigned Analyzed: EG: 32CG: 32 EG: AT + Chinese medicine + western medicineCG: Chinese medicine + western medicineDuration: treatment for 90 days; follow-up for 6 months Spirometry, acute exacerbation frequency, effective rate, adverse effects  Deering et al. [8] 2011 Ireland RCT, 3 arms Participant status: Gender (M/F): PR group: 11/14; AT + PR group: 8/8; CG: 12/7Age (years): PR group: 67.7 ± 5.3; AT + PR group: 65.1 ± 9.7; CG: 68.6 ± 5.5FEV1% predicted: PR group: 48.5 ± 16.1; AT + PR group: 48.8 ± 22.7; CG: 45.8 ± 18.3Participants randomly assigned: 60 participants were randomly assigned Analyzed:AT + PR group: 16PR group: 25 AT + PR group: AT + PRPR group: PR aloneCG: no interventionDuration: treatment for 7 weeks; follow-up for 3 months Body mass index, mMRC, the modified Borg dyspnea score, systemic inflammation, spirometry, total energy expenditure, physical activity duration, metabolic equivalents, steps per day, sleep time/efficiency, incremental shuttle walk test, SGRQ, EQ-5D Control group was not used in the analysis  Deng et al. [9] 2016 China RCT, 2 arms Participant status: Gender (M/F): EG: 13/9, CG: 15/7Age (years): EG: 57.1 ± 5.9; CG: 58.5 ± 6.5FEV1% predicted: EG: 52.4 ± 2.9; CG: 51.5 ± 2.7Course of disease (years): EG: 6.4 ± 2.5; CG: 6.3 ± 2.1Participants randomly assigned: 44 participants were randomly assigned Analyzed:EG: 22CG: 22 EG: abdominal AT + conventional therapyCG: conventional therapy aloneDuration: treatment for 24 weeks Annual hospital stay, annual acute exacerbation frequency, oxygen saturation level, spirometry, 6MWD  Feng et al. [10] 2016 China RCT, 2 arms Participant status: Gender (M/F): EG: 33/3, CG: 31/5Age (years): EG: 67.8 ± 5.4; CG: 67.1 ± 6.1FEV1% predicted: EG: 47.3 ± 17.1; CG: 43.9 ± 16.8Participants randomly assigned: 72 participants were randomly assigned Analyzed:EG: 33CG: 32 EG: AT + daily medicationCG: Sham acupuncture + daily medicationDuration: treatment 3 times weekly for 8 weeks 6MWD, modified Borg scale score before and after 6MWT, oxygen saturation during the 6MWT, spirometry, SGRQ  Gao et al. [11] 2011 China RCT, 2 arms Participant status: Gender (M/F): EG: 13/17, CG: 12/18Age (years): EG: 64.87 ± 8.73; CG: 65.25 ± 10.66FEV1% predicted: EG: 45.88 ± 5.05; CG: 43.54 ± 6.29Course of disease (years): EG: 10.31 ± 5.82; CG: 10.78 ± 5.53Participants randomly assigned: 61 participants were randomly assigned Analyzed:EG: 30CG: 30 EG: warm ATCG: drug therapyDuration: treatment for 8 weeks Spirometry, clinical symptoms, SGRQ  Hu [12] 2016 China RCT, 2 arms Participant status: Gender (M/F): not describedAge (years): not describedFEV1% predicted: not describedCourse of disease (years): not describedParticipants randomly assigned: 89 participants were randomly assigned Analyzed:EG: 45CG: 44 EG: warm AT + conventional therapyCG: spreading moxibustion + conventional therapyDuration: treatment for 2 months Effective rate, spirometry  Jia [13] 2004 China RCT, 3 arms Participant status: Gender (M/F): AT group: 9/13; PR group: 8/14; AT + PR group: 10/12Age (years): AT group: 61.0 ± 32.6; PR group: 60.0 ± 34.8; AT + PR group: 61.0 ± 33.2FEV1% predicted: AT group: 70.9 ± 0.2; PR group: 71.1 ± 0.1; AT + PR group: 70.6 ± 0.7Course of disease (years): AT group: 11.7 ± 8.9; PR group: 12.1 ± 7.2; AT + PR group: 11.6 ± 9.0Participants randomly assigned: 66 participants were randomly assigned Analyzed:AT group: 22PR group: 22AT + PR group: 22 AT group: AT + conventional drugsPR group: PR + conventional drugsAT + PR group: AT + PR + conventional drugsDuration: treatment for 100 days Effective rate, spirometry Data from AT group and AT + PR group were combined in the analysis  Li [14] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 19/10, CG: 17/13Age (years): EG: 57.21 ± 6.68; CG: 55.80 ± 7.23FEV1% predicted: EG: 66.28 ± 6.86; CG: 65.16 ± 6.16Course of disease (years): EG: 10.38 ± 4.90; CG: 10.70 ± 4.88Participants randomly assigned: 60 participants were randomly assigned Analyzed:EG: 29CG: 30 EG: warm AT + drug therapyCG: drug therapy aloneDuration: treatment for 1 month Safety indicators, CAT, spirometry, clinical symptoms, effective rate, adverse effects  Li et al. [15] 2016 China RCT, 2 arms Participant status: Gender (M/F): two groups were reported to be comparable in gender.Age (years): two groups were reported to be comparable in age.FEV1% predicted: EG: 53.1 ± 10.9; CG: 51.9 ± 11.4Participants randomly assigned: 60 participants were randomly assignedAnalyzed:EG: 30CG: 30 EG: AT + Chinese medicine + western medicineCG: Chinese medicine + western medicineDuration: treatment for 3 weeks Clinical symptoms, CAT, spirometry, effective rate, adverse effects  Liu et al. [16] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 24/16, CG: 26/14Age (years): EG: 58.3 ± 12.4; CG: 63.2 ± 10.7FEV1% predicted: EG: 35.71 ± 7.28; CG: 36.42 ± 6.42Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: AT + drug therapyCG: drug therapy aloneDuration: treatment for 3 months Clinical signs and symptoms, 6MWD, spirometry, effective rate  Suzuki et al. [17] 2012 Japan RCT, 2 arms Participant status: Gender (M/F): EG: 31/3, CG: 32/2Age (years): EG: 72.7 ± 6.8; CG: 72.5 ± 7.4FEV1% predicted: EG: 44.5 ± 16.3; CG: 48.0 ± 16.5Participants randomly assigned: 68 participants were randomly assigned Analyzed:EG: 30CG: 32 EG: AT + daily medicationCG: placebo acupuncture + daily medicationDuration: treatment once a week for 12 weeks 6MWD, modified Borg scale score before and after 6MWT, oxygen saturation during the 6MWT, spirometry, SGRQ, arterial blood gas, maximum inspiratory mouth pressure, maximum expiratory mouth pressure, range of motion in the rib cage, body mass index, serum prealbumin levels, MRC score, adverse reactions  Tong et al. [18] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 15/1, CG: 12/2Age (years): EG: 64 ± 6; CG: 67 ± 6FEV1% predicted: EG: 41.72 ± 17.95; CG: 36.16 ± 16.29Participants randomly assigned: 30 participants were randomly assigned Analyzed:EG: 16CG: 14 EG: AT + aerobic exerciseCG: placebo acupuncture + aerobic exerciseDuration: treatment for 5 weeks 6MWD, spirometry, maximum oxygen uptake, exercise time, SGRQ  Wan et al. [19] 2009 China RCT, 2 arms Participant status: Gender (M/F): EG: 47/28, CG: 45/30Age (years): EG: 62.40 ± 8.56; CG: 61.80 ± 10.10FEV1% predicted: EG: 48.07 ± 12.77; CG: 47.27 ± 14.02Course of disease (years): EG: 7.73 ± 3.80; CG: 7.70 ± 2.92Participants randomly assigned: 150 participants were randomly assigned Analyzed:EG: 75CG: 75 EG: AT + Chinese medicineCG: Chinese medicine aloneDuration: treatment for 36 days Effective rate, spirometry  Xie and Yu [20] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 22/18, CG: 18/22Age (years): EG: 68.9 ± 8.7; CG: 68.5 ± 9.6FEV1% predicted: EG: 45.89 ± 5.06; CG: 43.55 ± 6.30Course of disease (years): EG: 11.8 ± 6.5; CG: 12.3 ± 5.5Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: warm ATCG: drug therapyDuration: treatment for 8 weeks Spirometry, symptom scores  Yang et al. [21] 2009 China RCT, 2 arms Participant status: Gender (M/F): EG: 26/14, CG: 28/12Age (range, years): EG: from 49 to 78; CG: from 45 to 77FEV1% predicted: EG: 53.5 ± 19.2; CG: 54.3 ± 22.6Course of disease (mean, years): EG: 6.9; CG: 7.1Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: AT + PRCG: PR aloneDuration: treatment for 40 days COPD quality of life questionnaire, 6MWD, spirometry  Yu [22] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 18/12, CG: 17/13Age (years): EG: 63.0 ± 8.5; CG: 62.0 ± 7.6FEV1% predicted: EG: 50.23 ± 2.56; CG: 51.33 ± 2.43Course of disease (years): EG: 8.9 ± 3.7; CG: 8.4 ± 3.5Participants randomly assigned: 60 participants were randomly assigned Analyzed:EG: 30CG: 30 EG: warm AT + function trainingCG: conventional drug therapy + function trainingDuration: treatment for 3 months Arterial blood gas, spirometry, SGRQ, effective rate  Ge et al. [23] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 23/1, CG: 15/5Age (years): EG: 65 ± 6; CG: 65 ± 7FEV1% predicted: EG: 40.76 ± 16.36; CG: 40.53 ± 17.40Course of disease (years): EG: 9.1 ± 5.5; CG: 8.6 ± 6.8Participants randomly assigned: 44 participants were randomly assignedAnalyzed:EG: 22CG: 19 EG: AT + conventional drugs + aerobic exerciseCG: placebo acupuncture + conventional drugs + aerobic exerciseDuration: treatment for 14 times Body mass index, average distance and average maximum heart rate during bicycle exercise, 6MWD, maximum power and maximum heart rate during exercise cardiopulmonary function test, spirometry  Shi [24] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 18/12, CG: 17/14Age (years): EG: 57.77 ± 6.54; CG: 55.90 ± 6.86FEV1% predicted: EG: 64.11 ± 5.79; CG: 65.85 ± 6.86Course of disease (years): EG: 11.43 ± 4.37; CG: 11.68 ± 3.64Participants randomly assigned: 66 participants were randomly assignedAnalyzed:EG: 30CG: 31 EG: ATCG: western medicineDuration: treatment for 2 months CAT, spirometry, clinical symptoms, effective rate, safety indicators  Tang [25] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 19/11, CG: 18/13Age (years): EG: 57.47 ± 5.33; CG: 56.59 ± 6.34Course of disease (years): EG: 10.07 ± 2.20; CG: 10.55 ± 2.10Participants randomly assigned: 64 participants were randomly assignedAnalyzed:EG: 30CG: 29 EG: AT + western medicineCG: western medicine aloneDuration: treatment for 2 months CAT, clinical symptoms, 6MWT, effective rate, safety indicators RCT: randomized controlled trial, EG: experimental group, CG: control group, AT: acupuncture therapy, PR: pulmonary rehabilitation, FEV1: forced expiratory volume in 1 second, 6MWT/MWD: six-minute walk test/distance, SGRQ: St. George’s Respiratory Questionnaire, mMRC: modified Medical Research Council dyspnea scale, MRC: Medical Research Council dyspnea scale, CAT: COPD assessment test.Table 2
Risks of bias of included studies.
Study Random sequence generation Allocation concealment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other biases Chu and Cai [7] 2015 U U H U L U H Deering et al. [8] 2011 L U H L U U H Deng et al. [9] 2016 U U H U L U H Feng et al. [10] 2016 L L L L L U L Gao et al. [11] 2011 L U H U L U L Hu [12] 2016 U U H U L U L Jia [13] 2004 L U H U L U L Li [14] 2015 L U H U L U H Li et al. [15] 2016 L L H U L U L Liu et al. [16] 2015 U U H U L U H Suzuki et al. [17] 2012 L U L L L U L Tong et al. [18] 2014 L L L L L U L Wan et al. [19] 2009 U U H U L U L Xie and Yu [20] 2014 L U H U L U L Yang et al. [21] 2009 H U H U L U H Yu [22] 2014 L U H U L H L Ge et al. [23] 2017 L U L U L U L Shi [24] 2017 L U H U L U H Tang [25] 2017 L U H U L U H Notes. Quality assessment based on the Cochrane tools for assessing risk of bias. L: low (low risk of bias), H: high (high risk of bias), U: unclear (uncertain risk of bias).Figure 2
Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.Figure 3
Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.


### 3.3. Effects of Interventions

#### 3.3.1. 6MWD

Eight studies [9, 10, 16–18, 21, 23, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 65.96, P<0.00001; I2 = 89%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 47.84; 95% CI: 23.33 to 72.35; Z = 3.83, P=0.0001) (Figure 4).Figure 4
Experimental group versus control group, 6MWD.


#### 3.3.2. SGRQ

Five studies [8, 10, 11, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 39.18, P<0.00001; I2 = 90%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in SGRQ total scores between two groups (MD: −6.58; 95% CI: −13.19 to 0.03; Z = 1.95, P=0.05) (Figure 5).Figure 5
Experimental group versus control group, SGRQ total scores.Two studies [10, 17] provided numerical data for symptom domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.05, P=0.83; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that symptom domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −24.86; 95% CI: −32.17 to −17.55; Z = 6.66, P<0.00001) (Figure 6).Figure 6
Experimental group versus control group, symptom domain scores of SGRQ.Two studies [10, 17] provided numerical data for activity domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.04, P=0.84; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that activity domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −16.52; 95% CI: −22.57 to −10.47; Z = 5.36, P<0.00001) (Figure 7).Figure 7
Experimental group versus control group, activity domain scores of SGRQ.Two studies [10, 17] provided numerical data for impact domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P=0.97; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that impact domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −13.07; 95% CI: −17.23 to −8.92; Z = 6.16, P<0.00001) (Figure 8).Figure 8
Experimental group versus control group, impact domain scores of SGRQ.


#### 3.3.3. FEV1

Seven studies [7, 11, 12, 17, 19, 20, 22] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 30.40, P<0.0001; I2 = 80%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in FEV1 between two groups (MD: 0.13; 95% CI: −0.05 to 0.31; Z = 1.44, P=0.15) (Figure 9).Figure 9
Experimental group versus control group, FEV1.


#### 3.3.4. Effective Rate

Ten studies [7, 12–16, 19, 22, 24, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 8.33, P=0.50; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.26; 95% CI: 1.43 to 3.58; Z = 3.48, P=0.0005) (Figure 10).Figure 10
Experimental group versus control group, effective rate.


#### 3.3.5. mMRC

Only one study [8] provided numerical data for mMRC scores; thus, the meta-analysis was not performed. Changes from baseline in mMRC scores in AT plus pulmonary rehabilitation (PR) group and PR group were −0.3±0.5 and −0.3±0.9, respectively. There was significant difference reported within AT plus PR group (P=0.04).


### 3.4. Adverse Effects

Six studies [7, 14, 15, 17, 24, 25] provided information about adverse effects. Only one study [17] reported some minor adverse reactions during the trial including fatigue, subcutaneous hemorrhage, dizziness, and needle site pain, and the remaining 5 studies [7, 14, 15, 24, 25] reported no adverse effects.


### 3.5. Metaregression Analysis

We tried to perform a univariate metaregression analysis to explore potential associations between effect size and covariates of interest (publication year, region, intervention forms, sample size, and treatment period) (see Table3). However, the results showed that there were no statistically significant associations among them, and this might be due to the insufficient number of studies included [32].Table 3
Univariate metaregression analysis of covariates of interest.
Covariates of interest Coefficient Standard error (SE) t P 95% confidence intervals (CI) Lower limit Upper limit Six-minute walk distance Publication year 2.812 4.479 0.63 0.553 −8.148 13.773 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms 26.947 21.520 1.25 0.257 −25.710 79.603 Sample size −0.236 0.716 −0.33 0.753 −1.988 1.516 Treatment period −0.115 0.292 −0.39 0.707 −0.829 0.599 SGRQ Publication year −1.634 2.107 −0.78 0.495 −8.340 5.072 Region 8.595 9.520 0.90 0.433 −21.702 38.891 Intervention forms 4.605 4.389 1.05 0.371 −9.363 18.573 Sample size −0.382 0.225 −1.70 0.188 −1.097 0.334 Treatment period −0.342 0.139 −2.47 0.090 −0.783 0.099 FEV 1 Publication year −0.028 0.043 −0.65 0.544 −0.139 0.083 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms −0.086 0.088 −0.98 0.371 −0.313 0.140 Sample size 0.003 0.003 0.83 0.447 −0.005 0.011 Treatment period 0.002 0.005 0.48 0.654 −0.011 0.016 Effective rate Publication year −0.064 0.060 −1.07 0.315 −0.203 0.074 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms −0.117 0.301 −0.39 0.707 −0.812 0.577 Sample size −0.002 0.008 −0.22 0.830 −0.021 0.017 Treatment period 0.015 0.010 1.54 0.163 −0.008 0.037 Note. 6MWD: six-minute walk test/distance, SGRQ: St. George’s Respiratory Questionnaire. The∗ region was the same.


### 3.6. Subgroup Analysis (AT Adjunctive to Other Treatments versus Placebo or Sham Acupuncture Adjunctive to Other Treatments)

#### 3.6.1. 6MWD

Four studies [10, 17, 18, 23] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 9.17, P=0.03; I2 = 67%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 63.05; 95% CI: 39.27 to 86.83; Z = 5.20, P<0.00001) (Figure 11).Figure 11
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, 6MWD.


#### 3.6.2. SGRQ

Three studies [10, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 22.16, P<0.0001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that SGRQ total scores in the experimental group improved more compared to the control group (MD: −10.66; 95% CI: −22.24 to 0.92; Z = 1.80, P=0.07) (Figure 12).Figure 12
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, SGRQ total scores.


#### 3.6.3. FEV1

Only one study [17] provided numerical data for FEV1; thus, the meta-analysis was not performed. Changes from baseline in FEV1 in experimental group and control group were 0.07±0.3 and −0.04±0.2, respectively. However, the P values were not available.


### 3.7. Subgroup Analysis (AT Adjunctive to Other Treatments versus Other Treatments Alone)

#### 3.7.1. 6MWD

Four studies [9, 16, 21, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 32.35, P<0.00001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 35.15; 95% CI: 2.37 to 67.92; Z = 2.10, P=0.04) (Figure 13).Figure 13
AT adjunctive to other treatments versus other treatments alone, 6MWD.


#### 3.7.2. SGRQ

Only one study [8] provided numerical data for SGRQ total scores; thus, the meta-analysis was not performed. Compared to the control group (7.0±14.9), both AT plus PR group and PR group demonstrated a significant change for SGRQ total scores (−7.1±12.7, P=0.01; −7.4±8.7, P=0.0006). However, there were no data available for symptom domain scores, activity domain scores, and impact domain scores of SGRQ.


#### 3.7.3. FEV1

Two studies [7, 19] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P = 1.00; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that FEV1 in the experimental group improved more compared to the control group (MD: 0.41; 95% CI: 0.28 to 0.54; Z = 6.01, P<0.00001) (Figure 14).Figure 14
AT adjunctive to other treatments versus other treatments alone, FEV1.


#### 3.7.4. Effective Rate

Seven studies [7, 13–16, 19, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 2.38, P=0.88; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.84; 95% CI: 1.59 to 5.06; Z = 3.53, P=0.0004) (Figure 15).Figure 15
AT adjunctive to other treatments versus other treatments alone, effective rate.


### 3.8. Reporting Biases

We did not investigate publication biases by funnel plot because each comparison included not more than 10 studies.


## 3.1. Literature Search and Study Selection

We retrieved 600 records using the search strategy specified in our protocol. 223 records were discarded after reviewing the titles and/or abstracts. Thirty-five articles that initially appeared to meet the inclusion criteria were excluded with reasons: (i) not stable COPD (n=24), (ii) not targeted comparators (n=9), (iii) not targeted outcomes (n=1), and (iv) full-text articles unavailable (n=1). Thus, nineteen studies (1298 participants) finally met our criteria and were included in this review [7–25]. The study selection process was outlined in Figure 1.Figure 1
Study flow diagram.


## 3.2. Data Extraction and Assessment of Risk of Bias

A detailed description of the characteristics of included studies was outlined in Table1. We determined the Cochrane “risk of bias” score for each study and this information was summarized in Table 2 and Figures 2 and 3.Table 1
Characteristics of included studies.
Study Country Study design Participants Interventions Outcomes Notes Chu and Cai [7] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 15/17, CG: 14/18Age (range, years): from 46 to 80FEV1% predicted: EG: 56.83 ± 8.96; CG: 52.53 ± 13.96Course of disease (range): from 5 months to 20 yearsParticipants randomly assigned: 64 participants were randomly assigned Analyzed: EG: 32CG: 32 EG: AT + Chinese medicine + western medicineCG: Chinese medicine + western medicineDuration: treatment for 90 days; follow-up for 6 months Spirometry, acute exacerbation frequency, effective rate, adverse effects  Deering et al. [8] 2011 Ireland RCT, 3 arms Participant status: Gender (M/F): PR group: 11/14; AT + PR group: 8/8; CG: 12/7Age (years): PR group: 67.7 ± 5.3; AT + PR group: 65.1 ± 9.7; CG: 68.6 ± 5.5FEV1% predicted: PR group: 48.5 ± 16.1; AT + PR group: 48.8 ± 22.7; CG: 45.8 ± 18.3Participants randomly assigned: 60 participants were randomly assigned Analyzed:AT + PR group: 16PR group: 25 AT + PR group: AT + PRPR group: PR aloneCG: no interventionDuration: treatment for 7 weeks; follow-up for 3 months Body mass index, mMRC, the modified Borg dyspnea score, systemic inflammation, spirometry, total energy expenditure, physical activity duration, metabolic equivalents, steps per day, sleep time/efficiency, incremental shuttle walk test, SGRQ, EQ-5D Control group was not used in the analysis  Deng et al. [9] 2016 China RCT, 2 arms Participant status: Gender (M/F): EG: 13/9, CG: 15/7Age (years): EG: 57.1 ± 5.9; CG: 58.5 ± 6.5FEV1% predicted: EG: 52.4 ± 2.9; CG: 51.5 ± 2.7Course of disease (years): EG: 6.4 ± 2.5; CG: 6.3 ± 2.1Participants randomly assigned: 44 participants were randomly assigned Analyzed:EG: 22CG: 22 EG: abdominal AT + conventional therapyCG: conventional therapy aloneDuration: treatment for 24 weeks Annual hospital stay, annual acute exacerbation frequency, oxygen saturation level, spirometry, 6MWD  Feng et al. [10] 2016 China RCT, 2 arms Participant status: Gender (M/F): EG: 33/3, CG: 31/5Age (years): EG: 67.8 ± 5.4; CG: 67.1 ± 6.1FEV1% predicted: EG: 47.3 ± 17.1; CG: 43.9 ± 16.8Participants randomly assigned: 72 participants were randomly assigned Analyzed:EG: 33CG: 32 EG: AT + daily medicationCG: Sham acupuncture + daily medicationDuration: treatment 3 times weekly for 8 weeks 6MWD, modified Borg scale score before and after 6MWT, oxygen saturation during the 6MWT, spirometry, SGRQ  Gao et al. [11] 2011 China RCT, 2 arms Participant status: Gender (M/F): EG: 13/17, CG: 12/18Age (years): EG: 64.87 ± 8.73; CG: 65.25 ± 10.66FEV1% predicted: EG: 45.88 ± 5.05; CG: 43.54 ± 6.29Course of disease (years): EG: 10.31 ± 5.82; CG: 10.78 ± 5.53Participants randomly assigned: 61 participants were randomly assigned Analyzed:EG: 30CG: 30 EG: warm ATCG: drug therapyDuration: treatment for 8 weeks Spirometry, clinical symptoms, SGRQ  Hu [12] 2016 China RCT, 2 arms Participant status: Gender (M/F): not describedAge (years): not describedFEV1% predicted: not describedCourse of disease (years): not describedParticipants randomly assigned: 89 participants were randomly assigned Analyzed:EG: 45CG: 44 EG: warm AT + conventional therapyCG: spreading moxibustion + conventional therapyDuration: treatment for 2 months Effective rate, spirometry  Jia [13] 2004 China RCT, 3 arms Participant status: Gender (M/F): AT group: 9/13; PR group: 8/14; AT + PR group: 10/12Age (years): AT group: 61.0 ± 32.6; PR group: 60.0 ± 34.8; AT + PR group: 61.0 ± 33.2FEV1% predicted: AT group: 70.9 ± 0.2; PR group: 71.1 ± 0.1; AT + PR group: 70.6 ± 0.7Course of disease (years): AT group: 11.7 ± 8.9; PR group: 12.1 ± 7.2; AT + PR group: 11.6 ± 9.0Participants randomly assigned: 66 participants were randomly assigned Analyzed:AT group: 22PR group: 22AT + PR group: 22 AT group: AT + conventional drugsPR group: PR + conventional drugsAT + PR group: AT + PR + conventional drugsDuration: treatment for 100 days Effective rate, spirometry Data from AT group and AT + PR group were combined in the analysis  Li [14] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 19/10, CG: 17/13Age (years): EG: 57.21 ± 6.68; CG: 55.80 ± 7.23FEV1% predicted: EG: 66.28 ± 6.86; CG: 65.16 ± 6.16Course of disease (years): EG: 10.38 ± 4.90; CG: 10.70 ± 4.88Participants randomly assigned: 60 participants were randomly assigned Analyzed:EG: 29CG: 30 EG: warm AT + drug therapyCG: drug therapy aloneDuration: treatment for 1 month Safety indicators, CAT, spirometry, clinical symptoms, effective rate, adverse effects  Li et al. [15] 2016 China RCT, 2 arms Participant status: Gender (M/F): two groups were reported to be comparable in gender.Age (years): two groups were reported to be comparable in age.FEV1% predicted: EG: 53.1 ± 10.9; CG: 51.9 ± 11.4Participants randomly assigned: 60 participants were randomly assignedAnalyzed:EG: 30CG: 30 EG: AT + Chinese medicine + western medicineCG: Chinese medicine + western medicineDuration: treatment for 3 weeks Clinical symptoms, CAT, spirometry, effective rate, adverse effects  Liu et al. [16] 2015 China RCT, 2 arms Participant status: Gender (M/F): EG: 24/16, CG: 26/14Age (years): EG: 58.3 ± 12.4; CG: 63.2 ± 10.7FEV1% predicted: EG: 35.71 ± 7.28; CG: 36.42 ± 6.42Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: AT + drug therapyCG: drug therapy aloneDuration: treatment for 3 months Clinical signs and symptoms, 6MWD, spirometry, effective rate  Suzuki et al. [17] 2012 Japan RCT, 2 arms Participant status: Gender (M/F): EG: 31/3, CG: 32/2Age (years): EG: 72.7 ± 6.8; CG: 72.5 ± 7.4FEV1% predicted: EG: 44.5 ± 16.3; CG: 48.0 ± 16.5Participants randomly assigned: 68 participants were randomly assigned Analyzed:EG: 30CG: 32 EG: AT + daily medicationCG: placebo acupuncture + daily medicationDuration: treatment once a week for 12 weeks 6MWD, modified Borg scale score before and after 6MWT, oxygen saturation during the 6MWT, spirometry, SGRQ, arterial blood gas, maximum inspiratory mouth pressure, maximum expiratory mouth pressure, range of motion in the rib cage, body mass index, serum prealbumin levels, MRC score, adverse reactions  Tong et al. [18] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 15/1, CG: 12/2Age (years): EG: 64 ± 6; CG: 67 ± 6FEV1% predicted: EG: 41.72 ± 17.95; CG: 36.16 ± 16.29Participants randomly assigned: 30 participants were randomly assigned Analyzed:EG: 16CG: 14 EG: AT + aerobic exerciseCG: placebo acupuncture + aerobic exerciseDuration: treatment for 5 weeks 6MWD, spirometry, maximum oxygen uptake, exercise time, SGRQ  Wan et al. [19] 2009 China RCT, 2 arms Participant status: Gender (M/F): EG: 47/28, CG: 45/30Age (years): EG: 62.40 ± 8.56; CG: 61.80 ± 10.10FEV1% predicted: EG: 48.07 ± 12.77; CG: 47.27 ± 14.02Course of disease (years): EG: 7.73 ± 3.80; CG: 7.70 ± 2.92Participants randomly assigned: 150 participants were randomly assigned Analyzed:EG: 75CG: 75 EG: AT + Chinese medicineCG: Chinese medicine aloneDuration: treatment for 36 days Effective rate, spirometry  Xie and Yu [20] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 22/18, CG: 18/22Age (years): EG: 68.9 ± 8.7; CG: 68.5 ± 9.6FEV1% predicted: EG: 45.89 ± 5.06; CG: 43.55 ± 6.30Course of disease (years): EG: 11.8 ± 6.5; CG: 12.3 ± 5.5Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: warm ATCG: drug therapyDuration: treatment for 8 weeks Spirometry, symptom scores  Yang et al. [21] 2009 China RCT, 2 arms Participant status: Gender (M/F): EG: 26/14, CG: 28/12Age (range, years): EG: from 49 to 78; CG: from 45 to 77FEV1% predicted: EG: 53.5 ± 19.2; CG: 54.3 ± 22.6Course of disease (mean, years): EG: 6.9; CG: 7.1Participants randomly assigned: 80 participants were randomly assigned Analyzed:EG: 40CG: 40 EG: AT + PRCG: PR aloneDuration: treatment for 40 days COPD quality of life questionnaire, 6MWD, spirometry  Yu [22] 2014 China RCT, 2 arms Participant status: Gender (M/F): EG: 18/12, CG: 17/13Age (years): EG: 63.0 ± 8.5; CG: 62.0 ± 7.6FEV1% predicted: EG: 50.23 ± 2.56; CG: 51.33 ± 2.43Course of disease (years): EG: 8.9 ± 3.7; CG: 8.4 ± 3.5Participants randomly assigned: 60 participants were randomly assigned Analyzed:EG: 30CG: 30 EG: warm AT + function trainingCG: conventional drug therapy + function trainingDuration: treatment for 3 months Arterial blood gas, spirometry, SGRQ, effective rate  Ge et al. [23] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 23/1, CG: 15/5Age (years): EG: 65 ± 6; CG: 65 ± 7FEV1% predicted: EG: 40.76 ± 16.36; CG: 40.53 ± 17.40Course of disease (years): EG: 9.1 ± 5.5; CG: 8.6 ± 6.8Participants randomly assigned: 44 participants were randomly assignedAnalyzed:EG: 22CG: 19 EG: AT + conventional drugs + aerobic exerciseCG: placebo acupuncture + conventional drugs + aerobic exerciseDuration: treatment for 14 times Body mass index, average distance and average maximum heart rate during bicycle exercise, 6MWD, maximum power and maximum heart rate during exercise cardiopulmonary function test, spirometry  Shi [24] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 18/12, CG: 17/14Age (years): EG: 57.77 ± 6.54; CG: 55.90 ± 6.86FEV1% predicted: EG: 64.11 ± 5.79; CG: 65.85 ± 6.86Course of disease (years): EG: 11.43 ± 4.37; CG: 11.68 ± 3.64Participants randomly assigned: 66 participants were randomly assignedAnalyzed:EG: 30CG: 31 EG: ATCG: western medicineDuration: treatment for 2 months CAT, spirometry, clinical symptoms, effective rate, safety indicators  Tang [25] 2017 China RCT, 2 arms Participant status: Gender (M/F): EG: 19/11, CG: 18/13Age (years): EG: 57.47 ± 5.33; CG: 56.59 ± 6.34Course of disease (years): EG: 10.07 ± 2.20; CG: 10.55 ± 2.10Participants randomly assigned: 64 participants were randomly assignedAnalyzed:EG: 30CG: 29 EG: AT + western medicineCG: western medicine aloneDuration: treatment for 2 months CAT, clinical symptoms, 6MWT, effective rate, safety indicators RCT: randomized controlled trial, EG: experimental group, CG: control group, AT: acupuncture therapy, PR: pulmonary rehabilitation, FEV1: forced expiratory volume in 1 second, 6MWT/MWD: six-minute walk test/distance, SGRQ: St. George’s Respiratory Questionnaire, mMRC: modified Medical Research Council dyspnea scale, MRC: Medical Research Council dyspnea scale, CAT: COPD assessment test.Table 2
Risks of bias of included studies.
Study Random sequence generation Allocation concealment Blinding of participants and personnel Blinding of outcome assessment Incomplete outcome data Selective reporting Other biases Chu and Cai [7] 2015 U U H U L U H Deering et al. [8] 2011 L U H L U U H Deng et al. [9] 2016 U U H U L U H Feng et al. [10] 2016 L L L L L U L Gao et al. [11] 2011 L U H U L U L Hu [12] 2016 U U H U L U L Jia [13] 2004 L U H U L U L Li [14] 2015 L U H U L U H Li et al. [15] 2016 L L H U L U L Liu et al. [16] 2015 U U H U L U H Suzuki et al. [17] 2012 L U L L L U L Tong et al. [18] 2014 L L L L L U L Wan et al. [19] 2009 U U H U L U L Xie and Yu [20] 2014 L U H U L U L Yang et al. [21] 2009 H U H U L U H Yu [22] 2014 L U H U L H L Ge et al. [23] 2017 L U L U L U L Shi [24] 2017 L U H U L U H Tang [25] 2017 L U H U L U H Notes. Quality assessment based on the Cochrane tools for assessing risk of bias. L: low (low risk of bias), H: high (high risk of bias), U: unclear (uncertain risk of bias).Figure 2
Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.Figure 3
Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.


## 3.3. Effects of Interventions

### 3.3.1. 6MWD

Eight studies [9, 10, 16–18, 21, 23, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 65.96, P<0.00001; I2 = 89%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 47.84; 95% CI: 23.33 to 72.35; Z = 3.83, P=0.0001) (Figure 4).Figure 4
Experimental group versus control group, 6MWD.


### 3.3.2. SGRQ

Five studies [8, 10, 11, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 39.18, P<0.00001; I2 = 90%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in SGRQ total scores between two groups (MD: −6.58; 95% CI: −13.19 to 0.03; Z = 1.95, P=0.05) (Figure 5).Figure 5
Experimental group versus control group, SGRQ total scores.Two studies [10, 17] provided numerical data for symptom domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.05, P=0.83; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that symptom domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −24.86; 95% CI: −32.17 to −17.55; Z = 6.66, P<0.00001) (Figure 6).Figure 6
Experimental group versus control group, symptom domain scores of SGRQ.Two studies [10, 17] provided numerical data for activity domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.04, P=0.84; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that activity domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −16.52; 95% CI: −22.57 to −10.47; Z = 5.36, P<0.00001) (Figure 7).Figure 7
Experimental group versus control group, activity domain scores of SGRQ.Two studies [10, 17] provided numerical data for impact domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P=0.97; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that impact domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −13.07; 95% CI: −17.23 to −8.92; Z = 6.16, P<0.00001) (Figure 8).Figure 8
Experimental group versus control group, impact domain scores of SGRQ.


### 3.3.3. FEV1

Seven studies [7, 11, 12, 17, 19, 20, 22] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 30.40, P<0.0001; I2 = 80%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in FEV1 between two groups (MD: 0.13; 95% CI: −0.05 to 0.31; Z = 1.44, P=0.15) (Figure 9).Figure 9
Experimental group versus control group, FEV1.


### 3.3.4. Effective Rate

Ten studies [7, 12–16, 19, 22, 24, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 8.33, P=0.50; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.26; 95% CI: 1.43 to 3.58; Z = 3.48, P=0.0005) (Figure 10).Figure 10
Experimental group versus control group, effective rate.


### 3.3.5. mMRC

Only one study [8] provided numerical data for mMRC scores; thus, the meta-analysis was not performed. Changes from baseline in mMRC scores in AT plus pulmonary rehabilitation (PR) group and PR group were −0.3±0.5 and −0.3±0.9, respectively. There was significant difference reported within AT plus PR group (P=0.04).


## 3.3.1. 6MWD

Eight studies [9, 10, 16–18, 21, 23, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 65.96, P<0.00001; I2 = 89%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 47.84; 95% CI: 23.33 to 72.35; Z = 3.83, P=0.0001) (Figure 4).Figure 4
Experimental group versus control group, 6MWD.


## 3.3.2. SGRQ

Five studies [8, 10, 11, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 39.18, P<0.00001; I2 = 90%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in SGRQ total scores between two groups (MD: −6.58; 95% CI: −13.19 to 0.03; Z = 1.95, P=0.05) (Figure 5).Figure 5
Experimental group versus control group, SGRQ total scores.Two studies [10, 17] provided numerical data for symptom domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.05, P=0.83; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that symptom domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −24.86; 95% CI: −32.17 to −17.55; Z = 6.66, P<0.00001) (Figure 6).Figure 6
Experimental group versus control group, symptom domain scores of SGRQ.Two studies [10, 17] provided numerical data for activity domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.04, P=0.84; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that activity domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −16.52; 95% CI: −22.57 to −10.47; Z = 5.36, P<0.00001) (Figure 7).Figure 7
Experimental group versus control group, activity domain scores of SGRQ.Two studies [10, 17] provided numerical data for impact domain scores of SGRQ and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P=0.97; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that impact domain scores of SGRQ in the experimental group improved more compared to the control group (MD: −13.07; 95% CI: −17.23 to −8.92; Z = 6.16, P<0.00001) (Figure 8).Figure 8
Experimental group versus control group, impact domain scores of SGRQ.


## 3.3.3. FEV1

Seven studies [7, 11, 12, 17, 19, 20, 22] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 30.40, P<0.0001; I2 = 80%); hence, a random-effect model was used. The pooled results showed that there was no significant improvement in FEV1 between two groups (MD: 0.13; 95% CI: −0.05 to 0.31; Z = 1.44, P=0.15) (Figure 9).Figure 9
Experimental group versus control group, FEV1.


## 3.3.4. Effective Rate

Ten studies [7, 12–16, 19, 22, 24, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 8.33, P=0.50; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.26; 95% CI: 1.43 to 3.58; Z = 3.48, P=0.0005) (Figure 10).Figure 10
Experimental group versus control group, effective rate.


## 3.3.5. mMRC

Only one study [8] provided numerical data for mMRC scores; thus, the meta-analysis was not performed. Changes from baseline in mMRC scores in AT plus pulmonary rehabilitation (PR) group and PR group were −0.3±0.5 and −0.3±0.9, respectively. There was significant difference reported within AT plus PR group (P=0.04).


## 3.4. Adverse Effects

Six studies [7, 14, 15, 17, 24, 25] provided information about adverse effects. Only one study [17] reported some minor adverse reactions during the trial including fatigue, subcutaneous hemorrhage, dizziness, and needle site pain, and the remaining 5 studies [7, 14, 15, 24, 25] reported no adverse effects.


## 3.5. Metaregression Analysis

We tried to perform a univariate metaregression analysis to explore potential associations between effect size and covariates of interest (publication year, region, intervention forms, sample size, and treatment period) (see Table3). However, the results showed that there were no statistically significant associations among them, and this might be due to the insufficient number of studies included [32].Table 3
Univariate metaregression analysis of covariates of interest.
Covariates of interest Coefficient Standard error (SE) t P 95% confidence intervals (CI) Lower limit Upper limit Six-minute walk distance Publication year 2.812 4.479 0.63 0.553 −8.148 13.773 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms 26.947 21.520 1.25 0.257 −25.710 79.603 Sample size −0.236 0.716 −0.33 0.753 −1.988 1.516 Treatment period −0.115 0.292 −0.39 0.707 −0.829 0.599 SGRQ Publication year −1.634 2.107 −0.78 0.495 −8.340 5.072 Region 8.595 9.520 0.90 0.433 −21.702 38.891 Intervention forms 4.605 4.389 1.05 0.371 −9.363 18.573 Sample size −0.382 0.225 −1.70 0.188 −1.097 0.334 Treatment period −0.342 0.139 −2.47 0.090 −0.783 0.099 FEV 1 Publication year −0.028 0.043 −0.65 0.544 −0.139 0.083 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms −0.086 0.088 −0.98 0.371 −0.313 0.140 Sample size 0.003 0.003 0.83 0.447 −0.005 0.011 Treatment period 0.002 0.005 0.48 0.654 −0.011 0.016 Effective rate Publication year −0.064 0.060 −1.07 0.315 −0.203 0.074 Region ∗ ∗ ∗ ∗ ∗ ∗ Intervention forms −0.117 0.301 −0.39 0.707 −0.812 0.577 Sample size −0.002 0.008 −0.22 0.830 −0.021 0.017 Treatment period 0.015 0.010 1.54 0.163 −0.008 0.037 Note. 6MWD: six-minute walk test/distance, SGRQ: St. George’s Respiratory Questionnaire. The∗ region was the same.


## 3.6. Subgroup Analysis (AT Adjunctive to Other Treatments versus Placebo or Sham Acupuncture Adjunctive to Other Treatments)

### 3.6.1. 6MWD

Four studies [10, 17, 18, 23] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 9.17, P=0.03; I2 = 67%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 63.05; 95% CI: 39.27 to 86.83; Z = 5.20, P<0.00001) (Figure 11).Figure 11
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, 6MWD.


### 3.6.2. SGRQ

Three studies [10, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 22.16, P<0.0001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that SGRQ total scores in the experimental group improved more compared to the control group (MD: −10.66; 95% CI: −22.24 to 0.92; Z = 1.80, P=0.07) (Figure 12).Figure 12
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, SGRQ total scores.


### 3.6.3. FEV1

Only one study [17] provided numerical data for FEV1; thus, the meta-analysis was not performed. Changes from baseline in FEV1 in experimental group and control group were 0.07±0.3 and −0.04±0.2, respectively. However, the P values were not available.


## 3.6.1. 6MWD

Four studies [10, 17, 18, 23] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 9.17, P=0.03; I2 = 67%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 63.05; 95% CI: 39.27 to 86.83; Z = 5.20, P<0.00001) (Figure 11).Figure 11
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, 6MWD.


## 3.6.2. SGRQ

Three studies [10, 17, 18] provided numerical data for SGRQ total scores and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 22.16, P<0.0001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that SGRQ total scores in the experimental group improved more compared to the control group (MD: −10.66; 95% CI: −22.24 to 0.92; Z = 1.80, P=0.07) (Figure 12).Figure 12
AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments, SGRQ total scores.


## 3.6.3. FEV1

Only one study [17] provided numerical data for FEV1; thus, the meta-analysis was not performed. Changes from baseline in FEV1 in experimental group and control group were 0.07±0.3 and −0.04±0.2, respectively. However, the P values were not available.


## 3.7. Subgroup Analysis (AT Adjunctive to Other Treatments versus Other Treatments Alone)

### 3.7.1. 6MWD

Four studies [9, 16, 21, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 32.35, P<0.00001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 35.15; 95% CI: 2.37 to 67.92; Z = 2.10, P=0.04) (Figure 13).Figure 13
AT adjunctive to other treatments versus other treatments alone, 6MWD.


### 3.7.2. SGRQ

Only one study [8] provided numerical data for SGRQ total scores; thus, the meta-analysis was not performed. Compared to the control group (7.0±14.9), both AT plus PR group and PR group demonstrated a significant change for SGRQ total scores (−7.1±12.7, P=0.01; −7.4±8.7, P=0.0006). However, there were no data available for symptom domain scores, activity domain scores, and impact domain scores of SGRQ.


### 3.7.3. FEV1

Two studies [7, 19] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P = 1.00; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that FEV1 in the experimental group improved more compared to the control group (MD: 0.41; 95% CI: 0.28 to 0.54; Z = 6.01, P<0.00001) (Figure 14).Figure 14
AT adjunctive to other treatments versus other treatments alone, FEV1.


### 3.7.4. Effective Rate

Seven studies [7, 13–16, 19, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 2.38, P=0.88; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.84; 95% CI: 1.59 to 5.06; Z = 3.53, P=0.0004) (Figure 15).Figure 15
AT adjunctive to other treatments versus other treatments alone, effective rate.


## 3.7.1. 6MWD

Four studies [9, 16, 21, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity (χ2 = 32.35, P<0.00001; I2 = 91%); hence, a random-effect model was used. The pooled results showed that 6MWD in the experimental group improved more compared to the control group (MD: 35.15; 95% CI: 2.37 to 67.92; Z = 2.10, P=0.04) (Figure 13).Figure 13
AT adjunctive to other treatments versus other treatments alone, 6MWD.


## 3.7.2. SGRQ

Only one study [8] provided numerical data for SGRQ total scores; thus, the meta-analysis was not performed. Compared to the control group (7.0±14.9), both AT plus PR group and PR group demonstrated a significant change for SGRQ total scores (−7.1±12.7, P=0.01; −7.4±8.7, P=0.0006). However, there were no data available for symptom domain scores, activity domain scores, and impact domain scores of SGRQ.


## 3.7.3. FEV1

Two studies [7, 19] provided numerical data for FEV1 and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 0.00, P = 1.00; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that FEV1 in the experimental group improved more compared to the control group (MD: 0.41; 95% CI: 0.28 to 0.54; Z = 6.01, P<0.00001) (Figure 14).Figure 14
AT adjunctive to other treatments versus other treatments alone, FEV1.


## 3.7.4. Effective Rate

Seven studies [7, 13–16, 19, 25] provided categorical data for effective rate and were included in the meta-analysis. Analysis of the data indicated that heterogeneity was not statistically significant (χ2 = 2.38, P=0.88; I2 = 0%); hence, a fixed-effect model was used. The pooled results showed that effective rate in the experimental group was higher compared to the control group (OR: 2.84; 95% CI: 1.59 to 5.06; Z = 3.53, P=0.0004) (Figure 15).Figure 15
AT adjunctive to other treatments versus other treatments alone, effective rate.


## 3.8. Reporting Biases

We did not investigate publication biases by funnel plot because each comparison included not more than 10 studies.


## 4. Discussion

This systematic review provided a detailed summary of the current evidences related to the efficacy and safety of AT for functional effects and quality of life in COPD patients.6MWD is an important measure of functional exercise capacity of patients with COPD. The distance walked is associated with clinical outcomes such as hospitalization and mortality, and its changes are used to evaluate the efficacy of therapeutic interventions such as pulmonary rehabilitation, surgery, and pharmaceutical management [33, 34]. In this review, 6MWD in the experimental group improved more compared to the control group, and the MD was 47.84 meters, which was greater than 25 meters, the minimal clinically important difference (MCID) of 6MWD for COPD patients [34]. This result might indicate the potential of AT in improving exercise capacity of COPD patients. Two subgroup analyses supported this result as well, and the MD of 6MWD change was 63.05 meters and 35.15 meters, respectively.SGRQ, another primary outcome measure in this review, is a well-established disease-specific instrument to measure quality of life for asthma and COPD. In this review, there was no statistically significant improvement in SGRQ total scores between two groups. However, MD of symptom domain scores, activity domain scores, and impact domain scores of SGRQ was 24.86 units, 16.52 units, and 13.07 units, respectively. Although there was no MCID available for each domain, each MD was at least three times greater than 4 units, the MCID for SGRQ total scores in COPD patients [35], and this might suggest the effect of AT on different aspects of health status in COPD patients. Subgroup analysis (AT adjunctive to other treatments versus placebo or sham acupuncture adjunctive to other treatments) supported these above results as well.FEV1 is widely used by physicians in the diagnosis, classification, treatment, monitoring, and establishing prognosis for COPD patients. In this review, there was no statistically significant improvement in FEV1 between two groups. However, subgroup analysis (AT adjunctive to other treatments versus other treatments alone) showed MD of FEV1 change was 410 mL, which was four times greater than 100 mL, the MCID of FEV1 for COPD patients [36]. And this result might suggest the potential of AT in improving pulmonary function in COPD patients.mMRC is a major instrument to measure breathlessness. In this review, since mMRC scores were only available in one study, the meta-analysis was not performed. According to this study, change from baseline in mMRC scores in AT plus PR group and PR group was 0.3 units in both, and it was reported that there was significant difference within AT plus PR group. However, it was limited to support the effect of AT in improving breathlessness in COPD patients.Effective rate, an important outcome measure in clinical studies of Chinese medicine, was also evaluated. In this review, effective rate in the experimental group was higher compared to the control group; to some extent, this might suggest that AT was a more effective treatment compared to other treatments. Importantly, subgroup analysis (AT adjunctive to other treatments versus other treatments alone) also supported this result with OR of 2.84.Adverse effects were poorly reported in included studies. One study reported some minor adverse effects, and 5 studies reported no adverse effects. This might indicate the safety of AT for COPD patients.There were some limitations in this study. Firstly, methodological quality of the included studies was generally low. For example, most of the included studies had high risk of performance bias. Secondly, most analysis of the data in the meta-analysis indicated that there was heterogeneity. Thirdly, there were various intervention forms of AT, which might make it difficult to evaluate the efficacy of AT alone. Finally, some resources with language other than English and Chinese might not be included in this review.


## 5. Conclusions

AT may be effective and safe in improving functional effects and quality of life in COPD patients. Besides, AT may also improve pulmonary function of COPD patients. Evidences are inadequate to support the potential of AT in improving breathlessness of COPD patients. These evidences may be useful to clinicians, patients, and health policy-makers with regard to application of AT in COPD. However, further high-quality RCTs are needed to confirm the efficacy and safety of AT for COPD patients.



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*Source: 3026726-2018-05-20.xml*