Evidence Evaluation And Multi-center Randomized Controlled Clinical Study Of Reinforcing Earth To Generate Metal In The Treatment Of Chronic Obstructive Pulmonary Disease

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Evidence evaluation of ancient literature in the treatment of COPD with reinforcing earth to generate metal ObjectiveThis study systematically sorted out the ancient traditional Chinese medicine(TCM)literature related to chronic obstructive pulmonary disease(COPD),summarized the development of ancient treatment of COPD,then explored and evaluated the ancient literature evidence of the treatment of COPD with reinforcing earth to generate metal.MethodsThrough the questionnaire of TCM disease names of COPD,we identified the TCM disease names related to COPD as the key words,and then searched the ancient book citations which may be related to COPD in the Chinese medical classics(CD-ROM).We also established the rules for scoring the correlation of COPD citations,screened and analyzed the citations retrieved,further summarized the development of COPD in ancient times,and extracted the ancient evidence of COPD with reinforcing earth to generate metal.Results1.A total of 9770 ancient book citations were searched by TCM disease names,and 3069 citations related to COPD were finally included.The citations are from 174 different ancient books from 206 to 1934 AD.A total of 185 citations of COPD were screened out.The medical history and clinical symptoms described in these citations were similar to COPD.2.A total of 1173 TCM formulas for COPD were detected in ancient citations that may be COPD.The top five formulas were Shizao decoction,Xiaoqinglong decoction,Xiaobanxia decoction,Lingguizhugan decoction and Wuling powder.Patients with dyspnea as the main symptom,Gancao Fuzi decoction and Xiaoqinglong decoction were often used;Shizao decoction and Xiaoqinglong decoction were often used for patients with cough or chronic cough;Linggui Zhugan decoction and Mahuang powder were often used for for patients with phlegm.The composition of commonly used formulas mainly includes ginseng,pinellia ternata and ephedra.The representative formulas related to the treatment of COPD with the method of reinforcing earth to generate metal were Renshen Qiandonghua powder,Yigong powder and Sijunzi Decoction.3.A total of 78 TCM formulas for COPD were detected in the highly similar citations of COPD,the most commonly used formula was Renshen Kuandonghua ointment,which reflects the ancient doctors' thought of treating COPD with reinforcing earth to generate metal.The results of frequency analysis showed that the top 10 TCM formulas related to the treatment of COPD with the method of reinforcing earth to generate metal also included Yigong powder and Liujunzi Decoction.It can be seen that the treatment of COPD with the method of reinforcing earth to generate metal was not rare in ancient times.4.A total of 561 kinds of Chinese herbs for COPD were detected in ancient citations that may be COPD.After excluding the Chinese herb which plays an auxiliary role in the treatment of COPD,the top 10 herbs in frequency analysis were poria cocos,ginseng,pinellia ternata,cinnamon,almond,schisandra chinensis,pericarpium citri reticulatae,atractylodes macrocephalae,mulberry peel and ephedra.Among them,the herbs related to the method of reinforcing earth to generate metal included Poria cocos,ginseng,pinellia ternata,tangerine peel and atractylodes macrocephala.It is suggested that the herbs of invigorating the spleen and benefiting the lung was often used in the treatment of COPD.5.A total of 173 kinds of Chinese herbs for COPD were detected in the highly similar citations of COPD,after excluding the Chinese herb which plays an auxiliary role in the treatment of COPD,the top seven herbs in frequency analysis were almond,ginseng,farfara,tangerine peel,mulberry peel,pinellia ternata,schisandra chinensis,poppy,fritillaria and mume.Among them,the herbs related to the method of reinforcing earth to generate metal included ginseng,tangerine peel,pinellia ternata.It also suggests that the herbs of invigorating the spleen and benefiting the lung is more commonly used in the treatment of COPD.6.We analyzed the Zangfu pathogenesis of COPD,and screened out 30 citations related to the location of Zangfu.The results showed that there are multiple modes of transmission related to Zang and Fu of COPD,including lung-spleen,lung-kidney,lung-spleen-kidney transmission modes.Among them,the transmission mode of lung-spleen was the most common,and the correlation between lung and spleen was strong,suggesting that the treatment of COPD should be based on the treatment of the spleen,or focus on the lung and spleen to strengthen the spleen and benefiting the lung.ConclusionTraditional Chinese medicine has a long history in the treatment of COPD,which has rich theoretical basis and clinical application value.The method of reinforcing earth to generate metal in the treatment of COPD should be based on tonifying spleen-earth.The purpose of treating lung can be achieved by regulating and tonifying the acquired constitution,strengthening the spleen and benefiting the lung.In ancient times,there was evidence for the treatment of COPD with reinforcing earth to generate metal,and it played an important role.Part ? Meta-analysis and GRADE evidence evaluation of randomized controlled trials of reinforcing earth to generate metal therapy in the treatment of COPDObjective Meta-analysis was used to evaluate the efficacy and safety of reinforcing earth to generate metal method in the treatment of stable COPD,and the Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to evaluate the quality classification of clinical evidence.Methods We searched the domestic and foreign electronic databases,including Chinese Bio Medical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Chonqing VIP(CQVIP),Wanfang,Pub Med and Excerpta Medica Database(EMBASE).The search time range was from the beginning of database collection to August 2020.Randomized controlled trials(RCTs)of reinforcing earth to generate metal herbs versus placebo in the treatment of stable COPD were included.Referring to the bias risk assessment tool of Cochrane Collaboration Network,the methodological quality of RCT was evaluated.Revman 5.3 software was used for meta-analysis on the outcome indicators such as acute exacerbation of COPD,quality of life,exercise endurance and lung function.The quality of research evidence in meta-analysis was summarized and evaluated according to GRADE system.Results 1.Thirteen RCTs were included,involving 1933 patients.Most of the studies were carried out in China,and one study was completed by Australia and China.Six studies were published in SCI journals,and seven were published in core journals in China.The publication time range was 2010 to 2020.The treatment period of the study was 2-12 months,and the lung function of COPD patients was classified as Grade I to IV.2.Methodological quality assessment: 10 studies reported the generation of random sequences and the method of allocation concealment.All included studies were blinded to researchers and participants,and seven studies were blinded to outcome evaluators.Twelve studies reported data that were complete or baseline characteristics were balanced,and only one reported a drop-out rate of more than 20%.Six studies were registered or published in the database.3.Evaluation of acute exacerbation events: Meta-analysis showed that the therapy of reinforcing earth to generate metal significantly reduced the frequency of acute exacerbation of COPD(SMD =-0.82 times,95% CI:-1.43,-0.20,I2 = 95%),shortened the duration of acute exacerbation of COPD(MD =-3.13,95% CI:-4.15,-2.11,I2 = 2%).The curative effect of Chinese medicine group was better than placebo control group,the difference was statistically significant.However,there was no significant difference in reducing the incidence of acute exacerbation of COPD and shortening the time of first acute exacerbation.4.Evaluation of SGRQ score: compared with placebo,the therapy of reinforcing earth to generate metal failed to significantly reduce the SGRQ score of COPD,and the difference between them was not statistically significant(MD=-4.26 points,95% CI:-9.71,1.19;I2 =89%).However,subgroup analysis showed that the SGRQ score of COPD patients was significantly reduced by reinforcing earth to generate metal of Chinese herbal compound,and the curative effect of Chinese medicine group was better than that of placebo group(MD =-8.07 points,95% CI:-12.77,-3.37,I2 =67%),while the therapy of reinforcing earth to generate metal of single Chinese herb was not better than that of placebo group.5.Evaluation of COPD Assessment Test(CAT)score: compared with placebo,the therapy of reinforcing earth to generate metal failed to reduce the cat score,and the difference between them was not statistically significant(MD =-1.00 points,95% CI:-2.77,0.78;I2 =74%).However,subgroup analysis showed that the CAT score of COPD patients was significantly reduced by reinforcing earth to generate metal of Chinese herbal compound,and the curative effect of Chinese medicine group was better than that of the placebo group(MD =-2.64 points,95% CI:-4.04,-1.24;I2 = 0%),while the therapy of reinforcing earth to generate metal of single Chinese herb was not better than that of placebo group.6.Evaluation of other outcome indicators: the results of meta-analysis showed that in terms of improving exercise endurance,lung function,modified Medical Research Council(m MRC),Body Mass Index(BMI)and BODE index,the therapy of the reinforcing earth to generate metal was not better than placebo,and the difference between the two groups was not statistically significant.7.Evaluation of safety: 10 studies reported safety,a total of 357 cases of adverse events were reported,including 168 cases in the group of reinforcing earth to generate metal and 189 cases in the placebo group.There was no significant difference between the two groups(OR = 0.68,95% CI: 0.31,1.49;I2 =65%).There was no causal relationship between adverse events and interventions.The safety of herbals of reinforcing earth to generate metal was equivalent to that of placebo.8.Evaluation of GRADE: compared with placebo,the overall quality of evidence of reinforcing earth to generate metal was low to high,in which the therapy of reinforcing earth to generate metal could reduce the frequency of acute exacerbation of COPD(the quality of evidence was moderate)and shorten the duration of acute exacerbation(the quality of evidence was high),while the low to moderate quality of research evidence suggested that the therapy of reinforcing earth to generate metal was not better than placebo in reducing the incidence of acute exacerbation,prolonging the first time of acute exacerbation,and improving exercise endurance and lung function.The moderate quality evidence suggested that reinforcing earth to generate metal of Chinese herbal compound was better than placebo in significantly reducing the SGRQ and CAT scores of COPD patients.Conclusion The moderate to high quality evidence showed that the therapy of reinforcing earth to generate metal method can significantly reduce the frequency of acute exacerbation of COPD and shorten the duration of acute exacerbation.The moderate quality evidence indicated that reinforcing earth to generate metal of Chinese herbal compound can improve the quality of life and clinical symptoms.The therapy of reinforcing earth to generate metal for the treatment of stable COPD has good clinical efficacy and safety,and has great potential therapeutic value.Part ? A multicenter,randomized,double-blind,placebo-controlled clinical trial of Jianpi Yifei ? in the treatment of moderate to very severe COPDObjective We aim to observe the long-term clinical efficacy of Jianpi Yifei ? granule in the treatment of patients with COPD at stable stage,and provide high-level evidence-based for the prevention and treatment of COPD with TCM.Methods A national multicenter,randomized,double-blind,placebo-controlled clinical trial design was adopted.Patients with moderate to very severe COPD in stable stage were randomly divided into two groups.The treatment group was given Jianpi Yifei ? granules,while the control group was given Jianpi Yifei ? placebo granules.The induction period was two weeks.the central randomization allocation operation was completed,the patients took one dose daily for five days in a week,and lasted for 52 weeks.We assessed the changes of the SGRQ score,frequency of acute exacerbations,lung function,6-minute walking distance,CAT score,BODE index and the safety of the two groups.Results 1.Enrollment and completion: a total of 284 patients with moderate to very severe COPD in stable stage were enrolled in 6 centers in different regions of China,and 276 cases were actually completed,with the completion rate of 97.18%.A total of 276 patients were included in the full analysis set(FAS),138 each in the treatment group and the placebo group,including 18 cases drop-out in the treatment group and 19 cases drop-out in the placebo group.A total of 284 patients were included in the safety set(SS),142 each in the treatment group and the placebo group.2.Baseline analysis: there was no significant difference in general demographic characteristics,disease characteristics,severity and TCM syndromes between the two groups(P > 0.05).3.Evaluation of quality of life: Fas results showed that compared with placebo,Jianpi Yifei ? granule significantly reduced the SGRQ score of Visit 4 and Visit 6(P < 0.05).The last observation carried forward(LOCF)method was used to fill in the missing data.The results showed that compared with placebo,Jianpi Yifei ? granule significantly reduced the SGRQ score of Visit 4 and Visit 6(P < 0.05).The results suggest that Jianpi Yifei ? granule can improve the quality of life of patients with COPD,and the curative effect is better than that of placebo.4.Evaluation of acute exacerbation of COPD: Fas results showed that compared with placebo,Jianpi Yifei ? granule significantly reduced the frequency of acute exacerbation(P < 0.01),reduced the incidence and severity of acute exacerbation(P < 0.05),and prolonged the time of first acute exacerbation(P < 0.01).The results suggest that Jianpi Yifei ? granule can reduce the frequency of acute exacerbation,prolonged the time of first acute exacerbation,reduce the rate and the severity of acute exacerbation in patients with COPD,and the curative effect is better than that of placebo.5.Evaluation of clinical symptom: Fas results showed that compared with placebo,Jianpi Yifei ? granule could significantly reduce the CAT score of Visit 4 and Visit 6(P < 0.05).The results suggest that Jianpi Yifei ? granule can improve the clinical symptoms in patients with COPD,and the curative effect is better than that of placebo.6.Evaluation of exercise endurance: FAS results showed that compared with placebo,Jianpi Yifei ? granule increased the six-minute walking distance of Visit 4 and Visit 6(P < 0.05).The results suggest that Jianpi Yifei ? granule can increase the exercise endurance in patients with COPD,and the curative effect is better than that of placebo.7.Evaluation of BODE index and Sp O2: Fas results showed that there was no significant difference in BODE index and Sp O2 between the treatment group and the placebo group at different visit time points(P > 0.05).The results suggest that Jianpi Yifei ? granule is not better than placebo in improving BODE index and Sp O2.8.Evaluation of pulmonary function changes: the results of Fas were as follows:(1)Compared with the changes of pulmonary function before using bronchodilators: compared with placebo,Jianpi Yifei ? granule was better than placebo treatment in improving FVC(L)of Visit 4(P < 0.05),but there was no significant difference in other visit time points(P > 0.05).There was no significant difference in FEV1(L),FEV1(%)and FVC(%)between the two groups at different visit time points(P > 0.05).Jianpi Yifei ? granule was not superior to placebo treatment.(2)Compared with the changes of pulmonary function after using bronchodilators: there was no significant difference in FEV1(L),FEV1(%),FVC(L)and FVC(%)between the two groups at different visit time points(P > 0.05).Jianpi Yifei ? granule was not better than placebo treatment.The results suggest that Jianpi Yifei ? granule is not better than placebo in improving pulmonary function before and after using bronchodilators.9.Safety evaluation: SS results showed that t there was no significant difference between Jianpi Yifei ? granules and placebo in the frequency and number of adverse events,the number of serious adverse events,the number of adverse reactions and serious adverse reactions.The results suggest that oral Jianfei granule is safe.Conclusion Jianpi Yifei ? granules significantly improve the quality of life of patients with moderate to very severe COPD,increase exercise endurance,reduce clinical symptoms and acute exacerbation,and it has good safety.