Role of Acupuncture in the Treatment of COPD: An Overview of Systematic Reviews
Authors Chun L, Li X, Feng Z, Xie Y, Li J
Received 3 January 2021
Accepted for publication 12 February 2021
Published 25 March 2021 Volume 2021:14 Pages 1079—1092
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Scott Fraser
Liu Chun,1 Xuanlin Li,2 Zhenzhen Feng,2 Yang Xie,3 Jiansheng Li2,3
1Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200030, People’s Republic of China; 2Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 3Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China
Correspondence: Jiansheng Li
Henan University of Chinese Medicine, No. 156 Jinshui East Road, Zhengzhou, 450046, People’s Republic of China
Email [email protected]
Background: Since consistent evidence on the effectiveness of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD) is not available, this overview aims to summarize and critically evaluate the methodological and evidence quality of systematic reviews (SRs) on this topic.
Methods: Eight electronic databases were searched to identify relevant SRs of the use of acupuncture in the treatment of COPD from inception to January 2021. Two researchers independently screened the literature, extracted the data, and cross-checked the data. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) list was used to assess the methodological quality of SRs. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence for the outcomes of interest.
Results: Nine SRs that conducted quantitative syntheses were included in this overview. The methodological quality of the SRs and the quality of evidence for the main outcome measures were generally unsatisfactory. Only 2 SRs were rated as low methodological quality by AMSTAR 2, and the remaining SRs were rated as critically low quality. The key limitations of the SRs were lack of a protocol and registration or a list of excluded studies. We did not find high-quality evidence to confirm the effectiveness of acupuncture for COPD, and the main reason was that the qualitative data synthesis relied on trials with small sample sizes and critically low quality.
Conclusion: Acupuncture appears to be an effective therapeutic method for COPD, but the credibility of the results is limited owing to the generally low methodological quality and evidence quality of the included SRs. Further rigorous and comprehensive studies are required to provide robust evidence and draw definitive conclusions.
Keywords: acupuncture, chronic obstructive pulmonary disease, overview, AMSTAR 2, GRADE, systematic review
Chronic obstructive pulmonary disease (COPD), which is characterized by persistent airway inflammation and gradual progression of irreversible airway obstruction, is one of the top three causes of death worldwide.1 According to estimates, more than 5 million 400 thousand people will die of COPD or related diseases in the next 40 years, which carries heavy economic and social burdens.1–3 Drug therapy for COPD is long, costly and often associated with drug-related toxicity, therefore, Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline states that nonpharmacological treatment is complementary to pharmacological treatment and should form part of the comprehensive management of COPD.1,4 Pulmonary rehabilitation (PR) has been recommended as a beneficial nonpharmacological intervention for patients with COPD, but poor referral and uptake rates by suitable patients with COPD are global issues.5–7 Therefore, new nonpharmacological therapies are urgently needed to slow or even stop the progression of COPD.
Acupuncture is an important component of traditional Chinese medical (TCM) and an effective alternative therapy that is used to prevent and treat many diseases, including respiratory diseases.8–10 Proponents argue that acupuncture is effective at relieving symptoms and improving quality of life and activity endurance, and it is associated with fewer adverse effects than conventional approaches used to treat COPD.11 In recent years, with the increasing number of clinical studies12–14 on acupuncture treatment of COPD, a certain number of systematic reviews (SRs)15–23 have been published to provide corresponding evidence supporting clinical decision-making. However, based on preliminary studies, the results of different systematic evaluations are not completely consistent, which are unable to effectively guide clinical practice.
Meta-analysis is considered the highest scientific level for summarizing the results from different analyses. However, considering heterogeneity often exists in published SRs and the evidence from different SRs on the same topic was often conflicting, it has risks accepting the results of a single SR uncritically.24–26 An overview of SRs is required to overcome the limitations of individual SRs and provide comprehensive evidence. In this study, Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) and the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) system were applied to comprehensively evaluate the quality of the methodology and evidence of existing SRs, thus evaluating the applicability and safety of acupuncture and providing a basis for future high-quality research on acupuncture treatment of COPD.
Materials and Methods
Electronic literature searches were conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database (CNKI), WANFANG DATA, Chinese Biomedical Literature Database (CBM) and Chongqing VIP (CQVIP), all from inception to January 20, 2021. No restrictions were imposed on the source, publication date, or language of the SRs. The search terms and basic search strategy were as follows: (“COPD” OR “chronic obstructive pulmonary disease” OR “COAD” OR “chronic obstructive lung disease” OR “pulmonary disease, chronic obstructive”) AND (“acupuncture” OR “acupuncture therapy” OR “manual acupuncture” OR “electroacupuncture” OR “auricular acupuncture” OR “warm acupuncture” OR “acupoints”) AND (“systematic review” OR “meta-analysis” OR “systematic assessment”). Detailed search strategies are shown in Table S1. In addition, the references of relevant reviews were searched manually to ensure comprehensive data collection.
Inclusion and Exclusion Criteria
We included studies that met the following criteria:
- Study Design and Population: SRs were based on RCTs of acupuncture for COPD. The participants were diagnosed with COPD according to any internationally recognized clinical guidelines, and no restriction was placed on gender or the stage of COPD (stable or acute exacerbation).
- Interventions: Treatment measures in the intervention group included various invasive acupuncture therapies (needle acupuncture, electroacupuncture, auricular acupuncture, and body acupuncture, et al) or acupuncture combined with medication therapy, pulmonary rehabilitation, but studies using non-invasive techniques such as single moxibustion, acupressure, and point application were excluded. Treatments applied to the control group included comfort therapy (sham acupuncture or blank control) or other therapies (medication therapy or other nondrug therapies).
- Outcomes: At least one of the prespecified outcomes was reported: 1) exercise capacity: 6-minute walking distance (6MWD); 2) health-related quality of life: St. George’s Respiratory Questionnaire (SGRQ); 3) lung function: FEV1%pre, FEV1/FVC.
We excluded studies that met the following criteria:
- Studies that were published in abstract form with no full text.
- Non-RCT SRs, commentaries, guidelines, protocols, editorials and narrative reviews;
- Duplicated publications of the same SRs.
Literature Screening and Data Extraction
We searched the databases according to the predeveloped standardized search strategy. All retrieved literatures were imported into Endnote X8 software (Tomson Research Soft, Stanford, CT, USA). Two reviewers (LC and ZZF) independently screened for candidates according to the inclusion and exclusion criteria by reading the title and abstract. Then, the full texts were downloaded for further screening. At the same time, bibliographic references were also reviewed to identify possible SRs. The disagreements were resolved by discussion. If necessary, the discrepancies were resolved by consulting the third reviewer (YX).
The characteristics of SRs were extracted, including author, title, publication year, sample size, intervention, outcomes, quality assessment tool, and conclusions. Data were independently extracted by two reviewers (LC and ZZF) using Microsoft Excel, and two reviewers cross checked to eliminate mis-entry. Discrepancies were resolved by a discussion among the team members or arbitrated by the third reviewer (YX).
Two reviewers (LC and XLL) independently evaluated the quality of the included reviews by AMSTAR 2,24 an updated and improved version of the AMSTAR,27,28 which is available at https://amstar.ca/index.php. It contains 16 items, and seven items (items 2, 4, 7, 9, 11, 13, and 15) are critical domains. Moreover, AMSTAR 2 proposes a four-level scheme (high, moderate, low, and critically low) to rate the overall confidence of the included SRs, and each item was evaluated as “yes”, “partial yes” and “no”.
Strategy for Data Synthesis
We reported the results narratively in text and tables, together with comments on the quality of the evidence. We organized the data by intervention target and types of reported outcomes.
Grading of the Quality of Evidence
Two reviewers (LC and XLL) independently used the GRADE29 system to assess the quality of primary evidence. The following criteria were considered: risk of bias, inconsistencies, indirectness, inaccuracy, and publication bias. The quality of evidence for the outcomes was downgraded from four points initially to one point for each “not reported” or “serious” rating and to two points for each “very serious” rating. Then, meta-analyses were rated as “high” (4 points), “moderate” (3 points), “low” (2 points) or “very low” (≤ 1 point) quality of evidence. Any disagreements were resolved by consensus or discussion with the third reviewer (JSL). A descriptive analysis was used for the efficacy evaluation.
Literature Search and Selection
A total of 151 potentially related literature were retrieved from 8 databases. After 78 duplicated literatures were omitted, the titles and abstracts of 73 literatures were screened, and 52 literatures were excluded because they failed to meet the inclusion criteria. After downloading and reading the other 21 literatures, 12 literatures were excluded (The list of excluded studies with reasons for exclusion are presented in Table S2). Finally, we included 9 SRs.15–23 The process of the literature search and screen is shown in Figure 1.
Figure 1 Flowchart of literature selection.
Characteristics of the SRs
The characteristics of the 9 SRs included in our final analysis are summarized in Table 1. Five SRs16,17,21–23 were published in Chinese, and the other 415,18–20 were published in English. The number of RCTs included in these SRs varied widely, ranging from 7 to 27, and the total number of participants ranged from 326 to 1298. The interventions administered to the therapy groups are mainly acupuncture, acupuncture plus medication or acupuncture plus pulmonary rehabilitation; the interventions administered to the control groups were mainly medication, sham acupuncture, or pulmonary rehabilitation. The treatment duration ranged from one week to one year. All SRs evaluated the methodological quality of the original research; 8 SRs15–22 applied the Cochrane Handbook for Systematic Reviews of Interventions, and the other23 applied the Jadad scale.
Table 1 Characteristics of the Included Systematic Reviews
No SRs presented high and moderate levels of methodological quality based on the AMSTAR 2 scores; only 2 SRs18,19 scored at low overall levels, while the other 7 SRs15–17,20–23 scored at critically low levels (see Figure 2). The key factors affecting the methodological quality of the SRs were item 2 (only 2 SRs18,19 established a prior study protocol) and item 7 (none of the SRs explained the reasons for selecting the study type or provided a complete list of excluded studies with reasons). Seven SRs15–17,20–23 reported incomplete elements of the literature search strategy and did not describe the use of a specific search strategy. Four SRs15,17,22,23 used appropriate statistical methods to synthesize the results, but the sources of heterogeneity were not analysed. Three SRs16,17,23 did not consider the risk of bias of individual studies when interpreting and discussing the results. Three SRs16,20,22 did not investigate the possibility of publication bias or discuss the effect of publication bias on outcomes when quantitatively merging the results.
Effectiveness of Acupuncture and Evidence Quality
Since the obtained data were unable to be quantitatively analysed, a descriptive analysis method was adopted to evaluate the outcomes of interest in the SRs included in this study, and the GRADE system were assessed for each single outcome. Specific research results are presented in Table 2 and Figure 3.
Table 2 Quality of Evidence in Included Systematic Reviews with GRADE
A total of 5 SRs16–19,23 analysed the outcome of the 6MWD test: 1) Four SRs17–19,23 compared acupuncture plus medical treatment with medicine treatment. Among these articles, one SR19 conducted a subgroup analysis of patients with different clinical stages of COPD, showing a significant improvement only in patients with stable COPD (MD 33.05, 95% CI 19.11 to 46.99, low quality). Two SRs18,23 reported obvious improvements in the acupuncture group (MD 10.16, 95% CI 4.34 to 15.99, low quality; MD 35.15, 95% CI 2.73 to 67.92, low quality); one SR17 showed a nonsignificant improvement (MD 14.71, 95% CI −17.09 to 6.50, moderate quality). 2) Three SRs16,18,19 compared acupuncture with sham acupuncture and showed a significant improvement in the 6MWD of in the acupuncture group (MD 63.05, 95% CI 39.27 to 86.83, low quality; MD 33.69, 95% CI 5.58 to 61.52, low quality; MD 76.68, 95% CI 39.93 to 113.43, moderate quality). 3) When comparing acupuncture plus pulmonary rehabilitation with pulmonary rehabilitation,20 statistically significant differences were not observed between the groups (MD 8.40, 95% CI −5.88 to 22.68, low quality). The evidence mapping of 6MWD is shown in Figure 3A.
A total of 4 SRs16,18,20,23 analysed SGRQ (Figure 3B): 1) One SR23 compared acupuncture plus medicine treatment with medicine treatment, and no significant difference was detected between the two groups (MD −2.76, 95% CI −5.65 to 0.14, low quality). 2) Two SRs16,18 compared acupuncture with sham acupuncture: 1 SR16 indicated a statistically significant difference between the two groups (MD −9.00, 95% CI −14.44 to −3.56, moderate quality); the other18 showed an improvement that was not statistically significant in the two groups (MD −10.66, 95% CI −22.24 to 0.92, moderate quality). 3) A significant difference in SGRQ was not observed between acupuncture and pulmonary rehabilitation group and the pulmonary rehabilitation group (MD 0.3, 95% CI −6.83 to 7.43, very low quality).
Eight SRs15–17,19–23 were conducted to systematically analyse the outcome of FEV1%pre (Figure 3C): 1) Seven SRs15,17,19–23 compared acupuncture plus medicine treatment with medicine treatment. Two SRs15,19 conducted a subgroup analysis of patients with different clinical stages of COPD; one review15 reported that acupuncture significantly improved FEV1%pre only in patients with acute exacerbations of COPD (MD 3.09, 95% CI 1.00 to 5.18, low quality); another review19 reported no significant difference in either patients with stable or acute exacerbations of COPD between the two groups. Four17,20,21,23 of the 5 SRs without a staging analysis showed that the change in FEV1%pre between interventions was statistically significant (MD 4.94, 95% CI 1.75 to 8.11, very low quality; MD 5.93, 95% CI 5.73 to 6.14, very low quality; MD 1.98, 95% CI 0.14 to 3.82, moderate quality; MD 1.98, 95% CI 0.26 to 3.70, very low quality); one SR22 showed no significant difference in FEV1%pre between the two groups (MD 0.10, 95% CI −0.62 to 0.82, low quality). 2) Two SRs16,19 compared acupuncture with sham acupuncture. The improvement in FEV1%pre in the acupuncture group was more significant than in the control group (MD 4.93, 95% CI 1.87 to 7.99, moderate quality; MD 5.40, 95% CI 2.90 to 7.91, moderate quality). 3) One SR20 compared acupuncture plus pulmonary rehabilitation with pulmonary rehabilitation, and more obvious improvements were noted in the acupuncture group than in the control group (MD 7.80, 95% CI 6.91 to 8.68, very low quality).
A total of 7 SRs16,17,19–23 analysed the outcome of FEV1/FVC (Figure 3D): 1) Six SRs17,19–23 compared acupuncture plus medicine treatment with medicine treatment. One SR19 reported that acupuncture significantly improved FEV1/FVC only in patients with acute exacerbations of COPD (MD 3.42, 95% CI 1.55 to 5.29, very low quality); Three17,21,23 of the 5 SRs without a staging analysis showed greater improvements in FEV1/FVC in the acupuncture group than in the control group (MD 4.40, 95% CI 0.72 to 8.08, moderate quality; MD 10.16, 95% CI 4.34 to 15.99, moderate quality; MD 0.47, 95% CI 0.27 to 0.67, very low quality), two SRs20,22 showed no significant difference between the two groups (SMD −0.13, 95% CI −0.37 to 0.12, low quality; MD 1.56, 95% CI −0.18 to 3.29, very low quality). 2) Two SRs16,19 compared acupuncture with sham acupuncture and revealed a significant difference between the two groups (MD 7.57, 95% CI 0.34 to 14.80, very low quality; MD 6.64, 95% CI 3.44 to 9.83, moderate quality). 3) One SR20 compared acupuncture plus pulmonary rehabilitation with pulmonary rehabilitation, but did not observe a significant difference between the two groups (MD −3.50, 95% CI −10.11 to 3.12, very low quality).
Safety and Adverse Events
Of all 9 SRs, adverse effects were mentioned in 8 SRs.15,16,18–23 Of these 8 SRs, 5 SRs15,16,19,20,22 stated that no adverse events were reported in the studies they included; 2 SRs18,23 reported mild adverse reactions but did not describe them in detail; and the remaining SR21 reported that the adverse events caused by acupuncture included subcutaneous haemorrhage, pinprick pain sensations, and an inability to tolerate stimulation. However, a meta-analysis was unable to be conducted due to insufficient data.
Overview of SRs is an increasingly popular form of evidence synthesis, and that provides more authentic and reliable evidence for clinical decision-making.30 Previous researches have shown that acupuncture is an effective in the treatment of for COPD.8,13,14 This overview provided a comprehensive mapping of the evidence on the effectiveness of acupuncture for COPD. A total of 9 SRs were included in this overview, the evaluation with AMSTAR 2 showed that the quality of included SRs was low or critically low and the results of the GRADE system evaluation showed that the strength of evidence was very low to low for most outcomes.
Assessment of the Quality of the Included SRs
AMSTAR 2 was used to evaluate the methodological quality of the included SRs. The overall methodological quality of the 9 SRs included in this study was “low” and “critically low”. Specifically, in our study, SRs frequently lacked details on the prior registration and/or publication of protocol, failed to provide of list of excluded studies at full-text level or did not assess the potential effect of the risk of bias on the results. The proportion of reviews with protocol registration in our study was 22%. The Preferred Reporting Items for SRs and Meta-analyses (PRISMA) statement first proposed registry for the protocol of SRs, and it notes that prospective registrations of SRs might reduce the probability of bias in the review and improve the transparency of the research since the authors report their methods and statistical analysis a priori.31 According to the assessment performed in this study, none of the 9 SRs met item 7. The list of excluded studies and the reason for the exclusion must be explained since the effect of the excluded studies on a systematic literature review cannot be determined if the list of excluded studies and reasons for exclusion are not provided at the same time.24 Although all SRs used appropriate methods for the risk of bias assessment, only some SRs considered the effect of the quality of included trials on their results. SR researchers should be aware that simply assessing the risk of bias is not sufficient, and its effect on the results of the review should be assessed. Considering the critically low quality of all the included SRs, the results should be interpreted with caution.
Overall Completeness and Applicability of the Evidence
The 6MWD and SGRQ were used as indexes to evaluate the exercise capacity and quality of life of patients with COPD.32,33 FEV1%pre and FEV1/FVC were recommended to determine the diagnosis and prognosis of COPD.34,35 In the present study, we analysed these four outcomes of interest in 3 subgroups divided according to different intervention measures. The results revealed inconsistent results from diverse subgroups. In the subgroup of acupuncture compared with sham acupuncture, all correlation studies showed that intervention groups presented a significantly improved in 6MWD, FEV1%pre and FEV1/FVC, half of studies exhibited statistically significant improvement in SGRQ. Notably, the majority of these results also have clinical implications, although the minimal clinically important difference (MCID) was also considered.36,37 However, unifying conclusions cannot be drawn from the equivocal results of the remaining 2 subgroups (acupuncture plus medicine treatment compared with medicine treatment, and acupuncture plus pulmonary rehabilitation compared with pulmonary rehabilitation). We speculated that the reason for this phenomenon is the differences in the acupoints, acupuncture occasion, acupuncture manipulation, and stimulation volume.
In our study, the overall quality of the evidence supporting the outcome indicators was mainly “low” and “very low”, and no evidence was considered “high”. Based on our study, we identified possible reasons for the inconsistency of research results and the reduction in the evidence level, as described below. 1) Poor methodological quality of the included RCTs. Most of the trials mentioned grouping using randomization methods but did not describe specific methods. Additionally, considering the operando visualization of acupuncture, it is very difficult to conduct blinded methods. 2) High heterogeneity existed among some studies. The sources of heterogeneity were derived from differences in acupuncture types and the frequency and duration of treatment. 3) The quality of the evidence was downgraded due to the wide confidence interval or the sample size that did not meet the optimal information size.
Implications for Future Practice and Research
Because of its superior availability and relatively low clinical side effects, acupuncture has become an important complementary and alternative therapy for numerous diseases.38,39 We found some positive evidence supporting the use of acupuncture in the treatment of COPD, although the GRADE quality of evidence was assessed as low. Due to these concerns, more rigorous larger-scale and well-designed RCTs are needed to provide higher quality evidence and evaluate the efficacy of acupuncture for COPD. First, RCTs should follow the corresponding guidelines such as CONSORT40 (Consolidated Standards of Reporting Trials) which applied to all kinds of RCTs or the characteristic guidelines such as STRICTA41 (Standards for Reporting Interventions in Controlled Trials of Acupuncture) for acupuncture. Second, many different types of acupuncture are used to treat COPD in clinical practice. Therefore, future studies comparing different acupuncture interventions are needed to identify the most effective acupuncture method. Furthermore, the optimal duration and frequency of treatment are also important for patients with COPD. Third, all SRs must be registered in advance to facilitate processing transparency and to avoid the risk of bias in methodology. Additionally, crucial safety evaluations of acupuncture in the treatment of COPD are needed in clinical trials, and cost-effectiveness studies should be performed to evaluate acupuncture as a treatment for COPD. This approach will provide a comprehensive assessment of the effectiveness and safety of acupuncture for COPD.
Several limitations need to be taken into account when interpreting our results. First, we only searched Chinese and English databases, and thus SRs published in other languages that met the inclusion criteria may have been missed. Second, the evaluation process of AMSTAR 2 and GRADE is inevitably subjective and may lead to bias, though this study had been independently evaluated and checked by two researchers. Third, we only narrative summarized rather than quantitatively analysed the effectiveness of interventions because of obvious clinical and statistical heterogeneity between the included systematic reviews, as well as complex categories of interventions. Lastly, since the number of analysed articles was limited, we were unable to include factors such as the different types of acupuncture and stages of COPD in subgroup analyses.
What is the precise role of acupuncture in the treatment of COPD? In our study, the methodological quality of the included SRs varied, the quality of evidence underlying these outcomes was mixed (very low to moderate), and the firm conclusions on this question are difficult to draw. Therefore, while constantly improving the experimental design, researchers should combine the characteristics of acupuncture diagnosis and treatment with modern clinical RCTs to produce more high-quality, scientific and accurate clinical evidence.
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
This research was supported by grants from the Program of National Natural Science Foundation of China (No. 81830116); the Qihuang Scholars Award of the State TCM Academic Leader Program (No.(2018)284); National Key Research & Development Program of China (No. 2018YFC1704800, 2018YFC1704802); Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 19HASTIT008).
The authors report no conflicts of interest in this work.
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