The Clinical Efficacy In Wind-Heat Syndrome Of Refractory Chronic Urticaria By Modified Xiao Feng Powder And Its Effect On Intestinal Flora

Objective:To inherit and optimize the experience of famous veteran doctors of traditional Chinese medicine,and observe the clinical efficacy and safety of Modified Xiaofeng Powder in the treatment of wind-heat syndrome of refractory chronic urticaria.To investigate the effect of dysregulation of the gut microbiota on the therapeutic effect of refractory chronic urticaria,and to explore the mechanism of Modified Xiaofeng Powder in the treatment of refractory chronic urticaria from the perspective of lung-gut comorbidities.Methods:This study carried out a randomized controlled clinical,taking Professor Zhu Renkang’s prescription of Liangxue Xiaofeng Powder as the control group.A total 60 patients with refractory chronic urticaria with wind-heat syndrome from the outpatient department of dermatology of Guang ’anmen Hospital were involved.Using the randomized digital table method,all the subjects were randomly divided into two groups:A(eliminating wind)group(n=30)and B(modified eliminating wind)group(n= 30).A group was treated with Liangxue Xiaofeng Powder combined with cetirizine hydrochloride tablet 10mg Qn for 4 weeks.B group was treated with Modified Xiaofeng Powder combined with cetirizine hydrochloride tablet 10mg Qn for 4 weeks.The clinical efficacy of before and after treatment was compared between the two groups.Observation indexes included:1)Efficacy index evaluation of SSRI;2)Disease severity evaluation(wheal severity score HSS,pruritus severity score ISS,urticaria activity score UAS,urticaria activity score over 7 days UAS7;3)wheal regression time;4)Total dose of antihistamine used(weeks).Fecal samples were collected from all subjects at the beginning of treatment and the end of 4 weeks of treatment.16S rRNA sequencing was used to analyze the microbial diversity of fecal samples between the two groups before and after treatment,and the diversity,composition,abundance and homogeneity of fecal microbiota were compared.Microbial classification and differences between groups(family level,class level,order level,family level,genus level)were compared,then using the database Greengene to compare species annotation.Statistical methods were used to compare the differences between groups.Results:In this study,a total of 48 patients with refractory chronic urticaria with wind-heat syndrome were included.There were 23 cases in A aroup and 25 cases in B aroup.There were no statistically significant differences in the baseline data of gender,total disease duration,time of onset,urticaria severity score(UAS score,UAS7 score,HSS score,ISS score),wheal regression time and total dose of antihistamine used(weeks)between the two groups,but there was statistically significant difference in age.Due to age difference,multivariate linear regression analysis using baseline UAS7 score as the outcome variable confirmed that there was no correlation between age and baseline UAS7 score,so the baselines were comparable.After 4 weeks of treatment,both modified Xiaofeng powder and Liangxue Xiaofeng powder showed good therapeutic effects(total effective rate 84%vs 91%,recovery rate 64%vs 52%),and the efficacy of the two groups was similar(P>0.05).Modified Xiaofeng powder and Liangxue Xiaofeng Powder had similar efficacy in lessening the severity of urticaria,and both significantly lessened the UAS score,UAS7 score,HSS score,and ISS score(P<0.0001).Compared with Liangxue Xiaofeng Powder,modified Xiaofeng powder significantly shorten the wheal regression time(P<0.05).Either using a single antihistamine or a dual antihistamine,the total dosage of antihistamines was reduced in both groups(P<0.05),but there was no significant difference in the total dosage reduction between the two groups(P>0.05).In terms of safety,no serious adverse events occurred in the two groups.Only mild leukocyte elevation occurred in 2 patients in the A group,which did not affect the clinical efficacy of patients.Microbial diversity analysis showed that although both modified Xiaofeng Powder and Liangxue Xiaofeng powder could affect the diversity of intestinal flora(P<0.05),different formulations of Xiaofeng powder had different regulatory effects on intestinal flora.After treatment with Modified Xiaofeng Powder,the species diversity of intestinal flora of patients was higher(P<0.05).Modified Xiaofeng powder could increase the abundance of different species of intestinal flora(P<0.05),and different formulations of Xiaofeng powder could play different intestinal regulation roles by regulating the abundance of specific species of intestinal flora.For example,Liangxue Xiaofeng Powder could unidirectionally down-regulate Lachnoclostridium and Butyricicocus(P<0.05);Modified Xiaofeng Powder has the function of bidirectionally regulation,which up-regulate the expression of Raoultella and Citrobacter as well as down-regulate the expression of Butyricicocus(P<0.05).Raoultella and Citrobacter are colonized bacteria in the intestinal tract,which are involved in maintaining the stability of intestinal flora.Modified Xiaofeng powder may improve the colonization homeostasis of intestinal flora by up-regulating the expression of Raoultella and Citrobacter,thereby inhibiting the activation of downstream immune pathways by intestinal pathogens.In addition,both Liangxue Xiaofeng Powder and Modified Xiaofeng Powder could significantly down-regulate the expression of Butyricicocus,suggesting that different components of Xiaofeng powder may play an immunomodulatory role through the same genus.Conclusion:Refractory chronic urticaria has a long course and is prone to relapse,and is resistant to conventional antihistamines,which seriously affects the quality of life of patients.Based on the theory of "lung and large intestine being interior-exteriorly correlated",the formula of famous veteran doctor-Liangxue Xiaofeng Powder was modified to Modified Xiaofeng Powder,which is beneficial to to strengthen the lung and the skin through regulating the function of the spleen and stomach,unobstructed the intestine and dispelling the wind.Studies have shown that Modified Xiaofeng Powder and Liangxue Xiaofeng Powder can effectively improve the clinical symptoms of refractory chronic urticaria,reduce the dosage of antihistamines,and have a good clinical efficacy and safety.Modified Xiaofeng Powder can also shorten the wheal regression time.Its possible mechanism is up-regulate the diversity of intestinal flora,bidirectionally regulate the abundance of specific intestinal bacteria to improve the homeostasis of intestinal flora colonization,which play the role of "Lung-intestinal simultaneous regulation".