Effect of Liuzijue breathing exercise on patients with stable chronic obstructive pulmonary disease:a systematic review and meta-analysis

Abstract

Backgrounds:Chronic obstructive pulmonary disease(COPD) is a common,preventable disease of airflow limitation that accounts for the third leading deaths of any disease process in the worldwide. Health benefits of Liuzijue breathing exercise on patients with stable COPD has assessed. This study was designed to perform a systemic review and meta-analysis of the effect of Liuzijue breathing exercise on patients with stable COPD.

Methods: Published articles from inception to 2020 were conducted using electronic searches. Two independents reviewers performed data extraction.The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies.

Results:A total of 16 eligible trials with 1039 patients with stable COPD were identified. Compared with control group,the pool meta-analysis of Liuzijue breathing exercise showed a significant improve in FEV1 [MD=-0.16,95%CI (0.09,0.23), P<0.00001], FEV1% [MD=9.71, 95%CI(8.44,10.98), P<0.00001], FEV1/FVC(%) [MD=4.81,95%CI(2.12,7.51),P=0.0005],6MWD [MD=21.89,95%CI（14.67, 29.11）,P<0.00001] , health-related quality of life [SMD=-0.84,95%CI（-1.12,-0.55，P<0.00001] and mMRC [MD= -0.73,95%CI (-0.96,-0.50), P<0.00001]. The observed effect was more pronounced for interventions that were short term and medium-term duration of study. Liuzijue interventions also showed improvement in the secondary outcome measures.

Conclusions:In this systematic review and meta-analysis ,Liuzijue breathing exercise can improve lung function,exercise endurance and health-related quality of life of patients with stable COPD.

1. Background

Chronic obstructive pulmonary disease (COPD) is a respiratory system disease that is characterized by persistent respiratory tract symptoms and fixed airflow limitation^[1]. Its main clinical symptoms are dyspnea, chronic cough with mucous production,chest tightness and wheezing^[2–3].Currently, about 400 million people suffers from COPD which it is the third leading cause of death in the worldwide^[4].Additionally, the medical burden of COPD is significant ranking fifth in the world’s economic burden of disease^[5]. According to statistics, the U.S. government spent nearly $50 billion on treatment of COPD in 2010^[6].In China, about 1.5 million people die from COPD in China every year^[7] .COPD presents a significant challenge to the health care provider worldwide^[8–9].

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends that patients with acute exacerbation of COPD should be given drug therapy, while patients in stable stage should actively cooperate with non-drug therapy base on drug therapy^[9]. Non-drug treatments mainly include oxygen therapy and pulmonary rehabilitation training. Pulmonary rehabilitation training is widely used for COPD, and its purpose is to relieve symptoms, improve quality of life, reduce medical burden^[10].its efficacy is widely recognized^{[1, 9, 11]}.

As one of the traditional fitness exercises with Chinese national cultural characteristics, Liuzijue is a cheap, simple and effective lung rehabilitation training method, which plays a positive role in regulating respiratory system, exercise endurance and quality of life on patients with stable COPD according some clinical studies^[12–14].Despite the potential benefits of Liuzijue breathing exercise for COPD management,various design and methodologic weaknesses have consistently been identified across studies.In addition, there lacks a systematic review and meta-analysis of clinical therapeutic effect about Liuzijue breathing exercise on patients with COPD. So this study is a systematic review and meta-analysis of published literature on the application of Liuzijue breathing exercise in patients with stable COPD, in order to provide high-quality evidence synthesis and decision basis for the rehabilitation of COPD patients.

2. Methods

 2.2 Inclusion And Exclusion Criteria

2.2.1 Inclusion criteria

(i) Only RCTs regarding the efficacy of Liuzijue exercise for COPD were included.(ii)Patients were diagnosed with COPD in a stable phase according to the Global Initiative for Chronic obstructive pulmonary disease (GOLD), and no acute exacerbation occurred in all patients within six months before entering the trial.(iii)The baseline interventions included routine basic treatment of western medicine ,oxygen therapy,usual care,conventional respiratory therapy,health education and were equally implemented in both groups.(iv)The experimental group participated in Liuzijue breathing exercise, while the control group received health education ,or conventional breathing exercise or or no intervention.

2.2.2 Exclusion criteria

(i)The trial design with not scientific and rigorous was excluded; (ii)The full text which could not obtained through various channels was excluded;(iii)Qualitative studies, animal experiments, case reports and conference abstract reviews were excluded ;(iv)Documents with incomplete data or data problems were excluded ; (v)Documents with inconsistent main outcome indicators were excluded; (vi)Patients with COPD accompanied by other complications were excluded;(vi)Patients with COPD are in an unstable phase were excluded.

2.3.Data extraction and synthesis

Data were extracted independently by two reviewers(PG and FT) according to inclusion and exclusion criteria, and then cross-checked.If there is a dispute, it will be settled through discussion.The extracted contents included:(i) The basic materials of the literature, such as the author, the year of publication,journal, etc.;(ii) Specific details of experimental design, such as randomization, allocation and concealment, blinding of participants and personnel, basic data, intervention program, outcome, duration of intervention and follow-up time of the study subjects.If the study data is found incomplete, contact the author by phone or email to obtain the data. If the relevant data is not obtained in the end, the research will be excluded.When RCT with multiple studies was involved, the experimental group and control group related to this study were extracted, as shown in Fig. 1.

2.4.Types of outcome measures

The primary outcome included [forced expiratory volume in one second(FEV1)], [as a percentage of predicted expiratory volume in one second,FEV1(%)] ,The ratio of forced expiratory volume to forced vital capacity in the first second[FEV1/FVC༈%༉], exercise endurance(6 minutes walking distance,6MWD]. And the secondary outcome comprised Health-related quality of life( St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment test(CAT),Dyspnea index( Modified Medical Research Council Dyspnea Scale,mMRC).

2.5 Literature quality evaluation

Jadad score was used to evaluate the methodological quality of each RCTs included ^[15], with a total score of 7 points. Scores < 4 were considered as low quality studies, while scores ≥ 4 were considered as high quality studies ^[16].The risk of bias was assessed using the evaluation criteria recommended by the Cochrane Handbook 5.1.0 ^[17], "low risk bias", "high risk bias" and "unclear" (lack of relevant information or uncertainty of bias) were assessed for each of the included literatures.The quality evaluation of literatures were conducted independently by two reviewers(PG and YM).Any controversy occurring during the evaluation process were discussed with a third reviewer(WL)and resolved by consensus.

2.6 Statistical analysis

The RevMan5.3 and Stata14.0 software were used for meta analysis.As an priori analysis,we also analyzed the property of data across three intervention durations,defined as short-term(≤3months), medium-term (6 months), and long-term(12months). Heterogeneity test: judged by chi-2 test and I² test, if P < 0.05,I² ≤ 50% indicate that there is homogeneity among the studies, and fixed effect model was used for analysis.If P ≤ 0.05༌I² > 50%, indicating statistically heterogeneity, random effect model was used for analysis.Finally, we used the funnel plots and Egger’s regression asymmetry test to detect publication bias .To prove the reliability of our meta-analysis

results,a sensitivity analysis were conducted by removing each study one by one to evaluate the consistency and quality of results.If variables in the studies included in this meta-analysis were continuous, we used the mean difference (MD) and 95% confidence interval (CI) to analyze the studies,otherwise,standardized mean difference (SMD) was used when variables were inconsistent. We considered P values less than 0.05 to be statistically significant.

3. Result

3.2 Study Characteristics

A total 16 studies^[18–33] involving 1039 individuals were selected for this meta-analysis, one studies^[23] were published in English, and fifteen studies^{[18–22,24−33]} were published in Chinese,six of which were dissertations^{[24,28–29,31−33]}. All eligible studies were published from 2008 to 2019. There were 13 studies with a sample size ≥ 40 participants,and the average age of participants is > 60 years old. The quality of each study was assessed using the Jadad scale, Five studies were high-quality ^{[22–23, 29, 31, 33]},Ten studies were low-quality^{[18–21,24−28,30,32]}.The basic characteristics of the included studies were shown in Table 1

 3.3 Methodological Quality Assessment

The methodological quality of all included studies were evaluated according to the bias risk assessment tools provided by the Cochrane Handbook. All of the included trials described randomized allocation,and they were low risk in the fields of randomized allocation.Twelve studies were classified as having an unclear risk in the fields of allocation concealment^{[18–21,24−28,30−32]} and one was high risk^[22].There was high risk of bias in the domain of blinding of participants and personnel,only three studies^{[23, 29, 33]}used single-blind method,but no specific method of blinding was mentioned in these studies.Only five of them were shown to blind their outcome assessment^{[21,23–24,32−33]}.All trials reported methods with a low risk of incomplete outcome data .With regard to selective outcome reporting bias, ten studies were determined as low risk and the remaining were determined as unclear risk.All studies were graded as unclear risk of other bias.These results were summarized in Fig. 2.

3.4 Effects Of Liuzijue Breathing Exercise On Primary Outcomes

3.4.1 Effects of Liuzijue breathing exercise on pulmonary function

Pulmonary function test was the main objective index to judge airflow limitation. FEV1,FEV1% and FEV1/FVC(%) are important component of pulmonary function.Seven trials^{[19,21,23,26−29]}used FEV1 to evaluate the therapeutic effect of Liuzijue on stable COPD patients.The fixed effects model was utilized to integrate the results(I² = 7%).The results showed that,overall,Liuzijue breathing exercise significantly improved the FEV1 compared with the control group [MD=-0.16,95%CI (0.09,0.23), P < 0.00001,Fig. 3], the efficacy on FEV1 were noticeable in both short term duration of study[MD = 0.14, 95%CI (0.06, 0.23), P = 0.001;Fig. 3] and medium-term duration of study [MD = 0.19, 95%CI (0.07, 0.30), P = 0.002;Fig. 3].Eleven studies^{[21,23–24,26−33]}used FEV1% to assess the improvement of pulmonary function of COPD patients by Liuzijue breathing exercise.The fixed effects model was conducted to incorporate the results,they had high heterogeneity (I² = 63%).The effect size of the studies^{[21,23–24,26−33]}showed that Liuzijue exercise could significantly improve the FEV1%[MD = 9.71,95%CI(8.44,10.98), P < 0.00001;Fig. 4]. The treatment effect on FEV1% were also prominent in both short term [MD = 11.02, 95%CI(9.39,12.66),P < 0.00001;Fig. 4] and medium-term duration of study [MD = 7.71,95%CI (5.69,9.73), P < 0.0001;Fig. 4].Nine trials used FEV1/FVC(%) to evaluate the enhancement of lung function of COPD patients.The fixed effects model was conducted to incorporate the results (I² = 50%).The effect size of the studies^{[19,23,26–29,31−33]}showed that Liuzijue breathing exercise could significantly improve the FEV1/FVC(%)[MD = 4.81, 95%CI (2.12, 7.51),P = 0.0005;Fig. 5].The effect of FEV1/FVC(%) had significant amelioration for COPD in short term [MD = 5.35, 95%CI (1.93,8.78),P = 0.002;Fig. 5] and with marginal in medium-term duration of study [MD = 2.99, 95%CI (-1.11,7.09), P = 0.15;Fig. 5]

3.4.2 Effects of Liuzijue breathing training on exercise endurance

Nine studies used 6MWD to evaluate the effect of Liuzijue on exercise endurance of COPD patients.The random effects model was adopted to incorporate the results(I² = 43%).The overall effect of the studies^{[18–25, 33]}found that Liuzijue breathing exercise was associated with significantly increase the length of 6MWD compared with the control group [MD = 21.89,95%CI(14.67, 29.11),P < 0.00001,Fig. 6],The effect on 6MWD were remarkable in both short term duration of study[MD = 16.78, 95%CI (14.18,19.38),P < 0.0001,Fig. 6] and medium-term duration of study [MD = 42.72, 95%CI (28.36, 57.08),P < 0.00001,Fig. 6],but there was no significant effect in the studies with a long-term duration of study [MD = 23.11, 95%CI (-3.35,49.57), P = 0.09;Fig. 6].

3.5 Effects of Liuzijue exercise on secondary outcomes

3.5.1 Effects of Liuzijue exercise on health-related quality of life

Five of 7 trials used CAT to evaluate the effect of Liuzijue exercise on health-related quality of life of COPD patients while the other 2 articles used SGRQ .There was high heterogeneity among the included studies(I² = 65%), and a random effect model was used for merge the results.The overall effect of the studies^{[20–24,29−31,33]}showed significantly improvement the health-related quality of life compared with the control group [SMD==-0.84,95%CI(-1.12,-0.55),P < 0.00001,Fig. 7], The effect on health-related quality were outstanding in short term duration of study[SMD=-0.70, 95%CI(-1.01,-0.38),P < 0.001,Fig. 7],medium-term duration of study [SMD=-1.10,95%CI (-1.67, -0.52),P = 0.0002,Fig. 7],and long-term duration of study [SMD=-0.57,95%CI(-0.91,-0.23), P = 0.001; Fig. 7].

3.5.2 Effects of Liuzijue exercise on dyspnea

Only three studies^{[20, 22, 33]}used the mMRC to evaluate dyspnea of patients with COPD .The random effects analysis was managed to merge the results (I² = 42%).The results showed that Liuzijue breathing exercise significantly lowered the mMRC compared with the control group [MD= -0.73,95%CI (-0.96,-0.50), P < 0.00001,Fig. 8]

3.6.Adverse events

None of the articles informed adverse events. Thence,this information could not be searched from the RCTs analyzed.

3.7.Sensitivity analysis

Some results of this study had high heterogeneity eg.FEV1(%) ,FEV1/FVC(%) and health-related quality, by removing single studies i.e. the study^[26] of FEV1(%) ,the study^[32]of FEV1/FVC(%) ,study^[31] of health-related quality,the sensitivity analyses showed obvious changes in the statistical significance of outcomes.

3.8.Publication bias

As shown from the Egger’s asymmetry tests,there was little indication of publication bias on the these outcomes(p = 0.764 for FEV1;p = 0.436 for FEV1%;p = 0.076 for 6MWD;p = 0.348 for health-related quality,respectively),only the outcome of FEV1/FVC%(p = 0.048)was showed publication bias.

4. Discussion

To the best of our knowledge,this is the first systematic review with meta-analytical method to objectively evaluate the therapeutic effects of Liuzijue breathing exercise for stable COPD patients.All eligible RCTs were published between 2008 and 2019,indicating that it is a newly broadening research hotspot. The purpose of this current review was to evaluate the efficacy and safety of Liuzijue exercise for COPD patients.No adverse events occurred in all studies, and the positive findings in the current review are in line with previous meta-analyses of randomized controlled trials investigating the beneficial effects of other Chinese traditional exercises (eg.Tai Chi, Baduanjin and Meditative movement) for COPD patients^[34–36].

In our study,we created subgroups based on the different intervention duration time of Liuzijue breathing exercise to evaluate the overall effect and each subgroup’s effect,which would informed COPD patients of the effect of different intervention duration times. Generally, compared with conventional therapy,our study found that Liuzijue breathing exercise was helpful for COPD rehabilitation as assessed by FEVI,FEV1(%), FEV1/FVC (%) ,6MWD,mMRC and health-related quality.

6MWD has been used as a simple and valid evaluation parameter for exercise tolerance of COPD patients^[37–39]. In our study,we found the distance of the 6MWD in the Liuzijue group was increased compared with the distance in the control group.In subgroup analysis, whether it was a short-term intervention or a medium-term intervention ,Liuzijue breathing exercise had a positive effect for improving 6MWD of COPD patients.However, there was no significant effect in long-term duration of study,it may be lack of study of long-term intervention of LiuziJue breathing exercise on COPD patients.Declining of exercise endurance and lung function are the main characteristics of COPD, and there are numerous reasons for the decreasing of patients' exercise ability. It is generally believed that the patient’s movement is restricted to airflow obstruction, lung hyperinflation and gas exchange barriers during the activity process^[40–41], furthermore, the movement restriction makes the patient unable to engage in related sports which causes the patient's exercise ability to further decline ^[42], then this will form a vicious circle. Liuzijue contains breathing exercises and limb movement, which it is not only beneficial to the flexibility and functional coordination of the upper limb muscles, but it also strengthens the function of the lower limbs.Thus Liuzijue breathing exercise could prolong the 6MWD of COPD patients.

FEV1, FEV1%, FEV1/FVC (%) are important indicators to reflect the degree of airway ventilation and obstruction of COPD patients,which can assess the severity of the patient’s clinical symptoms and disease severity ^[43]. In our study, Liuzijue breathing exercises improved patients' lung function [i.e.,FEV1, FEV1(%), FEV1/FVC (%) ]compared with control group by the pool effect of our meta-analysis.In subgroup analysis,Liuzijue exercise had a good effect on the three index of lung function [FEV1, FEV1(%) ] in COPD patients regarding short-term or mid-term duration intervention.This finding may be because Liuzijue can enhance the strength of respiratory muscle^[44],Also “Xu, Si and He” word tactic of Liuzijue exercise can extend expiratory time, improve the airway pressure,avoid premature closure of the airway, increase pulmonary ventilation function in patients with COPD^[45].However,our finding is contrary to Tong HX ^[46]'s research viewpoint that the LiuziJue of traditional health qigong cannot improve the lung function of COPD patients. For this reason, we carefully read Tong’s study of meta-analysis and found that there is only one article about Liuzijue's intervention in COPD patients included in his study of meta-analysis, which is not sufficient to demonstrate the effectiveness of Liuzijue's intervention in COPD patients.In the actually practice of Liuzijue exercise, the breathing method is beneficial to improve the abdominal muscle tension, increase movement range of the diaphragm up and down, enhance the strength of respiratory muscle, and thus obtain the greatest improvement of lung function.So patients with COPD could choice Liuzijue breathing exercise for improving respiratory function.

Currently,improving COPD patients' dyspnea and enhancing their exercise endurance were the main target through Liuzijue exercise. Declining of exercise endurance and respiratory function directly affects the quality of life of COPD patients.Therefore, the assessment of the health-related quality of life of patients should be an important part of the effect of treating patients. CAT respiratory questionnaire and the SGRQ respiratory questionnaire were widely used for assessing the quality of life of patients with COPD.In our study,the overall effect size showed that Liuzijue breathing exercise significantly improved the health-related quality of life compared with the control group.Additional,good evidence was founded in our study that Liuzijue exercise decreased mMRC score of dyspnea. The underlying mechanism is that Liuzijue breathing exercise has a positive effect on the T cell immune function of patients with stable COPD and prevent patients from getting sick more easily^[31],otherwise,as a form of traditional fitness exercise ,limb training of Liuzijue can effectively relieve dyspnea symptoms during activities while adjusting the respiratory function and relaxing the whole body function, so it has better effects on health-related quality of life of COPD patients^[47–48].

In subgroup analysis of our study, Liuzijue exercise also had good evidence of the effect on FEV1,FEV1(%), FEV1/FVC (%),6MWD and health-related quality of life in both short term and medium-term duration of study.However,the long-term intervention duration of Liuzijue breathing exercise had no effect may be because there is too little literature to prove the evidence. From our study,we suggested that the intervention duration of Liuzijue lasts at least 3 to 6 months.

4.1 Limitation

Athough,we has comprehensive analysis and assess all eligible studies,it still has some limitation.First,15 of sixteen RCTs in this meta-analysis were published in Chinese and little of relevant foreign RCTs,there may be publication bias that the result of this study were regional.Secondly,In our study,some results had high heterogeneity with regards to intervention intensity, duration,and frequency that may have contributed to unwanted heterogeneity and may have further influenced the outcomes. Even though our classification of intervention durations (i.e., short, medium and long term), the relatively small number of studies included in each category did not allow us to effectively explanation the heterogeneity underlying the different studies in our random effect models. Thirdly, most of the studies showed only the randomized trials, but no specific methods of random sequence generation, RCTs of allocation concealment, and blinding of outcome assessment.There were only three studies which reported single blinding. The methodological quality of many of the included RCTs was generally low and might have a high risk of bias.

4.2 Practical implications

5. Conclusion

In summary, this meta-analysis of RCTs suggested that Liuzijue breathing exercise had positive effects in field of lung function, exercise endurance,health-related quality of life and dyspnea of patients with stable COPD.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors agree to publish this article

Availability of data and materials

The data analysed and materials used in this study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare that there are no conflicts of interest.

Funding

This research was supported by the National Society Science Foundation of China (Grant No.BLA150064), the Educational Research Project of Hunan Province (Grant No.19C1330), and the Higher Education Teaching Reform Project of Hunan Province (Grant No.2019-1165)

Authors’ Contributions

PG and FT contributed equally to this work. PG and FT comprehensively searched the medical database and collected and extracted consistent randomized clinical trials; PG and FT, and YM discussed and analyzed data together;PG wrote papers;and FT provided suggestions for writing preparation ;WL conceived the idea for this paper and revised the paper. The final version of the article is determined after review by all authors.

Acknowledgements 

This thesis would not have been possible without the consistent and valuable reference materials that I received from my supervisor(WL) and my colleague(FT), whose insightfulguidance and enthusiastic encouragement in the course of my shaping this thesis definitely gain my deepest gratitude. 

References

1.Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.Eur Respir J. 2017;49(3):1700214. 

2.Kessler R, Partridge MR, Miravitlles M, et al. Symptom variability in patients with severe COPD:a pan-European cross-sectional study.EurRespirJ.2011;37(2):264–72.

3.Medical Research Council Committee on the Aetiology of Chronic bronchitis.Definition and classification of chronic bronchitis for clinical and epidemiological purposes. A report to the Medical Research Council by their Committee on the aetiology of chronic bronchitis. Lancet 1965;1(7389):775–9.

4.Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, Nair H,Gasevic D, Sridhar D, Campbell H, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5(2):020415

5.World Health Organization. Programmes and projects: Chronic Respiratory Diseases: Burden of COPD Web page. Geneva, Switzerland: World Health Organization; 2020. Available from: https://www.who.int/respiratory/copd/burden/en/

6.Adeloye D, Chua S, Lee C, et al, Global Health Epidemiology Reference Group.Global and regional estimates of COPD prevalence: systematic review and meta-analysis.J Glob Health 2015;5:020415.

7.Zhang XE, Zhang CL. Research progress on the epidemiology and economic burden of chronic obstructive pulmonary disease.China Chronic Disease Prevention and Control, 2017,25(6): 472 -476

8.Duffy SP, Criner GJ. Chronic Obstructive Pulmonary Disease: Evaluation and Management. Med Clin North Am. 2019 May;103(3):453-461

9.Singh D, Agusti A, Anzueto A, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019;53(5):1900164.

10.Ries AL,Bauldoff GS,Carlin BW,et al.Pulmonary rehabilitation:joint ACCP/AACVPR evidence-based clinical practice guidelines[J].Chest,2007, 131(5_suppl):4S-42S.

11.Vijayan VK. Chronic obstructive pulmonary disease. Indian J Med Res. 2013;137(2):251-269.

12.Li P, Liu J, Lu Y, Liu X, Wang Z, Wu W. Effects of long-term home-based Liuzijue exercise combined with clinical guidance in elderly patients with chronic obstructive pulmonary disease. Clin Interv Aging. 2018;13:1391-1399. .

13.Ng BH, Tsang HW, Jones AY, et al. Functional and Psychosocial Effects of Health Qigong in Patients with COPD: A Randomized Controlled Trial.The Journal of Alternative and Complementary Medicine, 2011, 17(3):243—251.

14.Wu W, Liu X, Liu J, Li P, Wang Z. Effectiveness of water-based Liuzijue exercise on respiratory muscle strength and peripheral skeletal muscle function in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:1713-1726.

15.Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Control Clin Trials, 1996, 17:1-12.

16.Kjaergard LL, Villumsen J, Gluud C. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med, 2001, 135: 982-989.

17.Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011].The Cochrane Collaboration, 2011. Available from www. cochrane-handbook.org

18.Fang DP, Liu Y, Zhu XL,et al. The application and effect of "Liu Zi Jue Breathing Exercise" in the continuous nursing of patients with chronic obstructive pulmonary disease in stable stage. Journal of Nursing Management, 2012,12(11):813-815.(Chinese)

19.Chen JX,Deng LJ. The rehabilitation effect of traditional "six-character breathing exercise" on patients with stable COPD.Chinese Journal of Rehabilitation Medicine,2009,24(10):944-945. (Chinese)

20.Zhang MM,Zhang Q,Shu QQ,et al. Efficacy evaluation of Liuzijue breathing exercises assisted long-term home oxygen therapy in patients with chronic obstructive pulmonary disease.Chinese Journal of Practical Nursing,2019(27):2108- 2113.(Chinese)

21.Sun N,Li DP,Sun Y.The effect of Liuzijue combined with lip-reduction abdominal breathing training on lung function and quality of life in patients with stable COPD.Medical Clinical Research,2019,36(5):1003-1004 .(Chinese)

22.Deng LJ,Zhang WX,Chen JX.Comparative study on the effect of Liuzijue and whole body breathing exercises on the respiratory function of elderly patients with chronic obstructive pulmonary disease.Journal of Rehabilitation,2018,28(03):57-61.(Chinese)

23.Wu W, Liu X, Li P, Li N, Wang Z. Effect of Liuzijue Exercise Combined with Elastic Band Resistance Exercise on Patients with COPD: A Randomized Controlled Trial. Evid Based Complement Alternat Med. 2018:2361962.

24.Jiang MN. The effect of strengthening LiuziJue on the stable respiratory function of patients with chronic obstructive pulmonary disease with deficiency of lung and spleen Qi. Hunan University of Traditional Chinese Medicine, 2017.(Chinese)

25.Zhang WX,Chen JX,Zheng GH,et al.The effect of "Liu Zi Jue" breathing method on exercise endurance of patients with chronic obstructive pulmonary disease in stable stage.Nursing Research,2009,23(32):2957 -2958.(Chinese)

26.Zhu Z.Effects of Health Qigong on Respiratory Function of 61 Cases of COPD in Stable Phase.Journal of Nanjing University of Traditional Chinese Medicine, 2011, 27 (03):235-237. (Chinese)

27.Chen JX,Zhang WX,Zheng GH,et al.Application of "Liu Zi Jue" breathing method in pulmonary rehabilitation of patients with stable COPD.Journal of Fujian College of Traditional Chinese Medicine,2008,18(06):3-4.(Chinese)

28.Li DX. Research on the effect of "Liu Zi Jue" on chronic obstructive pulmonary disease from the perspective of respiratory mechanics . Fujian University of Traditional Chinese Medicine, 2011.(Chinese)

29.Chen FX. The effect of Liuzijue on serum inflammatory factors in patients with stable chronic obstructive pulmonary disease. Fujian University of Traditional Chinese Medicine, 2019.(Chinese)

30.Lan Y , Han X, Wang YY, et al. The effect of tiotropium bromide combined with "Liu Zi Jue" exercise on the quality of life and lung function of patients with chronic obstructive pulmonary disease in stable stage. World Traditional Chinese and Western Medicine Combined Magazine, 2016, 11(10): 1369-1371+1395.(Chinese)

31.He JF. The effect of "Liu Zi Jue" breathing method in the treatment of stable COPD and its influence on T lymphocyte subsets . Beijing University of Traditional Chinese Medicine, 2019. (Chinese)

32.Li R. The Intervention Study of Health Qigong·Liu Zi Jue on the Stable Chronic Obstructive Pneumonia in the Elderly. Beijing Sport University, 2018.(Chinese)

33.Wang LB. The effect of Liuzijue combined resistance training on BODE index and quality of life in patients with stable chronic obstructive pulmonary disease. Shanghai University of Sport, 2015.(Chinese)

34.Ding, M.; Zhang,W.; Li, K.; Chen, X. Effectiveness of T’ai Chi and Qigong on Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis. J. Altern. Complement. Med. 2014, 20, 79–86.

35.Liu SJ, Ren Z, Wang L, Wei GX, Zou L. Mind Body (Baduanjin) Exercise Prescription for Chronic Obstructive Pulmonary Disease: A Systematic Review with Meta-Analysis. Int J Environ Res Public Health. 2018;15(9):1830.

36.Wu LL, Lin ZK, Weng HD, Qi QF, Lu J, Liu KX. Effectiveness of meditative movement on COPD: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2018; 13: 1239-1250.

37.Butland RJ, Pang J, Gross ER, Woodcock AA, Geddes DM. Two-, six-,and 12-minute walking tests in respiratory disease. Br Med J (Clin Res Ed). 1982;284(6329):1607–1608.

38.Poulain M, Durand F, Palomba B, et al. 6-minute walk testing is more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with COPD. Chest. 2003;123(5):1401–1407.

39.Chen H, Liang BM, Tang YJ, et al. Relationship between 6-minute walk test and pulmonary function test in stable chronic obstructive pulmonary disease with different severities. Chin Med J (Engl). 2012;125(17):3053–3058.

40.Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2016;138:16–27.

41.Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med 2015;373:1241–9.

42.Spruit MA, Polkey MI, Celli B, et al. Predicting outcomes from 6- minute walk distance in chronic obstructive Pulmonary disease[J]. J Am Med Dir Assoc, 2012, 13(3):291-297.

43.Liu X, Li P, Xiao L, Lu Y, Li N, Wang Z, Duan H, Li J, Wu W. Effects of home-based prescribed pulmonary exercise by patients with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial. Trials. 2019 Jan 11;20(1):41

44.Jia H . The effect of respiratory muscle exercise on the respiratory function of patients with COPD during the remission period of dyspnea [J]. Modern Chinese Doctor, 2008, 46 (20): 144.

45.Guan FG, Wang T, Huang YL, etc. The effect of "Si" on the lung function and life satisfaction of patients with stable chronic obstructive pulmonary disease. Journal of Rehabilitation, 2016, 26(3): 50-53.

46.Tong H, Liu Y, Zhu Y, Zhang B, Hu J. The therapeutic effects of qigong in patients with chronic obstructive pulmonary disease in the stable stage: a meta-analysis. BMC Complement Altern Med. 2019 Sep 4;19(1):239.

47.Huang Y. The effect of Liuzijue breathing exercises on abdominal surgery patients with COPD. Hunan University of Traditional Chinese Medicine, 2016.

48.Liu A, Pan XY, Zeng WK, et al. The effect of "Liu Zi Jue" breathing training method on the constitution and quality of life of elderly patients with lung cancer after lung cancer surgery. Journal of Hunan University of Traditional Chinese Medicine,2018,38(03): 352-355.