Acupuncture for attenuating dyspnea in patients with chronic obstructive pulmonary disease

1 Division of Critical Care & Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan

2 Department of Chinese Medicine, China Medical University Hospital, Taichung, 40402, Taiwan

3 Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan

4 Acupuncture Research Center, China Medical University, Taichung, 40402, Taiwan

* Corresponding author Email: clhsieh@mail.cmuh.org.tw

Introduction

Chronic obstructive pulmonary disease (COPD) is an increasingly serious global health problem that is associated with significant morbidity and mortality. The main pathological feature of COPD is the persistent limitation of respiratory airflow, which leads to fatigue, dyspnea and decreased physical activity. Dyspnea is a cardinal symptom of COPD and increases in severity as the course of COPD progresses. Therefore, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommended in 2011 that COPD assessment should be based on the combination of symptoms, lung function and the risk of exacerbations. Acupuncture has become a popular treatment for various medical conditions. Whether acupuncture can improve lung function and exercise capacity in COPD patients by attenuating the dyspnea and fatigue associated with COPD is unclear. In our review, we discuss the latest assessment criteria for COPD according to the revised GOLD guidelines and summarise the most common outcome measures used to assess COPD patients. We also discuss the results of clinical trials of acupuncture treatment for COPD. The concept of the minimal clinically important difference score of outcome measures in COPD is also addressed.

Conclusion

COPD is a heterogeneous, multi-component disease that is associated with significant clinical burden and increasing mortality. Dyspnea is a common symptom. Pulmonary rehabilitation and acupuncture are effective methods of treatment in COPD patients. We call for further studies into acupuncture as a treatment method to further our understanding.

Chronic obstructive pulmonary disease (COPD) can be caused by cigarette smoking or exposure to noxious inhalants. COPD has become an increasingly serious worldwide health problem that is associated with significant morbidity and mortality^[1]. It is estimated that COPD will be the third leading cause of death worldwide and the fifth leading contributor to global disease burden by 2020^[1]. The main pathological feature of COPD is persistent restricted respiratory airflow caused by chronic airway inflammation, which leads to decreased physical activity, fatigue and dyspnea^[2].

The previous guidelines for the assessment of COPD severity and treatment suggested lung function testing, especially the measurement of the one-second forced expiratory volume (FEV1). Dyspnea, the subjective sensation of difficulty during breathing, is a cardinal symptom of COPD, and its severity and magnitude increase as COPD progresses^[3]. Therefore, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) revised the assessment criteria for COPD in 2011, recommending that COPD patients should be assessed based on a combination of symptoms, lung function and the risk of exacerbation^[4].

Pulmonary rehabilitation (PR) is suggested as a non-pharmacological treatment for COPD patients to improve their exercise tolerance and decrease the dyspnea and fatigue^[4]. However, whether acupuncture may be an effective non-pharmacologic treatment in COPD to attenuate dyspnea and fatigue, improve lung function and increase exercise capacity, is uncertain. In this review, we have introduced the recently revised GOLD guidelines for the assessment of COPD and summarised the most common outcome measures used in COPD. We have also analysed the results of recent clinical trials of acupuncture treatment for COPD.

Overview of the GOLD-2011 guidelines for COPD assessment

Since 2001, the GOLD has published its recommendations for the clinical diagnosis and management of COPD. The latest GOLD guidelines were announced in 2011, and emphasise that the assessment of COPD should include the evaluation of the combined symptoms that include the severity of respiratory airflow limitations, history of exacerbations and comorbidities^[4,5]. In contrast to previous recommendations, the new GOLD guidelines place less emphasis on spirometry testing for the evaluation of disease severity than on the evaluation of symptoms. The absolute level of FEV1 is no longer considered to be the only tool for severity classification in COPD, based on its lack of reliability as a marker for the severity of dyspnea, exercise limitation and health status impairment^[2,6].

For symptom assessment, several validated questionnaires have been used to distinguish patients with severe symptoms from those with less severe symptoms. The GOLD now recommends that the modified British Medical Research Council (mMRC) questionnaire or the COPD assessment test (CAT) be used to assess dyspnea in COPD^[4]. In addition, the new GOLD guidelines recommend that all COPD patients should first be assessed using the mMRC or CAT scale, with an mMRC grade of >2 or a CAT score of ≥10 as the definition of severe symptoms. Subsequent assessment of exacerbation risk is suggested to include both spirometry testing and the analysis exacerbation history, with GOLD 3 or 4 spirometry classification and two or more exacerbations during the preceding year, each representing high risk^[5]. Thus, according to the GOLD-2011 guidelines, the severity of COPD can be classified as category A, B, C or D (Figure 1).

Figure 1: COPD assessment based on the severity of symptoms, spirometry and the risk of exacerbations. Based on the recommendations of the GOLD-2011 guidelines, patients with COPD should be evaluated using a two-step assessment. Patients should first be assessed using the mMRC or the CAT. Patients with less symptoms, such as mMRC grade 0–1 or CAT<10, are assigned to the left side of the box, whereas patients with more symptoms (mMRC>2 or CAT≥10) are assigned to the right side of the box. The exacerbation risk of patients should be subsequently classified as low-risk (lower area of the box) or high-risk (upper area of the box), based on spirometry results (GOLD 1–2 = low risk, GOLD 3–4 = high risk) and exacerbations history during the previous 12 months (0–1 = low risk, ≥2 = high risk). Thus, the severity of COPD can be classified as category A, B, C or D. CAT, chronic obstructive pulmonary disease assessment test; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified British Medical Research Council questionnaire.

Outcome measures and the minimal clinically important difference score

COPD requires a multifaceted approach to clinical assessment and treatment. The most common methods for assessing COPD progression rely on lung function testing, with an emphasis on FEV1. However, current trends in clinical practice focus on the evaluation of clinical outcomes and patient-reported measures, such as dyspnea, exercise capacity, exacerbations, level of physical activity and health status, as essential parts of the clinical assessment of COPD beyond FEV1 measurements^[7,8,9]. The outcomes that have been most frequently applied to the assessment and treatment of COPD, including pulmonary rehabilitation, are summarised in Table 1.

Table 1 Outcome measures applied in COPD.

The outcome measures are further classified into dyspnea scales, quality of life scales, exercise capacity scales, pulmonary function test score and a multidimensional score^[7,8,9]. Because dyspnea is the most common COPD-related presentation, several different approaches have been used for measuring dyspnea in clinical trials, among which the Medical Research Council scale (MRCS), modified Borg scale (MBS), shortness of breath questionnaire, baseline dyspnea index and transition dyspnea index are most often used. For quality of life measures, the scales most commonly applied are the St. George respiratory questionnaire (SGRQ), chronic respiratory disease questionnaire, medical outcomes study short form-36 and frequency of exacerbations.

The methods most often used for assessing exercise capacity following treatment for COPD patients were the 6-minute walk test (6MWT), incremental shuttle walk test, endurance shuttle walk test and ergometry (usually bicycle-ergometer or treadmill). Pulmonary function tests, including measurements of the FEV1, functional residual capacity, inspiratory capacity, residual volume and total lung capacity have been frequently applied. Currently, multidimensional scoring, such as that based on the BODE (body mass index, degree of airflow obstruction, dyspnea and exercise capacity) index^[10] and the CAT^[7] are thought to be important prognosticators for COPD patients.

We suggest that acupuncture clinical trials that evaluate the treatment effect as the endpoint should use a standard set of outcome measures (Table 1). In addition, we suggest that the outcome measures should be quantified based on the minimal clinically important difference score (MCID). The MCID was developed by Jaeschke et al. in 1989 to improve assessments in which instrument-based measurements of outcomes that show statistically significant changes after intervention are not accompanied by significant changes in clinical parameters^[11]. A summary of the MCIDs of standard outcome measures is shown in Table 1.

The clinical trials of acupuncture in COPD

In our survey of the literature for studies of acupuncture treatments for COPD, we used the keywords ‘acupuncture and COPD’ to search for clinical trials in the PubMed database. All potentially relevant full-text articles in English that used dyspnea or breathlessness as an endpoint were included in our critical review. We reviewed nine clinical trials (Table 2), including one descriptive study trial and eight randomised controlled trials (RCTs)^{[12,13,14,15,16,17,18,19,20]}. Two of the RCTs used transcutaneous electrical nerve stimulation over acupoints (Acu-TENS) and the remaining seven trials used standard acupuncture for COPD patients. The outcome measures that were used included the reduction of dyspnea or the improvement of lung function. In six of the nine trials, positive results were observed following the acupuncture treatments^{[12,13,17,20]}, with the two studies of Acu-TENS treatment reporting improvements in both dyspnea and lung function in stable COPD patients^[15,18].

Table 2 Experimental design of clinical trials using acupuncture for dyspnea for COPD.

Detailed information regarding the study design, patient selection and outcome measures of the clinical trials of acupuncture treatments for COPD are listed in Table 2. Jobst et al. used a three-week randomised controlled study to investigate whether acupuncture provided benefits based on subjective scores of dyspnea following the 6MWT^[20]. Twenty-six COPD patients were enrolled in the acupuncture and control groups. The four subjective scores derived from the outcome measures were the general wellbeing, shortness-of-breath, oxygen cost and modified Borg scores. The 6MWT and lung function testing, including the peak expiratory flow rate, FEV1 and forced vital capacity measurements, were conducted.

The Jobst et al.^[20] study showed that the acupuncture group had significantly greater improvement in the 6MWT results and all of the subjective scores, compared with the control group. After three weeks of treatment, the mean distance of the 6MWT for the acupuncture group was 49.6 m greater than that of the control group. However, the results of lung function tests conducted before and after treatment showed no change in both groups. Jobst et al.^[20] proposed that their results demonstrated significantly greater improvement in dyspnea in the COPD patients who received the acupuncture treatment.

During the past five years, the Suzuki group has conducted three RCTs of acupuncture treatment for COPD^[12,13,17]. The major acupuncture points treated in the Suzuki group’s studies were the LU1 (Zhongfu), LU9 (Taiyuan), LI18 (Futu), CV4 (Guanyuan), CV12 (Zhongwan), ST36 (Zusanli), KI3 (Taixi), GB12 (Wangu), BL13 (Feishu), BL20 (Pishu) and BL23 (Shenshu; Table 2). They determined the efficacy of acupuncture treatment in stable COPD patients for improving dyspnea following exercise, using the Borg scale following the 6MWT; the lung function tests and the SGRQ were also conducted. The Borg scale results showed mean improvements of 2.2 points^[17], 2.0 points^[12] and 3.6 points^[13] in the acupuncture treatment groups. They also reported improvements in the FEV1 measurements, SGRQ scores and 6MWT distances. The results of the Suzuki group’s RCTs are summarised in Table 2.

Critical appraisal of the validity of acupuncture in COPD based on the MCID

The results of studies that assessed outcomes based on the MCID are summarised in Table 3. The two RCTs in which acupuncture treatment did not improve dyspnea used the visual analogue scale to quantify the outcome^[16,19], whereas the Suzuki group’s studies used more objective methods to measure the outcome beyond the FEV1, including the MBS, MRCS, SGRQ and 6MWT^[12,13,17]. The parameters that exhibited the greatest significant differences following treatment were the MBS, SGRQ and 6MWT, all of which contributed to the significant changes observed in the MCID scores. However, the changes in the MRCS and the FEV1 following treatment were of borderline significance based on the MCID score. Thus, investigators should evaluate the data from clinical trials based on both the p value and the MCID score.

Table 3 Analysis of the clinical significance of acupuncture in COPD trials by the definition of MCID.

COPD is a heterogeneous, multi-component disease associated with significant clinical burden and increasing mortality. Dyspnea is a very common symptom in COPD because of the persistent airflow limitations caused by the chronic airway inflammation. In addition to PR, a growing body of evidence suggests that acupuncture may be an effective non-pharmacologic treatment for attenuating dyspnea in COPD patients. We suggest that studies of the efficacy of acupuncture in COPD should use a standard set of subjective scales to obtain comparable evaluations of the clinical significance of their data, such as that provided by the MCID score.

6MWT, 6-minute walk test; Acu-TENS, acupuncture points; CAT, chronic obstructive pulmonary disease assessment test; COPD, chronic obstructive pulmonary disease; FEV1, one-second forced expiratory volume; GOLD, Global Initiative for Chronic Obstructive Lung Disease; MBS, modified Borg scale; MCID, minimal clinically important difference score; mMRC, modified British Medical Research Council questionnaire; MRCS, Medical Research Council scale; PR, pulmonary rehabilitation; RCT, randomised controlled trial; SGRQ, St. George respiratory questionnaire.

All authors contributed to the conception, design, and preparation of the manuscript, as well as read and approved the final manuscript.

None declared.

None declared.

All authors abide by the Association for Medical Ethics (AME) ethical rules of disclosure.