Chronic obstructive pulmonary disease (COPD) is a common, slowly progressing disease characterized by irreversible airflow limitation and the gradual loss of lung function. It is thought that COPD affects 64 million people worldwide, and World Health Organization projections estimate that it will be the third leading cause of death by 2030.[1–2] COPD brings a significant burden not only for patients and their families but also for social healthcare systems in general. The disease is associated with poor health-related quality of life in many patients.
Smoking cessation is considered as number one priority, followed by pharmacological intervention, to help relieve symptoms, reduce acute exacerbations, and improve exercise capacity and quality of life in clinically stable COPD patients. However, more effective and safer therapies are still looked for.
Acupuncture therapy has been widely used to treat a variety of conditions, such as stroke,[5–8] insomnia, migraine,[10,11] knee pain,[12–14] neck pain,[15,16] frozen shoulder, pressure ulcer,[18,19] irritable bowel syndrome, chronic pelvic pain syndrome, cancer care, Alzheimer disease, and COPD.[24–26] Specifically, acupuncture therapy has been suggested and used to treat patients with COPD in China.[24,25]
It is reported that acupuncture may help relieve COPD by reducing bronchial immune-mediated inflammation and by promoting release of vascular and immunomodulatory factors.[27,28] A recent systematic review of randomized controlled trials of acupuncture therapies for treating COPD found that acupuncture therapies may result in clinically important improvements in quality of life and dyspnea. However, research studies have generally provided poor evidence due to methodological limitations, including low-quality study design, inadequate control groups, and variation in acupuncture composition. Therefore, more rigorously designed studies are needed to elucidate the effectiveness of acupuncture therapy for treating patients with COPD. We hypothesized that real acupuncture would be superior at 8 weeks compared with sham needle acupuncture. Thus, this study aimed to conduct a multicenter, randomized, sham-controlled trial to evaluate the efficacy of acupuncture therapy for treating patients with COPD.
2.1 Study design
This is a two-arm, parallel group study with participants, assessor, and analyst blinding. The study was conducted at Hangzhou Fuyang Hospital of Traditional Chinese Medicine, The People's Hospital of Fuyang, and the First Affiliated Hospital of Heilongjiang University of Chinese Medicine in accordance with the Declaration of Helsinki and its amendments and each institution's Guidelines for Good Clinical Practice. From April 2014 to July 2015, 72 eligible participants were randomly divided into 2 groups (real acupuncture group and sham acupuncture group) at a 1:1 allocation ratio. The patients received either real or sham acupuncture needling 3 times weekly for 8 weeks. Outcome evaluation and data analysis were performed after 8 weeks of treatment by a team of professionals, who were blinded to group allocation.
2.2.1 Inclusion criteria
The inclusion criteria were as follows:
- A confirmed diagnosis of COPD (stage II, III or IV) in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines
- A clinically stable condition without history of infections or exacerbation of respiratory symptoms
- No changes in medication within the 3 months preceding the study outset
- No signs of edema
- The ability to walk without assistance
- No pulmonary rehabilitation in the previous 6 months
- The provision of written informed consent prior to enrollment into the study
2.2.2 Exclusion criteria
Patients with the following conditions were excluded: cardiovascular disease, collagen disease, renal failure, thyroid dysfunction, hepatic function disorder, cancer, and severe mental disorder.
2.3 Randomization and allocation concealment
Participants who met all the inclusion and exclusion criteria were randomly assigned to the real acupuncture group or sham acupuncture group in a 1:1 ratio at the second visit through central randomization. A professional statistician, who was blinded to this study, generated the random numbers using a computerized number generator with SAS package (Version 9.1; SAS Institute Inc., Cary, NC). Allocation was concealed in sequentially numbered, opaque, and sealed envelopes containing the randomization assignments. Acupuncturists were not blinded. However, the participants, outcome assessors, and data analysts were masked to the treatment allocation.
In addition to the daily medication, the participants in the real acupuncture group received 30-minute sessions of acupuncture treatment, 3 times weekly for 8 weeks. Acupoints were selected according to the previous studies on acupuncture for COPD and the literature describing the traditional prescription of acupuncture points for bronchial asthma and chronic bronchitis pulmonary dysfunction.[30,31] The following bilateral acupoints were used: LU1, LU9, LI18, ST36, GB12, BL13, BL20, and BL23. Both groups used the same acupoints.
Sham acupuncture treatment was operated by a Park sham device. The tips of the sham needles were blunt and appeared to be penetrating the skin but actually telescoped back into place in the sham acupuncture group. The needles were not inserted into the skin.
Both real and sham needles were the same size (sterile disposable acupuncture needles, 40 mm in length and 0.30 mm in diameter; Andy brand, Guizhou Andy Medical Instrument Co., Guizhou, China). De qi (tingling, numbness, and heaviness) was achieved during the manipulation of needles at every point in the real acupuncture group.
2.5 Outcome measurements
All outcomes were measured at baseline and after 8 weeks of treatment.
2.5.1 Primary outcomes
The primary outcome was the severity of dyspnea on exertion (DOE), which was assessed using the 6-minute walk test (6MWT). A modified 10-point Borg category ratio scale was used to measure the breathlessness before and immediately after the 6MWT, where 0 signified “breathing very well, barely breathless” and 10 signified “severely breathless.”
2.5.2 Secondary outcomes
Secondary outcome measures included the 6-minute walk distance (6MWD); the lowest oxygen saturation during the 6MWT; and forced expiratory volume in 1 second (FEV1). In addition, quality of life of the patients was measured with the St. George Respiratory Questionnaire (SGRQ). Measurements were obtained at baseline and after 8 weeks of treatment.
2.6 Statistical analysis
Statistical analysis was conducted by an analyst. Statistical Package for the Social Sciences (SPSS) software 17.0 (SPSS Inc., Chicago, IL) was used to conduct the data analysis. The sample size was calculated based on the primary outcome, that is, the change in the Borg scale score at the end of the 6MWT. The minimal clinically important difference in the Borg scale score in COPD patients is 2 units. Therefore, the required sample size of this study was estimated to be 72 subjects (36 per group) in order to detect a minimal difference between means in the Borg scale score of 2.0 with α = 0.5 and β = 0.8. We also assumed a 20% dropout rate. All data are presented as the mean (standard deviation [SD]) or the mean (95% confidence interval [CI]). Analysis was by intention-to-treat. Statistical significance is reported as P values from independent t-tests, because all outcome data were normal distribution. The statistical significance level was set at P < 0.05.
A total of 153 Chinese participants were initially screened and entered the study (Fig. 1). Of these 153 patients, 52 did not meet the study criteria and 29 declined to participate. Therefore, 72 participants were randomized into the real acupuncture and sham acupuncture groups. All 72 subjects were evaluated using the 6MWT, but only 65 patients completed the treatment. Seven patients withdrew from the study. The major reasons for withdrawal were withdrawal of consent and change of medication (Fig. 1).
The patient characteristics and the baseline symptom severity of the study population are summarized in Table 1. The 2 groups did not differ significantly in all the characteristics and clinical variables at the baseline visit. At baseline, the mean age (SD) was 67.8 (5.4) years in the real acupuncture group and 67.1 (6.1) years in the sham acupuncture group. The body mass index (BMI) was 23.8 (4.5) in the real acupuncture group and 23.6 (4.3) in the sham acupuncture group. The baseline 6MWT post-Borg scale score, 6MWD, and oxygen saturation as measured by pulse oximetry (SpO2) were 4.4 (2.1), 417.3 (122.5), and 87.6 (6.4), respectively, in the real acupuncture group and 5.1 (2.3), 394.8 (131.6), and 88.5 (6.7), respectively, in the sham acupuncture group. In addition, the baseline forced vital capacity (FVC) and FEV1 were 2.9 (0.7) and 47.3 (17.1) in the real acupuncture group and 2.7 (0.7) and 43.9 (16.8) in the sham acupuncture group.
We examined the mean change from baseline (95% CI) by treatment and the difference (95% CI) between real acupuncture and sham acupuncture to evaluate the efficacy of real acupuncture for treating COPD. The results for the efficacy endpoints after 8 weeks of treatment are summarized in Table 2. Real acupuncture improved the severity of DOE evaluated by the 6MWT as well as the lung function compared with sham acupuncture at 8 weeks. After 8 weeks, the real acupuncture group exhibited significant improvements in health-related life quality compared with the sham acupuncture group (Table 2).
The results of this study met our hypothesis that real acupuncture was superior at 8 weeks compared with sham needle acupuncture for treating COPD. Previous studies have assessed the efficacy of acupuncture for treating COPD. However, 2 studies were conducted in the United Kingdom, and the included patients had various diseases, including bronchial asthma, interstitial pneumonia, cystic fibrosis, and COPD.[38,39] It is therefore inconclusive whether acupuncture is really effective for treating COPD alone. One study was conducted in Japan. It found that acupuncture was effective for treating Japanese patients with COPD. In addition, although 4 studies were also conducted to evaluate the efficacy of acupuncture for treating COPD in China, all these studies suffered from methodological design limitations.[24,25,40,41]
To our best knowledge, this study is the first multicenter, randomized, sham-controlled trial with concealed allocation, and participant, assessor, and analyst blinding conducted in China. Our findings demonstrated the efficacy of acupuncture therapy for patients with COPD.
In this study, the mean decrease of the Borg scale score after the 6MWT, and the increase in the 6MWD with acupuncture treatment were significantly greater in the real acupuncture group than in the sham acupuncture group. In addition, the increase in lowest oxygen saturation during the 6MWT after acupuncture treatment was also greater in the real acupuncture group than in the sham acupuncture group. These results indicate the efficacy of acupuncture for treating the symptoms of COPD patients, especially DOE. Furthermore, the total score on the SGRQ was significantly decreased in COPD patients in the real acupuncture group, when compared with the patients in the sham acupuncture group. Thus, acupuncture treatment appears to be promising for improving the health-related quality of life of COPD patients.
This study had several limitations. First, it was impossible to interrupt the standard medication for the patients with COPD, so most patients kept taking their daily medication. Although the baseline medication was similar between the 2 groups, the achieved efficacy may have been the result of the synergistic effect of acupuncture plus medication, and not of acupuncture alone. Second, this study did not include a follow-up evaluation owing to its short duration. Thus, the long-term effect of acupuncture on COPD still needs to be addressed in the future. Finally, this study did not blind the acupuncturists, because it is impossible and hard to blind them. Therefore, their attitude might have also influenced the results of this study.
In conclusion, the results of this study found that acupuncture can improve DOE and health-related quality of life of COPD patients. Long-term randomized, controlled trials with follow-up assessments are needed to confirm our results.
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