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; = 3.83, ) and effective rate was higher (OR: 2.26; 95% CI: 1.43 to 3.58; = 3.48, ) in the experimental group compared to the control group. Symptom domain scores (MD: −24.86; 95% CI: −32.17 to −17.55; = 6.66, ), activity domain scores (MD: −16.52; 95% CI: −22.57 to −10.47; = 5.36, ) and impact domain scores (MD: −13.07; 95% CI: −17.23 to −8.92; = 6.16, ) 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; = 6.01, ) 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.

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 [35]. 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 test to estimate heterogeneity of both the MD and OR. Further analysis was performed using the I2 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 when I2 was greater than 50% or a low value () was reported for the 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 (), (ii) not targeted comparators (), (iii) not targeted outcomes (), and (iv) full-text articles unavailable (). Thus, nineteen studies (1298 participants) finally met our criteria and were included in this review [725]. The study selection process was outlined in Figure 1.

3.2. Data Extraction and Assessment of Risk of Bias

A detailed description of the characteristics of included studies was outlined in Table 1. We determined the Cochrane “risk of bias” score for each study and this information was summarized in Table 2 and Figures 2 and 3.

3.3. Effects of Interventions
3.3.1. 6MWD

Eight studies [9, 10, 1618, 21, 23, 25] provided numerical data for 6MWD and were included in the meta-analysis. Analysis of the data indicated that there was heterogeneity ( = 65.96, ; = 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; = 3.83, ) (Figure 4).

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 ( = 39.18, ; = 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; = 1.95, ) (Figure 5).

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 ( = 0.05, ; = 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; = 6.66, ) (Figure 6).

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 ( = 0.04, ; = 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; = 5.36, ) (Figure 7).

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 ( = 0.00, ; = 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; = 6.16, ) (Figure 8).

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 ( = 30.40, ; = 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; = 1.44, ) (Figure 9).

3.3.4. Effective Rate

Ten studies [7, 1216, 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 ( = 8.33, ; = 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; = 3.48, ) (Figure 10).

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 − and −, respectively. There was significant difference reported within AT plus PR group ().

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 Table 3). 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].

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 ( = 9.17, ; = 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; = 5.20, ) (Figure 11).

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 ( = 22.16, ; = 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; = 1.80, ) (Figure 12).

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 and −, respectively. However, the 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 ( = 32.35, ; = 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; = 2.10, ) (Figure 13).

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 (), both AT plus PR group and PR group demonstrated a significant change for SGRQ total scores (−, ; −, ). 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 ( = 0.00, = 1.00; = 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; = 6.01, ) (Figure 14).

3.7.4. Effective Rate

Seven studies [7, 1316, 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 ( = 2.38, ; = 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; = 3.53, ) (Figure 15).

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.

Additional Points

Registration Number. This article is registered with PROSPERO 2016 CRD42016054335 (available from http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016054335).

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Authors’ Contributions

Jiajia Wang searched the literature, conducted the statistical analysis, and drafted the manuscript. Yang Xie and Xueqing Yu screened the studies, extracted the data, and evaluated the risk of bias. Jiansheng Li revised the manuscript. Yang Xie conceived this study.

Acknowledgments

This study was supported by Henan Province Priority and Advantage Discipline Construction Engineering Projects-Traditional Chinese Medicine (no. STS-ZYX-2017003).

Supplementary Materials

The methods for this study had been developed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. (Supplementary Materials)