key: cord-0741794-7emiap4h
authors: Hu, Haiyin; Ji, Zhaochen; Qiang, Xiaoyu; Liu, Shigang; Sheng, Xiaodi; Chen, Zhe; Liu, Fanqi; Wang, Hui; Zhang, Junhua
title: Chinese Medical Injections for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Network Meta-analysis
date: 2021-12-17
journal: Int J Chron Obstruct Pulmon Dis
DOI: 10.2147/copd.s335579
sha: c97c80d0d21b4a9d3dc80b326c2fe5514e6db093
doc_id: 741794
cord_uid: 7emiap4h

BACKGROUND: The World Health Organization has indicated that chronic obstructive pulmonary disease (COPD) may become the third leading cause of death by 2030. Acute exacerbation of COPD (AECOPD) is an important process in clinical treatment. Recent studies have shown that Chinese medical injections (CMI) are effective against AECOPD, but the effective difference among different CMIs remains unclear. The aim of this network meta-analysis (NMA) is to compare the therapeutic effect of various CMIs. METHODS: We conducted an overall, systematic literature search in the China National Knowledge Infrastructure, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve randomized controlled trials (RCTs) of CMIs for AECOPD published up to January 2021. The Cochrane risk of bias tool was used to assess the risk of bias. Stata 13.1 and WinBUGS 14.3 were used for data analyses. RESULTS: In total, 103 RCTs involving 8767 participants and 23 CMIs were included. The results indicated that among all treatments conventional Western medical therapy (WM) plus Dengzhanxixin injection (DZXX) led to the best improvement in the clinical efficacy and the ratio of forced expiratory volume in one second (FEV(1)) to forced vital capacity (FVC) (FEV(1)/FVC), with surface under the cumulative ranking curve (SUCRA)=80.47% and 98.55%, respectively. Moreover, Shenmai injection (SM) plus WM and Reduning injection (RDN) plus WM led to the best improvement in the FEV(1) (SUCRA=80.18%) and the ratio of forced expiratory volume in one second to the predicted value (FEV(1)%, SUCRA=87.28%). Shengmai injection (SGM) plus WM led to the most considerable shortening in the length of hospital stay (SUCRA=94.70%). Cluster analysis revealed that WM+DZXX had the most favorable response for clinical efficacy and FEV(1), as well as clinical efficacy and FEV(1)/FVC, WM+RDN had the most favorable response for clinical efficacy and FEV(1)%, WM+SGM had the most favorable response for clinical efficacy and length of hospital stay. CONCLUSION: WM+DZXX, WM+RDN, and WM+SGM were noted to be the optimum treatment regimens for improving in clinical efficacy, FEV(1), FEV(1)/FVC, FEV(1)% and reducing the hospital stay length of AECOPD patients. Considering the limitations this NMA may have, the current results warrant further verification via additional high-quality studies.

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, persistent airflow restriction and abnormal airway inflammation. When the related respiratory symptoms worsen continually, warranting conventional medication changes, the condition is defined as acute exacerbation of COPD (AECOPD). [1] [2] [3] AECOPD can severely impact the patient's daily life and impair their lung function. 4 According to the World Health Organization, the COPD is expected to be the third leading cause of death by 2030 globally. [5] [6] [7] [8] In the Asia-Pacific region, COPD incidence is estimated to be as high as 6.2% and rising. 9 In 2019 an expert consensus on antiinfective therapy for AECOPD in China showed that COPD prevalence in Chinese residents aged >40 and >60 years was 13.7% and >27.0%. 10−12 Mortality risk increases significantly in patients with AECOPD. 13 Corticosteroids and long-acting bronchodilators are recommended as the first-line therapies for AECOPD along with the additional use of antibiotics if required. 14 However, long-term treatment with systemic corticosteroids is immunosuppressive, which increases the risk and severity of viral infections. 15 Moreover, the wide application of antibiotics has led to bacterial resistance . 16 These factors can reduce treatment efficacy further. 17 Chinese medical injections (CMIs) are widely used in clinical practices. 16 Some clinical trials have evaluated the efficacy of CMIs for patients with AECOPD and reported their effectiveness in inhibiting inflammation, regulating immune function, and alleviating symptoms. [18] [19] [20] Recent systematic reviews have also shown that CMIs are effective for treating AECOPD, [21] [22] [23] [24] [25] but the effective difference among different CMIs remains unclear. Therefore, in this study, we performed a network metaanalysis (NMA) of all published RCTs on CMIs for treating of AECOPD to compare the therapeutic effect of the different CMIs used.

The study protocol was registered on PROSPERO (Registration No. CRD42021236247; https://www.crd. 

We included RCTs with participants diagnosed with AECOPD (based on diagnosis and treatment guidance of chronic obstructive pulmonary disease). 26 The experimental group received a CMI plus conventional Western medical therapy (WM) (including oxygen inhalation, spasmolysis, anti-asthmatic and nutritional support, and antibiotic treatment), whereas the control group received WM alone or another CMI plus WM. No restrictions on language, sex, age, and disease course were imposed.

The main outcome was clinical efficacy and the evaluation criteria were as follows:

• Significantly effective: clinical symptoms and signs such as cough and dyspnea disappeared or improved significantly, the pulmonary rales disappeared or decreased, and laboratory examinations showed normal results at the end of the treatment. • Effective: clinical symptoms, signs, and laboratory examinations, all improved at the end of the treatment. • Invalid: the condition neither improved nor worsened by the end of the treatment.

Next, clinical efficacy rate was calculated as [(significantly effective cases+effective cases)/total cases]×100%. The secondary outcomes were as follows:

• Lung function: this included forced expiratory volume in one second (FEV 1 ), the ratio of FEV 1 to the predicted value (FEV 1 %), and the ratio of FEV 1 to forced vital capacity (FEV 1 /FVC), as recommended by the Global Strategy for Prevention, Diagnosis and Management of COPD. 14 • Length of hospital stay: this is closely related to the cost of hospitalization and the economic burden of patients. 27 The improvements in the lung function and length of hospital stay were expressed as means ± standard deviations.

We excluded studies including AECOPD patients with other comorbidities such as gastroesophageal reflux disease, depression, and osteoporosis-all of which are associated with COPD exacerbation and COPD development acceleration. 28 We also excluded studies where a combination of multiple TCM injections was used, or where TCM injections were combined with other therapies (decoction, acupuncture, moxibustion, etc). Finally, conference articles, duplicated literature, unavailable studies, and studies with missing data were all excluded. 

Two researchers independently conducted literature screening and data extraction. Eligible studies were reviewed and the following data were abstracted using a pre-established data extraction table: age, sex, sample size, intervention/ control measures, treatment course, outcomes, and adverse reactions. The selected studies and extracted data were crosschecked by two authors and if there were any disagreements they were resolved through consulting with a third party.

The quality of the included studies was evaluated using the Cochrane risk of bias tool recommended by the Cochrane Handbook for Systematic Reviews Version 5.3. Study quality was evaluated on the basis of seven aspects: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. 29 For each item the use of the right method was rated as low risk of bias, unclear description was rated as unknown risk of bias, and the use of an incorrect method was rated as high risk of bias. All results were cross-checked by two authors and if there were any disagreements they were resolved through consulting with a third party.

Dichotomous outcomes were measured as odds ratios (ORs), whereas continuous outcomes were measured as mean differences (MDs). When 95% confidence interval (CI) of the ORs and MDs did not contain 1 and 0, respectively, the differences were considered statistically significant. Stata 13.1 was used to draw a network plot-where thicker lines indicated a higher number of the RCTs and a larger dot indicated a larger sample size. An inconsistency test was specifically needed when a closed loop formed in network plot. An inconsistency test was used to mainly evaluate the degree of consistency between the direct comparison results and indirect comparison results. Here P≥0.05 indicated low inconsistency in the closed loop, whereas P<0.05 indicated significant inconsistency.

We used the Markov Chain Monte Carlo method with a random-effect model on WinBUGS 14.3 to perform Bayesian NMA. The iterations were set to 400,000. The first 100,000 times were used for annealing to eliminate the influence of the initial value and the last 300,000 times were used for sampling. The results are reported as the ORs and MDs with their respective 95%CIs. Surface under the cumulative ranking curve (SUCRA) was used to rank the efficacy of each intervention. The publication bias was assessed by comparison-adjusted funnel plot with Begg's test. Cluster analysis was conducted using STATA 13.1 to determine the dependency between outcomes and thus to the best interventions. This study was reported in accordance with PRISMA extension for network metaanalysis. 30

After our preliminary literature search 2430 studies were obtained of which 345 duplicates were removed. A total of 1653 articles were excluded after reading titles and abstracts because they were non-RCTs, non-AECOPD studies, concomitant use of other therapies, included 

patients with other diseases, animal studies, or systematic reviews. Furthermore, 329 studies were excluded after reading full texts because they reported unrelated outcomes, incomplete data, or lack of full text. Finally, 103

RCTs were included. PRISMA flow diagram for study selection is shown in Figure 1 .

The characteristics of included studies are shown in Table 1 . One hundred and three RCTs comprised a total of Supplementary Table S1 . The treatment duration ranged from 3 to 35 days.

The assessment of risk of bias for all the included studies is illustrated in Figure 2 and Supplementary Table S2 .

Regarding random sequence generation, 32 studies used the correct stochastic grouping method and thus were assessed to have low risk, whereas two studies grouped with registration order and thus were assessed to have high risk. The remaining 69 studies reported "random allocation" without specific methods and were assessed to have unclear risk.

Regarding allocation concealment, 102 studies were assessed to have unclear risk because they did not describe their allocation methods. Moreover, one study allotted drugs with a specially assigned person and was assessed to have low risk.

Regarding blinding of participants and personnel, only three studies concealed the used interventions from patients, and thus, these studies were assessed to have low risk. The other 100 studies were assessed to have unclear risk.

Regarding blinding of outcome assessment, 42 studies did not describe the blinding of outcome assessment, but all results assessed using objective indicators, thus, these studies were assessed to have low risk. However, 16 studies used subjective indicators alone to assess result and thus were assessed to have high risk. The remaining studies were deemed to have unclear risk.

Regarding incomplete outcome data, the outcome data of all the included studies were complete, and thus, these studies were assessed to have low risk.

Regarding selective reporting, one study was assessed to have high risk due to the inconformity between its methods and results. The other studies did not report selectively and were assessed to have low risk. All the included studies were deemed to have unclear risk of other bias because some details in these studies (eg, conflict of interest and registration scheme) were unclear.

In total, 99 studies evaluated clinical efficacy, included 22 CMIs and 8326 patients. There are 98 two-arm and one three-arm RCTs, included 23 direct and 230 indirect comparisons. The network plot is presented in Figure 3A .

One closed loop formed in the network plot, and it required an inconsistency test of the direct and indirect comparisons in this closed loop. The results indicated that the inconsistent probability between direct and indirect comparisons in the closed loop WM-(WM+TRQ)-(WM +XBJ) was low (ROR=2.261, 95%CI: 1.00,6.65, P=0.139, Supplementary Figure S1 and Figure S2 ).

The Table 2 .

WM+DZXX was ranked the best in clinical efficacy (SUCRA=80.47%), followed by WM+DH (SUCRA= 66.78%) and WM+HJT (SUCRA=65.66%). All SUCRA rankings for clinical efficacy are presented in Supplementary  Table S3 .

In total, 18 RCTs using eight of the CMIs reported FEV 1 improvements in AECOPD patients. The 18 RCTs (one three-arm and 17 two-arm) included 1715 patients. In total, 9 direct and 27 indirect comparisons formed. The network plot is presented in Figure 3B .

In the network plot of the included comparisons that reported FEV 1 Figure S3 and Figure S4 ).

Of the eight CMIs, only WM+TRQ revealed significant differences in FEV 1 compared with WM alone (MD=0.42, 95%CI: 0.22, 0.62, Table 3 ). The network 

analysis showed no significant differences between other comparisons. In the probability rankings, WM+SM (SUCRA=80.18%) was the most likely to improve FEV 1 in the patients with AECOPD, followed by WM+TRQ (SUCRA=66.73%), WM +SXN (SUCRA=58.81%). SUCRA rankings for FEV 1 are presented in Supplementary Table S3 .

In 27 two-arm RCTs, the changes in FEV 1 /FVC before and after treatment with 11 CMIs plus WM in 2362 patients with AECOPD were examined. This led to 11 direct and 55 indirect comparisons forming. The network plot for FEV 1 /FVC is shown in Figure 3C .

Of Table 4 . Other comparisons did not reach statistical significance. WM+DZXX was ranked the best in FEV 1 /FVC (SUCRA=98.55%), followed by WM+RDN (SUCRA=77.15%) and WM+KA (SUCRA=69.47%). SUCRA rankings for FEV 1 /FVC are presented in Supplementary Table S3. FEV 1 % FEV 1 % was reported in 20 two-arm RCTs, including nine CMIs and 1838 patients-forming 9 direct and 36 indirect comparisons. The network plot for FEV 1 % is shown in Figure 3D . WM+RDN Table 5 .

For FEV 1 %, WM+RDN (SUCRA=87.28%) was ranked the best, followed by WM+XYP (SUCRA=69.75%), WM +XBJ (SUCRA=64.86%). SUCRA rankings for FEV 1 % are presented in Supplementary Table S3 .

Eight two-arm RCTs including five CMIs and 717 patients recorded the length of hospital stay and formed 5 direct and 10 indirect comparisons. The network plot for length of hospital stay is shown in Figure 3E .

WM+SGM (MD = −6.9, 95%CI: −10.89, −2.9) and WM+TRQ (MD = −3.07, 95%CI: −4.97, −1.15) led to a shorter length of hospital stay than did WM alone ( Table 6 ). There was no significant difference in other comparisons.

In terms of shortening the length of hospital stay, WM+SGM (SUCRA=94.70%) was ranked the best, followed by WM+SM (SUCRA=57.49%) and WM+XYP (SUCRA=55.85%). SUCRA rankings for length of hospital stay are presented in Supplementary Table S3 .

Cluster analysis was performed on clinical efficacy and FEV 1 , clinical efficacy and FEV 1 /FVC, clinical efficacy and FEV 1 %, clinical efficacy and length of hospital stay so as to find the best interventions. The results showed that the most favorable response by WM+DZXX were for clinical efficacy and FEV 1 as well as for clinical efficacy and FEV 1 /FVC, by WM+RDN were for clinical efficacy and FEV 1 %, and by WM+SGM were for clinical efficacy and length of hospital stay (Figure 4 ).

Begg's test was used to identify the possible publication bias related to the different interventions and the impact of small sample studies. The results demonstrated potential publication bias in the funnel plot of clinical efficacy (P=0.000), suggesting that the publication bias was small in the funnel plot for FEV 1 (P=0.347), FEV 1 /FVC (P=0.359), and FEV 1 % (P=0.381, Supplementary Figure S5 ). Because the number of included studies that reported the length of hospital stay was <10, we did not assess the publication bias for length of hospital stay. 3378 palpitation (n=1), headache (n=1), diarrhea (n=1), and dizziness+chest distress+xerostomia (n=2). Of the 12 TCM injections, the highest incidence of adverse reactions was noted after WM+SXT (16.67%), followed by WM +CKZ (11.36%) and WM+RDN (10.45%). Adverse reactions were shown in Figure 5 and Supplementary Table S4 . WM alone and TCM injections plus WM both had the following common adverse reactions: fever, nausea and vomiting, xerostomia, gastrointestinal reaction, and rash ( Figure 6 ). In patients with AECOPD, WM+DZXX had the highest likelihood of being the best treatment for improving both the clinical efficacy and FEV 1 /FVC, WM+SM, WM +RDN and WM+SGM had the highest likelihood of being the best treatment for improving FEV 1 , FEV 1 %, and length of hospital stay, respectively.

The cluster analysis revealed that WM+DZXX had the most favorable response for clinical efficacy and FEV 1 , as well as clinical efficacy and FEV 1 /FVC, WM+RDN had the most favorable response for clinical efficacy and FEV 1 %, WM+SGM had the most favorable response for clinical efficacy and length of hospital stay.

DZXX is a sterile aqueous solution composed of Erigerontis Herba extract, has been used in China for many years. Its main active components include flavonoids and phenolic acids. 31 Flavonoids can activate blood and dissolve stasis as well as inhibit the inflammatory reaction in the lung and the synthesis of collagen fiber to prevent pulmonary fibrosis. 32 Clinical studies have shown that compared with WM alone, DZXX achieved better efficacy when administered to patients with moderately severe COPD, it could not only reduce inflammation, but also improve hemorheological indicators and lung function. 33 Experimental studies show that DZXX can decrease transforming growth factor β1 activity to inhibit fibroblast proliferation, collagen fiber and extracellular matrix synthesis, delaying or improving the process of airway remodeling and irreversible obstruction in COPD. [34] [35] [36] RDN is composed of Artemisiae Annuae Herba, Lonicerae Japonicae Flos, and Gardeniae Fructus, is generally administered as an intravenous injection to treat cold, cough, upper respiratory infections, and acute bronchitis, and it has a good curative effect in clinics. 37, 38 Previous studies have shown that cryptochlorogenic acid, neochlorogenic acid, and geniposide-the main active substances of RDN 39-44 -can increase superoxide dismutase (SOD) activity, suppress myeloperoxidase (MPO) activity, and reduce the wet/dry (W/D) ratio and total leukocyte and neutrophil numbers, 38 it can thus be antiinflammatory, improve immunity, and alleviate damage caused by the diseases. 45, 46 In addition, a network analysis identified two key compounds (CFA and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) for RDN-all of which play critical roles in the treatment of inflammatory diseases. 47 The normal respiratory movement of the human body involves the joint participation of nerve cells that produces the respiratory rhythm and those that regulate the respiratory movement in the central nervous system. 48 Studies have shown that the irreversible airflow limitation of COPD may be related to the abnormal excitability of the respiratory center. 48 SGM is composed of Red Ginseng, Ophiopogonis Radix, and Schisandrae Chinensis Fructus. Here, Ophiopogonis Radix nourishes the yin (nutrition and fluid in the human body, which nourishes various organs 49 ), Schisandrae Chinensis Fructus astringents the qi (vital energy, regarded as a driving force of biological activities in the human body, including both nutrient substances and organ functions 50 ) and has antitussive effects, and Red Ginseng tonifies qi and enhances immunity. 51 The combination of these herbs affects the respiratory center and then relieves dyspnea in COPD patients. 52, 53 Modern studies have also indicated that SGM can improve pulmonary ventilation function, thus increasing the alveolar diffuse area, adjusting the airflow ratio, reducing myocardial oxygen consumption and glucose metabolism, and enhancing gland and endocrine function, as a result, the whole body function is adjusted, qi becomes tonified and blood is activated. 54 A meta-analysis reported that SGM+WM has significant efficacy in COPD treatment, where it improves clinical efficacy and lung function, regulates immune function, and shortens disappearance time of lung rales. 55, 56 Adverse reactions appeared in both treatment group and control group of included studies. However, the specific correlation between the TCM injections used and adverse reactions could not be determined. The incidence of adverse reactions was high in WM+SXT (16.67%), WM+CKZ (11.36%), and WM+RDN (10.45%), compared with WM alone. Thus, the safety of CMIs still needs further evaluation.

The number of original studies on this research topic met the basic requirements for this NMA, but the quality of these studies were not high. In particular, the limitations of our study were as follows:

(1) Only 31.07% of the studies used the correct random method, which may have resulted in selective biases.

(2) Most of the studies did not mention the blinding of participants or personnel and allocation concealment, which may have resulted in implementation biases.

(3) Of all the included studies, 15.53% merely used subjective indicators as the outcome evaluation index, which may have resulted in measurement bias.

(4) The 103 included studies did not mention protocol registration and conflict of interests, therefore, the sources of other bias could not be determined.

(5) The funnel plot for clinical efficacy indicated the possibility of publication bias. The missing contents from ongoing studies and gray literature may result in publication bias. 55 (6) None of the included studies restricted the TCM syndromes of AECOPD patients. However, patients with different TCM syndromes who were treated with the same intervention may not represent the real effect of the TCM drugs.

(7) The participant age and treatment duration varied in the included studies, which may have affected the stability of results. (8) All included studies were conducted in China, this might weaken the generalization of the results.

In conclusion, WM+DZXX had the highest likelihood of being the best treatment for improving both the clinical efficacy and FEV 1 /FVC, WM+SM, WM+RDN and WM +SGM had the highest likelihood of being the best treatment for improving FEV 1 , FEV 1 % and length of hospital stay, respectively. Combined with cluster analysis results, DZXX, RDN or SGM plus WM were noted to be the optimum treatment regimens for improving the condition of patients with AECOPD. However, the quality of studies evaluating the efficacy of various CMIs is not good. Therefore, additional high-quality studies are warranted.

COPD, chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; TCM, traditional Chinese medicine; CMI, Chinese medical injection; RCT, randomized controlled trial; CKZ, Chuankezhi injection; DH, Danhong injection; DS, Danshen injection; DZXX, Dengzhanxixin injection; HH, Honghua injection; HJT, Hongjingtian injection; HQ, Huangqi injection; KA, Kangai injection; KDZ, Kudiezi injection; QKL, Qingkailing injection; RDN, Reduning injection; SF, Shenfu injection; SGM, Shengmai injection; SM, Shenmai injection; SHL, Shuanghuanglian injection; SXN, Shuxuening injection; SXT, Shuxuetong injection; TRQ, Tanreqing injection; XYP, Xiyanping injection; XBJ, Xuebijing injection; XST, Xuesaitong injection; ZCL, Zhichuanling injection; Salvianolate, Salvianolate injection; WM, conventional Western medical therapy; ADR, adverse reaction; FEV 1 , forced expiratory volume in one second; FEV 1 /FVC, ratio of forced expiratory volume in one second to forced vital capacity; FEV 1 %, ratio of forced expiratory volume in one second to the predicted value.

The raw data supporting the conclusion of this article will be made available by the corresponding author (Hui Wang) without undue reservation.

This study is an overview of the literature thus ethics approval was not needed.

The study group consented to publish.

Thanks to the authors of the included studies to provide primary data. 

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Anti-inflammatory and Immunization Properties of Re-Du-Ning Injection in Treatment of AECOPD with Phlegm-heat Stagnated in the Lung Syndrome

Effect of Tanreqing on pulmonary function of acute exacerbation of COPD (Syndrome of retention of phlegm and heat in Fei)

Clinical research of Xuebijing parenteral solution on the coagulation status and lung function of patients with acute exacerbation of chronic obstructive pulmonary disease

Therapeutic Effect of Sofren Injection in Treatment of Acute Exacerbations of COPD

Clinical observation of Shenfu Injection in the treatment of acute exacerbation chronic obstructive pulmonary disease

Tanreqing injection in the treatment of 50 cases of acute chronic obstructive pulmonary disease

Evaluation on the efficacy of Tanreqing on 42 patients with chronic obstructive pulmonary disease of acute exacerbation

Observation of curative effect of Danhong injection on acute exacerbation of chronic obstructive pulmonary disease

Clinical experience of Chuankezhi injection in the treatment of chronic obstructive pulmonary disease

Observation on curative effect of Tanreqing injection on acute attack of chronic obstructive pulmonary disease

Observation on the Therapeutic Effect of Removing Heat-phlegm Method in the Sequential Treatment of Chronic Obstructive Pulmonary Disease in Acute Exacerbation Period

Clinical observation on the treatment of acute exacerbation of chronic obstructive pulmonary disease by integrated traditional Chinese and western medicine

Therapeutic effect of Shenmai injection on 38 cases of chronic obstructive pulmonary disease during acute episode

Clinical Study of Reduning Treatment of Acute Exacerbation Phase of Chronic Obstructive Pulmonary Disease

Clinical observation of Tanreqing injection in treating 72 cases of acute exacerbation of chronic obstructive pulmonary disease

Observation of therapeutic effect of Danzhanxixin injection on acute exacerbation of chronic obstructive pulmonary disease

Therapeutic effect of Tanreqing injection on 50 cases of acute exacerbation of COPD

Clinical observation on Tanreqing adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease

Effects of Shuxuenlng Injection on the Levels of Serum Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Acute Exacerbated Chronic Obstructive Pulmonary Disease Patients

Effects of Tanreqing injection on acute exacerbations of chronic obstructive pulmonary disease

Clinical observation on 39 cases of acute exacerbation of chronic obstructive pulmonary disease treated with integrated traditional Chinese and western medicine

Application of Xuebijing injection in acute exacerbation of chronic obstructive pulmonary disease

Clinical observation of Shengmai injection in acute exacerbations of chronic obstructive pulmonary disease(COPD)

Effect of Tanreqing Injection on Cytokines and Lung Function in Patients with acute exacerbation of Chronic Obstructive Pulmonary Disease

Clinical analysis of Reduning injection in the treatment of acute exacerbation of chronic obstructive pulmonary disease

Effect of Xuebijing in the treatment of acute exacerbation of chronic obstructive pulmonary disease and its mechanism

Clinical study on salvianolate injection in treatment of acute exacerbation of chronic obstructive pulmonary disease

Clinical observation of 100 cases of acute exacerbation of chronic obstructive pulmonary disease treated with integrated traditional Chinese and western medicine

Effects of Chuankezhi injection with airway humidification on mechanical ventilation function of patients with acute exacerbation of chronic obstructive pulmonary disease

40 cases of acute exacerbation of COPD treated by Kudiezi injection combined with western medicine

Clinical observations on treating respiratory system emergency by Chuankezhi Injection

Observation on curative effect of Tanreqing injection on patients with acute exacerbation of chronic obstructive pulmonary

Effects of Acupoint Injection of Astragali Radix Injection on Immune and Respiratory Function of Patients with Sequential Mechanical Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Clinical observation of Tanreqing injection in the treatment of acute exacerbation of chronic obstructive pulmonary

Influence of astragalus injection on serum cytokines and lung function in acute exacerbation of chronic obstructive pulmonary disease

Clinical observation of atomized inhalation of Tanreqing injection in treating acute exacerbation of chronic obstructive pulmonary disease

Application of Danhong injection in emergency treatment of patients with Acuet Exacerbation Chronic Obstructive Pulmonary Disease

Clinical observation of Danhong injection in the treatment of 42 cases of acute exacerbation of chronic obstructive pulmonary disease in the elderly. Health Vocational Educ

Effect analysis of Tanreqing injection in adjuvant treatment of 120 elderly patients with AECOPD

Tanreqing Injection in Adjuvant Treatment of 26 Cases of Acute COPD

Effect of Xuebijing injection on plasma D-dimer and fibrinogen in patients with AECOPD

Application Significance Reduning Injection in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Tanreqing injection in treating 32 cases of acute exacerbation of chronic obstructive pulmonary

Clinical study on the adjuvant treatment of chronic obstructive pulmonary disease with Shenmai injection

Observation of curative effect of astragalus injection on acute exacerbation of chronic obstructive pulmonary disease

Efficacy of integrated traditional Chinese and western medicine in treating acute exacerbation of chronic obstructive pulmonary disease in the elderly

Clinical Observation on Atomized Zhichuanling Injection for the Treatment of 60 Cases with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Clinical Analysis of Qingkailing Combined Medication Treatment of Elderly Patients with COPD Infection

Randomized controlled study in parallel with acute exacerbation chronic obstructive pulmonary disease of Danhong injection combined with western medicine

Qingkailing aerosol inhalation treated 36 cases of acute exacerbation of chronic obstructive pulmonary disease

Efficacy analysis of Honghua injection combined with routine treatment for 47 cases of chronic obstructive pulmonary disease in aggravation stage

Influence of Xiyanping injections therapy on inflammation factors and lung function of old patients with acute exacerbation chronic obstructive pulmonary disease

Randomized Controlled Trial of Tanreqing Injection in Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease(Syndrome of Retention of Phlegm-Heat in the Lung)

Curative effect of Kudiezi injection on acute phase of chronic obstructive pulmonary disease

Clinical Observation of Shuanghuanglian Injection in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Effects of Shenfu injection on the patients with acute exacerbation of chronic obstruction pulmonary disease

Therapeutic effect of Xuesaitong injection on acute exacerbation of chronic obstructive pulmonary disease

Clinical effect of Reduning injection on acute exacerbation of chronic obstructive pulmonary disease

Clinical observation of tanreqing injection in treatment of acute exacerbation of COPD

Danhong injection in the treatment of acute exacerbation of chronic obstructive pulmonary disease and its effect on hemorheology

Tianjin Higher Education Institution through Tianjin Municipal Education Commission (No. TD13-5047).

The authors report no conflicts of interest in this work.

The International Journal of COPD is an international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus is given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is indexed on PubMed Central, MedLine and CAS. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors.Submit your manuscript here: https://www.dovepress.com/international-journal-of-chronic-obstructive-pulmonary-disease-journal

International Journal of Chronic Obstructive Pulmonary Disease 2021: 16