A Randomized Controlled Study Of Qingbu Weijing Decoction In The Treatment Of Airway Mucus Hypersecretion In Stable Bronchiectasis

Bronchiectasis is a common chronic respiratory condition chiefly manifested by a persistent cough that produces sputum.Increased sputum production and recurrent acute exacerbations may also occur.Being recognized as a basic pathophysiological and clinical feature of bronchiectasis,airway mucus hypersecretion,which is correlated with the severity of airway inflammation and injury in patients with bronchiectasis,will result in worsening lung function,increased risk of hospitalization,poor prognosis,and increased risk of death,seriously affecting the quality of life of patients with bronchiectasis.Expert Consensus on the Diagnosis and Treatment of Adult Bronchiectasis in China suggested the importance of expectorant treatment in the stable stage of bronchiectasis to reduce the frequency of acute exacerbations.Airway mucus hypersecretion is usually understood in the perspective of"phlegm-fluid retention" in traditional Chinese medicine(TCM),which by providing abundant phlegm-eliminating methods,throws light on the treatment of airway mucus hypersecretion.Therefore,it has been an important research topic to foster the study of TCM treatment of airway mucus hypersecretion,especially in the long-term intervention of the stable stage of bronchiectasis,improving the quality of life of patients with bronchiectasis,and decreasing the recurrence of the disease.This study is divided into two parts.The first part entails a literature research which using a scoping review approach,systematically examined the clinical research evidence for TCM treatment of the stable stage of bronchiectasis to comprehensively understand the current situation of relevant research fields,as well as summarized pattern type,formula selection,medication,outcome indicators and others of concern in clinical research,and presented the research results through a combination of graphics and text.The second part involves a clinical study where the efficacy and safety of the methods of benefiting qi,nourishing yin,clearing heat,and resolving phlegm were observed in improving airway mucus hypersecretion in patients with the stable stage of bronchiectasis by a randomized controlled trial(RCT).PART1.A scoping review on TCM treatment of the stable stage of bronchiectasisObjective:To systematically search and sort out clinical studies on TCM treatment of the stable stage of bronchiectasis and identify evidence distribution on related topics based on scoping reviews.Methods:A search of 6 most commonly used literature databases were conducted with the inclusion of relevant clinical studies,and visualization analysis was performed to identify the characteristics of studies in this field in terms of intervention formula-medicines,frequency of medication,control and intervention duration,follow-up duration,and outcome indicators,explore the factors that interfere with the efficacy of the stable stage of bronchiectasis,as well as find out the basic information of relevant clinical evidence.Results:The bibliometric analysis showed a limited amount of literature in this field,with an upward trend in the number of publications but poor quality since 2018.A total of 53 papers and documents were included,involving 39 RCTs(including 6 single-case randomized controlled trials and 33 randomized parallel controlled trials)and 14 non-randomized intervention studies.38 of them documented TCM pattern types,incorporating deficiency pattern(predominantly lung and spleen qi deficiency or qi and yin deficiency pattern),excess pattern(predominantly damp phlegm pattern or phlegm heat accumulating in the lung pattern),and combined deficiency and excess pattern(spleen deficiency with phlegm retention or spleen deficiency with phlegm heat pattern).11 interventions were obtained with the highest frequency of the qi-tonifying,qi-tonifying and yin-nourishing as well as lung-clearing and phlegm-resolving methods.The outcome indicators were determined based on efficiency,quality of life,symptoms,lung function,and mechanism.Conclusion:Experience of TCM intervention treatment of the stable stage of bronchiectasis has been accumulated,basically demonstrating its efficacy.However,the quality of evidence needs to be improved.Furthermore,"qi deficiency-phlegm heat" is largely considered the key pathogenesis of the stable stage of bronchiectasis.The present study may shed some light on the design of future studies.PART2.A randomized controlled study of Qingbu Weijing Decoction in the treatment of airway mucus hypersecretion in stable bronchiectasis.Objective:To observe the efficacy and safety of Qingbu Weijing Decoction in improving airway mucus hypersecretion in patients with the stable stage of bronchiectasis.Methods:A group-randomized,positive drug-controlled clinical trial was conducted involving 80 patients with airway mucus hypersecretion in the stable stage of bronchiectasis who were randomly divided into two groups to receive Qingbu Weijing Decoction or Carbocysteine Oral Solution for a period of 12 weeks with a follow-up of 12 months.The frequency of acute exacerbations per year,Cough and Sputum Assessment Questionnaire(CASA-Q),Quantitative Symptom Score(QSS),lung function,serum neutrophil elastase(NE),serum inflammatory factors(TNF-α,IL-8,IL-10),and the Modified Reiff Score were used for evaluation and analysis.Results:1.The frequency of acute exacerbationsThe frequency of acute exacerbations in the observation group was significantly lower than that in the control group with the differences proving to be statistically significant(P<0.05)either after 12 weeks of treatment or at 12 months of follow-up.The frequency of acute exacerbations in the observation group was significantly lower compared to the control group within 12 months of follow-up and before enrollment;the differences reached statistical significance(P<0.05).2.Cough and Sputum Assessment Questionnaire(CASA-Q)Within the intervention and follow-up time points,the COUS,COUI,and PUS scores of the observation group were higher by 14.794(P=0.000),5.436(P=0.000),and 13.164(P=0.000),respectively,comparing with the control group.The SPUS scores at all visit time points were significantly higher than those before treatment(P<0.05);and the SPUI score of the observation group was 8.662 higher than that of the control group(P=0.020).3.Quantitative Symptom Score(QSS)Within the intervention and follow-up time points,the TCM quantitative symptom score in the observation group was lower by 1.362(P=0.005)than that of the control group.Concerning each single symptom,the symptom scores of cough,sputum,chest tightness and shortness of breath,dry mouth,and dry throat in the observation group were significantly lower in comparison with the control group(P<0.05).4.Lung functionFEV1%pred,FVC%pred,and FEV1/FVC were all higher in the observation group after treatment with no statistical significance found(P>0.05).The differences between the two groups before and after treatment didn’t reach statistical significance(P>0.05).In the observation group,an increase of the PEF%pred was found after treatment,indicating statistical significance(P<0.05);and the differences between the two groups before and after treatment reached statistical significance(P<0.05).5.Serum neutrophil elastase(NE)In the observation group,a reduction of the NE level was detected after treatment,indicating statistical significance(P<0.05).However,the differences between the groups after treatment didn’t achieve statistical significance(P>0.05);the differences in the NE levels before and after treatment didn’t show statistical significance(P>0.05).6.Serum inflammatory factorsIn the observation group,reductions of the TNF-α and IL-10 levels were found after treatment,showing statistical significance(P<0.05).However,the differences between the groups after treatment didn’t achieve statistical significance(P>0.05);the differences in the TNF-α and IL-10 levels before and after treatment were not statistically significant(P>0.05).A decrease of the IL-8 level was also detected following treatment,indicating statistical significance(P<0.05);the differences between the groups after treatment were statistically significant(P<0.05);the differences in the IL-8 levels before and after treatment also showed statistical significance(P<0.05).7.The Modified Reiff ScoreNo significant changes were seen in the modified Reiff scores before and after treatment in the two groups,with no statistical significance found within the group before and after treatment,or between the groups after treatment or before and after treatment(P>0.05).Conclusion1.Qingbu Weijing Decoction is helpful to reduce the frequency of acute exacerbations in patients with the stable stage of bronchiectasis,improve CASA-Q scores,reduce sputum characteristic scores,and improve patients’ quality of life by suggesting the reduction of airway mucus hypersecretion.2.Qingbu Weijing Decoction can partially enhance lung function(by PEF%pred)and tends to reduce the levels of serum inflammatory factors(predominantly IL-8)and NE levels in patients with bronchiectasis,with no significant adverse effects observed.