Study Protocol Systematic Review Medicine ®

OPEN

Efficacy and safety of acupoint autohemotherapy

in treating stable chronic obstructive pulmonary
disease
Protocol for a systematic review and meta-analysis
Haidu Hong, MSa, Chushuan Huang, MSb, Chumin Chen, MSa, Rui Zhou, MSc, Jieying Li, MSa,
∗
Jianbo Liu, PhDb, , Xiaohong Liu, PhDb

Abstract
Background: Chronic Obstructive Pulmonary Disease (COPD) is a clinically common chronic disease with the characteristic of
recurrent attacks, difficulty of cure and high morbidity, disability, death rates. COPD exerts a great burden on patients, families and
society. Acupoint Autohemotherapy (AA) is a traditional Chinese medicine (TCM) treatment by taking the patient’s own venous blood and
injecting them at acupoints, combined with the continuous stimulation of blood and the specific efficacy of the acupoint itself. It has been
proved to be useful in pulmonary treatment and rehabilitation of COPD patients. However, the efficacy of AA on COPD patients has not
been fully statistically evaluated. In this study, we aim to systematically examine the efficacy and safety of AA for COPD patients.
Methods: Data from all English and Chinese databases, including Medline, Cochrane Library, Embase, China National Knowledge
Infrastructure Database, Wanfang Database, China Biomedical Literature Database and Chongqing VIP information, will be used to
conduct a systematic and comprehensive literature search. The range of date is from inception to July 2019. Randomized controlled
trials (RCTs) related to AA and western medicine in the treatment of COPD will be included. Quality of included trials will be assessed
according to the risk of bias tool of Cochrane Handbook 5.1.0. The GRADE approach will be used to rate the certainty of the evidence
of estimates derived from meta-analysis. RevMan 5.3 will be used for data synthesis, sensitivity analysis, meta-regression analysis,
subgroup analysis and risk of bias assessment. A funnel plot will be developed to evaluate reporting bias, and Begg and Egger tests
will be used to assess funnel plot symmetries. Grading of recommendations assessment, development and evaluation system will be
utilized to assess the quality of evidence.
Results: This systematic review and meta-analysis aims to summarize the direct and indirect outcomes for AA and western
medicine on COPD patients and evaluate its efficacy and safety. The results will be submitted to a peer-reviewed journal once
completed.
Conclusion: The systematic review will provide evidence to assess the efficacy and safety of AA and western medicine in the
treatment of COPD patients.
PROSPERO registration number: PROSPERO CRD42019137189
Abbreviations: 6MWD = 6-minutes walking distance, AA = acupoint autohemotherapy, AE = the incidence of acute
exacerbations, BMI = body mass index, CAT = COPD assessment test, COPD = chronic obstructive pulmonary disease, CRQ =
chronic respiratory questionnaire, FEV1 = forced expired volume in one second per predicted, FEV1% = the percentage of forced
expiratory volume in one second, FEV1/FVC% = forced expired volume in one second to forced vital capacity, mMRC = modified
British medical research council, PRISMA = preferred reporting items for systematic reviews and meta analyses, PRISMA-P =
preferred reporting items for systematic review and meta-analysis protocols, RCT = randomized controlled trial, SGRQ = George’s
respiratory questionnaire, TCM = traditional Chinese medicine.
Keywords: acupoint autohemotherapy, chronic obstructive pulmonary disease, meta-analysis, protocol, systematic review

This work is supported by the Science and technology program of Guangzhou, China (201803010053), the Traditional Chinese Medicine Administration of Guangdong
Province, China(20174007), the Inheritance Workshop of Guangdong Province famous TCM doctor Xiaohong Liu, China(201805).
The authors have no conflicts of interest to disclose.
a
The First Clinical College, Guangzhou University of Chinese Medicine, b The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, c Clinical
Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, China.
∗
Correspondence: Jianbo Liu, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China (e-mail: [email protected]).
Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
How to cite this article: Hong H, Huang C, Chen C, Zhou R, Li J, Liu J, Liu X. Efficacy and safety of acupoint autohemotherapy in treating stable chronic obstructive
pulmonary disease. Medicine 2019;98:38(e17291).
Received: 29 August 2019 / Accepted: 30 August 2019
http://dx.doi.org/10.1097/MD.0000000000017291

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Hong et al. Medicine (2019) 98:38 Medicine

1. Introduction performed, research that may be included in this review needs to

Chronic Obstructive Pulmonary Disease (COPD) is a disease first meet the following criteria:
characterized by persistent respiratory symptoms and restricted 1. Randomized controlled trial;
airflow,[1] and is a clinically common chronic disease with the 2. COPD patients without restrictions in sex, age, and race, and
characteristic of recurrent attacks, difficulty of cure and high the ratio of forced expiratory volume in one second (FEV1) to
morbidity, disability, death rates. It exerts a great burden on forced vital capacity (FVC) was less than 70% or FEV1 was
patients, families and society. According to reports, COPD is less than 80% of predicted values according to the 2019
currently the fourth leading cause of death in the world.[2] With Global Initiative for Chronic Obstructive Lung Disease
the decline in environmental quality, it is expected to rise to the (GOLD) criteria;
third place by 2020,[3] becoming a health problem that cannot be 3. AA intervention lasted no less than 4 weeks;
ignored. However, the overall pathogenesis of COPD is not 4. Outcome measures included FEV1, FEV1%, FEV1/FVC%,
entirely clear, and the current treatments are mainly to relieve AE, 6MWD, SGRQ, CRQ, mMRC, CAT, or BMI.
symptoms, which have significant limitations. Traditional
Chinese medicine (TCM) has the advantages of multiple targets The following study designs or publication types will be
and systematic regulation, and its importance in the treatment of excluded:
COPD has been highlighted.[4] 1. Patient diagnosed with COPD but has other diseases such as
Autohemotherapy originates from Soviet in the 1940s and respiratory failure, bronchiectasis, bronchial asthma, lung
1950s to treat tuberculosis hemoptysis by intramuscular cancer, etc.
injection, then it spread to China. Rui Jin, chief professor of 2. Other interventions such as moxibustion, acupressure,
Guangzhou University of TCM, created the Meridian Blood Chinese medicine, etc. were combined in the treatment.
Injection Therapy which is also called Acupoint Autohemother- 3. Duplicate or non-clinical research literature.
apy (AA) later, a TCM characteristic therapy that combine the 4. Containing other confusing signs or the data cannot be
continuous stimulation of blood with the action of acupoints to extracted, or lacking of outcome measures.
treat diseases by injecting the patient’s venous blood into
acupoints.[5,6] It is a combination of TCM meridian theory, These trails can be adopted if multiple intervention data are
available. If data for comparing multiple interventions is not
acupuncture, multi-component stimulation of blood cells and
regulation of immune function of the body. Initially, the method directly available, we will attempt to obtain the raw data by
was used to treat patients with malaise, malnutrition and anemia sending an email to corresponding author of the article. If the
data is not available at the end, these documents will also be
after malaria. After repeated clinical exploration, research and
development, AA was used for more diseases treatments excluded.
especially for respiratory diseases including COPD,[7] asthma,[8] 2.2.2. Population. RCTs with a clear diagnosis of stable COPD
cough variant asthma[9] and has achieved satisfactory results. were considered in accordance with the GOLD diagnostic
At present, there are many clinical trials showing the efficacy criteria.[10] The stable phase of COPD usually means that there is
and safety of AA combined with western medicine in the no acute exacerbation within 4 weeks. Patients were included
treatment of COPD. But the sample size varies, and it lacks regardless of nationality, gender, age, and ethnicity.
certain persuasive power. The aim of this study is to
comprehensively collect randomized controlled trials (RCTs) 2.2.3. Interventions. The control group was treated with
for the treatment of COPD with AA and western medicine, and to western medicine. The main treatment option was using inhaled
provide evidence for clinical practice by evaluating the efficacy corticosteroids combined with bronchodilators, such as Salmet-
and safety through the Cochrane systematic evaluation. erol Xinafoateand Fluticasone Propionate Powder for inhalation
and Budesonide and formoterol Fumarate Powder for Inhalation.
At the same time, according to the patient’s condition, using
2. Methods conventional therapy including bronchodilators, expectorants
and other drugs combined with oxygen therapy, nutritional
2.1. Study registering and reporting
support therapy. The experimental group was treated with AA on
The study protocol has been registered on PROSPERO (Interna- the basis of the control group.
tional Prospective Register of Systematic Reviews)
(CRD42019137189). This protocol is developed in accordance 2.2.4. Outcome measures. Primary outcome indicator: total
with the Preferred Reporting Items for Systematic Reviews and effective rate of clinical treatment.
Meta-analyses Protocols (PRISMA-P). Any protocol modifications Secondary outcome indicator:
made during the performing of the review will be recorded in the 1. Pulmonary function:FEV1, FEV1%, FEV1/FVC%;
publication of the final report. The PRISMA Extension Statement 2. The incidence of Acute Exacerbations (AE);
is used to ensure all aspects of methods and findings are reported. 3. Exercise endurance: 6-minutes walking distance(6MWD);
4. Health-related quality: St. George’s respiratory questionnaire
2.2. Eligibility criteria (SGRQ)and Chronic respiratory questionnaire(CRQ);
5. Health status: modified British medical research council (mMRC),
The PICOS (Population-Intervention-Comparators-Outcomes- COPD assessment test (CAT)and body mass index (BMI).
Study design) framework was adopted as the eligibility criteria
for the review as follows. 2.3. Data sources and search strategy
2.2.1. Study design. Whether or not blinding, allocation The work of document retrieval will be carried out from
concealment, reporting withdrawal and loss of follow-up were 3 English databases (Medline, Cochrane Library, Embase) and

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4 Chinese databases (China National Knowledge Infrastructure publication bias will also be considered. Four levels of quality
Database, Wanfang Database, SinoMed, and Chongqing VIP of evidence will be used: high, moderate, low, or very low.
information)from inception to July 2019. We will also
undertake a targeted gray literature search on Clinical Trials.
2.6. Dealing with missing data
gov and the International Clinical Trials Registry Platform
Search Portal to identify clinical trials, which are in progress or If necessary, we will contact both senior and/or corresponding
completed. And the following sources will also be searched author of articles through email or telephone for further
including of Google Scholar, Web of Science and Baidu Scholar information about any missing data or unclear measurement
to identify trial protocols and other information. Furthermore, scales. If no one responds or sufficient information cannot be
more studies will be identified after examining the reference lists obtained in this way, we will analyze the available data. The
of all retrieved articles. potential impact of insufficient data on the review results will be
These following combined texts and Medical Subject Headings took into account in the discussion section.
(MeSH) terms are used by us to search in the sources: ’autologous
blood’, ’autohemotherapy’, ’self-blood’, ’acupoint’, ’injection’, 2.7. Statistical analysis
’chronic obstructive pulmonary disease’, ’COPD’, ’pulmonary
disease’. The search terms will be ’autologous blood’ OR The statistical analysis will be performed according to their
’autohemotherapy’ OR ’self-blood’ AND ’acupoint’ OR ’injec- commendations of the cochrane handbook and using the
tion’ AND ’chronic obstructive pulmonary disease’ OR ’COPD’ software of cochrane collaboration, RevMan 5. 3, available
OR ’pulmonary disease’. from the cochrane website. All outcomes will be continuous
variables. The standardized mean difference and its 95% CIs will
be calculated. Initially, a fixed-effect model will be used to
2.4. Study selection and data extraction compare with the outcomes expressed in the same scale. The
Two researchers (Chushuan Huang, Rui Zhou) extracted data heterogeneity of the effects of trials will be evaluated by the Q2
independently from the literature downloaded from 7 databases test and the I2 test. Heterogeneity will be considered as substantial
and managed by EndNote X9. Two researchers (Chumin Chen, if the I2 statistic≥50% and P < .10. If heterogeneity is considered
Rui Zhou) independently screened the included studies, extracted as substantial, reasons for this heterogeneity will be searched for
data, evaluated the quality of included studies and cross-checked and a random-effect model could be used for comparison.
with each other according to the established selection criteria. If Sensitivity analysis, meta-regression, and subgroup analysis
there are disagreements about the articles between the 2 might be conducted if there are potential sources of heterogeneity.
researchers, objections will be delivered to the third researcher Qualitative synthesis will be performed if data extraction is
(Haidu Hong) and final decision will be made by him. First, the insufficient.
preliminary screening will be performed by reading the title and
abstract of the obtained literature. Studies that fail to meet the 2.8. Patient and public involvement
eligibility criteria will be excluded. Then, full text of the articles
will be retrieved to further determine whether they are included. This part is not covered in this study.
The screening process will be presented with reference to the
PRISMA statement as Figure 1. Microsoft Excel will be used to 3. Ethics and dissemination
extract data and collect relevant information. A self-made data
extraction form will be used to extract data, including the first We aim to publish this systematic review in a peer-reviewed
author’s name, year of publication, study design, intervention, journal. This study aims at providing available evidence for the
and control group information, sample size, duration of efficacy and safety of AA on the treatment of stable COPD
intervention, and outcomes, including FEV1, FEV1%, FEV1/ patients. Ethical approval will not be demanded since there is no
FVC%, AE, 6MWD, SGRQ, CRQ, mMRC, CAT, and BMI participant privacy involved.
results. We contacted the corresponding authors for additional
information if necessary.
4. Discussion
The latest research shows that the overall prevalence of COPD in
2.5. Quality assessment
China is 8.6%, while the subgroup of patients over 40-year-old
The Risk of Bias Tool (ROB) in Cochrane Handbook (5.1.0) will has nearly 99 million people, accounting for 13.7%.[11] If the
be used to assess the methodological quality of included trials by COPD is not controlled, it will develop into the final outcome of
two independent reviewers (Chumin Chen, Rui Zhou). Disagree- chronic pulmonary heart disease. At present, the main treatment
ments will be resolved by discussing with a third reviewer methods of Western medicine included smoking cessation,
(Xiaohong Liu). The ROB contains the following seven items: oxygen inhalation, lung volume reduction surgery, and drug
random sequence generation, allocation concealment, blinding of treatment (inhalation, oral administration, and systemic admin-
participants and personnel, blinding of outcome assessment, istration). However, there are still controversies and limitations
incomplete outcome data, selective reporting and other sources of in the development of individualized programs, the use of
bias. The judgment of each item is divided into three levels: low bronchodilators in the initial treatment, the side effects and
risk of bias, high risk of bias and unclear risk of bias. withdrawal of ICS and so on.[12]
We will evaluate the quality of evidence of the included studies COPD belongs to the category of ’lung distention’ in TCM
through the Grading of Recommendations Assessment, Devel- theory, which is due to repeated episodes of chronic lung diseases,
opment and Evaluation (GRADE) system. The limitations of the prolonged unhealed, resulting in lung, spleen, kidney 3 visceral
study, inconsistencies, indirect evidence, inaccuracies and damage, lung qi stagnation, chest fullness.[13] The theory of AA

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Hong et al. Medicine (2019) 98:38 Medicine

PRISMA 2009 Flow Diagram

Idenficaon

Records idenfied through Addional records idenfied

database searching through other sources
(n = 215 ) (n = 0)

Records aer duplicates removed

(n =139 )
Screening

Records excluded(n = 28 ) ˖
Records screened
NO related to acupoint
(n =47 )
autohemotherapy

Full-text arcles assessed Full-text arcles excluded,

for eligibility
Eligibility

with reasons (n = 8 )˖
(n = 19 ) NO Specified diagnosc
criteriaˈinappropriate
comparisons and unavailable
data
Studies included in
qualitave synthesis
(n = 11 )
Included

Studies included in
quantave synthesis
(meta-analysis)
(n = 11 )

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-
Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097

For more informaon, visit www.prisma-statement.org.

Figure 1. Flow diagram of study selection process.

comes from the TCM mainly. First, blood can nourish the weak globulin, enhance microcirculation. At the same time, it
state of the body, and the meridians can connect with the major antagonizes histamine, acetylcholine and serotonin to reduce
organs of the body and be effective through specific acupoints. the permeability of capillaries and inhibit allergic reactions.[15,16]
Second, the lungs lead the blood vessels and veins, so treatment Therefore, based on the theoretical basis of Chinese and Western
with blood can be effectively applied in lung diseases. Third, the medicine, AA is particularly suitable for improving the long-term
stimulation produced by acupuncture and blood synergy is long- weakness of COPD. In terms of treatment, the back-three-needles
lasting, slow, continuous and effective.[14] Modern research (BL13, BL11, BL12), EX-B1 and other pulmonary meridian
shows that the human body’s own blood is rich in hormones, acupoints are mainly used.[17] According to the different
antibodies, complement and other elements, does not have symptoms of the patients, other auxiliary acupoints such as
rejection and can stimulate the body to release more immuno- BL20 and ST36 are appropriately included.[18]

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GOLD2018: Global Strategy for the Diagnosis, Management and
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