Clinical Study And Systematic Review Of Warming Lung To Nourishing Kidney And Dispelling Wind On Patients With Cough Variant Asthma

Cough variant asthma(CVA)is the main symptom of slow cough.It is a common and frequently occurring disease of the respiratory system.Epidemiology shows that the incidence of CVA is increasing year by year,which seriously threatens patients’health and quality of life.At present,although glucocorticoid and bronchodilator in western medicine are effective,they need to be taken for a long time.There are many side effects,and they are easy to recur after withdrawal.The method of warming the lung and invigorating the kidney and dispelling wind has potential advantages in improving the cough symptoms,improving the immune function and reducing the recurrence of CVA.However,due to insufficient evidence of clinical efficacy and safety,it is difficult to make relevant clinical decisions.Oxford Evidence-based Medicine Center(ECM)takes systematic evaluation and randomized controlled trials(RCT)as the best sources of evidence for recommendation of medical guidelines and clinical practice,so it is necessary to use RCT and systematic evaluation to provide evidence for the efficacy and safety of traditional Chinese medicine in the treatment of CVA.This thesis is divided into two parts:the first part is the systematic evaluation of CVA treated by Wenfei Bushenfeng method;the second part is the clinical study of Xianqi Qinglong Decoction in the treatment of CVA.Fi rst,systematic reviewObjectiveTo systematically evaluate the efficacy,safety and quality of evidence of warming lung,tonifying kidney and removing wind in the treatment of CVA,and to provide evidence for further clinical research on warming lung,tonifying kidney and removing wind in the treatment of CVA.MethodsThe electronic databases PubMed,EMBASE,The Cochrane Library,China Biomedical Literature Database,China National Knowledge Infrastructure,Wanfang Database,and Chongqing Weipu Database were searched systematically.Randomized controlled clinical trial(RCT)articles published on July 15,2018 were selected from the databases established by each database.The RCT of CVA was compared with traditional Chinese medicine.Main Outcome Measures:Cough symptom score;Secondary Outcome Measures:Clinical efficacy,Eosinophil(EOS),immunoglobulin(IgE),recurrence rate and adverse reactions.The methodological quality of the literature was evaluated according to the Cochrane system evaluation manual.Revman 5.3 software was used for data integration analysis.TSA software(0.9.5.10 beta)was used for sequential analysis to calculate the actual sample size of meta-analysis.GRADEpro(3.6.1)was used for evidence quality evaluation.ResultsA total of 13023 literatures were retrieved according to the retrieval strategy.Five studies involving 456 subjects were selected and the overall quality of all methodological evaluations included in the study was low.Meta-analysis:1.Main outcome measures:Cough symptom score:The effect of Wenfei Bushen Qufeng method on reducing the score of cough symptom in CVA patients is better than that of Western medicine ICS(MD=-0.84,95%CI[-1.04,-0.64]).The quality of evidence is low.2.Secondary outcome measures:①Efficiency:The efficacy of Wenfei Bushen Qufeng method was higher than that of Western medicine(RR=1.12,95%CI[1.02,1.22]).TSA results supported the meta-analysis,and the quality of evidence was intermediate;②EOS:There was no significant difference in EOS reduction between the traditional Chinese medicine and Western medicine(MD=-0.02,95%CI[-0.07,0.03]),and the quality of evidence was low;③IgE:There was no significant difference in the effect of warming the lung,invigorating the kidney and eliminating wind between the traditional Chinese medicine and Western medicine(MD=-9.50,95%CI[-19.28,0.27]),and the quality of evidence was low;④Recurrence rate:The effect of Wenfei Bushen Qufeng method is better than that of Western medicine in reducing the recurrence rate(RR=0.32,95%CI[0.19,0.55]),the quality of evidence is low;⑤Safety and adverse reactions:1 study reported the safety of the drug;3 studies reported adverse reactions;only 1 study reported 3 cases of mild nausea and gastrointestinal discomfort in traditional Chinese medicine of warming the lung and kidney and eliminating wind;the other two studies reported no adverse reactions.ConclusionWarming the lung,invigorating the kidney and dispelling wind has a good clinical effect in improving cough symptoms,improving clinical efficiency,reducing inflammatory indexes(EOS,IgE),and reducing recurrence in CVA patients,with fewer adverse reactions and good safety.However,due to the limitations of this system,the quality of the evidence obtained is not high,so it can not be fully affirmed that the method of warming the lung,invigorating the kidney and dispelling wind on CVA efficacy.More high-quality randomized controlled trials are needed in the future to provide evidence for the efficacy of warming the lung,invigorating the kidney and removing wind in the treatment of CVA.Second,cl inical researchObjectiveTo evaluate the efficacy and safety of Xianqi Qinglong Prescription in treating CVA,a randomized controlled clinical study was conducted to provide new ideas and evidence-based evidence for the differentiation and treatment of CVA.MethodsA randomized controlled clinical study was conducted to select 102 patients with CVA who had deficiency of lung and kidney and stagnation.The patients were divided into treatment group and control group by random number table method.The treatment group was given Xianqi Qinglong granule,and the control group was given placebo combined with Fu Shu Ke and placebo.The two groups were treated for 12 weeks,with a follow-up period of 12 weeks.During the treatment,the safety was observed,and the curative effect was analyzed after 6 weeks,12 weeks and follow-up.(1)Main outcome indicators:Cough symptom score;(2)Secondary outcome indicators:① Cough remission and disappearance days;② Visual analogue scale(VAS);③TCM syndrome score;④Leicester Cough Questionnaire(LCQ);⑤ Eosinophil(EOS);⑥Eosinophilic cationic protein level(ECP);⑦Lung function(FEV1,FEV1%pred,FVC,PEF);⑧Remission rate;⑨Recurrence rate;(3)Safety indicators:blood routine,liver and kidney function,adverse reactions and adverse events.Statistical analysis was performed on the data using SPSS 17.0 software.ResultsA total of 102 cases were included in this study.One case was excluded and 7 cases were shedding.101 cases were included in the fill analysis set analysis,and 94 cases were included in the per-protocol analysis set.The demographic data,test-related data,and experimental analysis data of the two groups of patients were comparable(P>0.05).(1)Main outcome indicatorsThe total score of cough symptoms,daytime and night cough symptoms in the two groups decreased after 6,12 weeks of treatment and follow-up(P<0.01);there was no significant difference between the two groups at any time point(P>0.05).The non-inferiority test showed that 95%of the total scores of cough symptoms at 6,12 and follow-up weeks were higher than the non-inferiority threshold of-0.6,and the non-inferiority results were valid.(2)Secondary outcome indicators:①The days of remission and disappearance of cough in the two groups were increased at 12 weeks after treatment(P<0.05).②There was no significant difference between the two groups at each time point(P>0.05).The VAS score,TCM score and LCQ total score of the two groups were lower than those before treatment at 6 weeks,12 weeks and after follow-up(P<0.05).There was no statistical difference between the two groups at each time point.Academic significance(P>0.05).③There was no significant difference in ECP and EOS between the two groups(P>0.05).④The lung function PEF of the two groups increased after 12 weeks of treatment and follow-up(P<0.05).There was no significant difference between the two groups(P>0.05).There was no significant difference in lung function FEV1,FEV1%pred and FVC between the two groups(P>0.05).⑤There was no significant difference in the rate of cough remission between the two groups at 6 weeks and 12 weeks(P>0.05).⑥There was no significant difference in the recurrence rate of cough between the two groups at 6 weeks and 12 weeks(P>0.05).The recurrence rate of cough in the treatment group was lower than that in the control group(P<0.05).(3)safety evaluationThe liver and kidney function of the two groups were in the normal range before and after treatment.The blood routine results showed that the platelet increased slightly in 5 patients after treatment,suggesting no clinical significance.Adverse reactions:During the course of treatment,the blood routine,liver and kidney function of the two groups were in the normal range.Adverse reactions:There were 4 adverse reactions in the two groups during the treatment.One patient in the treatment group had an adverse reaction to sore throat and dry mouth.Considering the possibility of treatment and treatment,no treatment,the symptoms were relieved after diet conditioning.The patients in the control group developed adverse reactions in 3 cases,1 case was nausea,the degree was mild,and the treatment was not affected.2 cases were pharyngeal discomfort,and the degree was mild.The patient refused to continue taking the medicine and withdrew from the test.Adverse events:The relationship between adverse events and interventions in the two groups was judged to be irrelevant;neither group had serious adverse events during the treatment.Conclus ionXianqi Qinglong Recipe can effectively alleviate cough symptoms in patients with CVA,and has better curative effect in improving TCM syndrome,improving quality of life,improving pulmonary function PEF,and improving remission rate.The advantages are obvious,and the adverse reactions are few,the safety is good,and the effectiveness of the Wenfei kidney-reinforcing method is verified.This study can not prove the effect of Xianqi Qinglong Recipe on improving lung function(FEV1、FEV1%pred,FVC),but there is a certain trend,which needs to be verified by a larger sample size.The improvement of inflammation index(EOS,ECP)is not obvious.Considering that some patients are in the normal range,further objective indexes such as serum IgE,induced sputum eosinophil count,inflammatory factor IL-4 can be used to explore the possible mechanism of Xianqi Qinglong Recipe.