Literature And Mechanism Research On The Treatment Of Cough Variant Asthma In Children Based On Sputum Based On The Balance Of Th1/Th2 Cell Functio

Objective:To conduct a meta-analysis of randomized controlled clinical trials for the treatment of cough variant asthma(CVA)using Erchen Decoction,based on the theory of phlegm-based treatment.The objective of this study is to provide evidence-based medicine for its treatment and clinical efficacy,to provide a reference treatment method and theoretical basis for the clinical treatment of CVA.Simultaneously,through the changes of serological and histological indicators in animal experiments,we will explore whether Jiawei Liuan Decoction affects the differentiation of downstream Tlymphocytes through the regulation of the Notch signaling pathway ligand-proteins in lung tissues.Thereby regulating the balance between Th1/Th2 cells,mediating the release of cytokines,and improving chronic airway inflammation.To provide an experimental basis for the establishment of a treatment approach of CVA.Methods:1.Randomized controlled clinical trials involving Erchen Decoction as the basic prescription for the treatment of CVA that have been publishedwere comprehensively searched.Literature screening and data extraction were then carried out.The Cochrane systematic evaluation method was applied to conduct a meta-analysis on the clinical efficacy,TCM syndrome efficacy,cough symptoms scores,sputum symptom scores,lung function index first second of forced expiratory volume(F EV1),lung function index peak expiratory flow(PEF),serum immunoglobulin E(IgE)content,as wellas the recurrence rate during follow-up.2.①Thirty 3-week-old male healthy specific-pathogen-free(SPF)Hartley guinea pigs(body weight varying between 230-280 g)were randomly divided into three groups.The optimal CVA guinea pig modeling method was determined using three different modeling methods based on preliminary experiments.②Sixty 3-week-old male healthy SPF Hartley guinea pigs(body weight varying between 230-280 g)were randomly divided into blank control group,model group,montelukast sodium group,and Jiawei Liuan decoction group(low,medium,and high dose),with 10 guinea pigs in each group,and adaptative feeding conducted for 3 days.Except for the blank control group,the immunosuppressant cyclophosphamide(30 mg/kg dosage)was injected intraperitoneally on the first day,and each guinea pig was injected with 1 mL of a suspension of 2 mg ovalbumin(OVA)and 200 mg aluminum hydroxide on the third day.Intraperitoneal injection of a suspension of O.1mg OVA and 100mg aluminum hydroxide was performed on the 22nd day to strengthen the immune response.1%OVA solution was used for atomization from the 23rd day onwards,once every other day,for a total of 7 times.The normal control group was administered with the same dose of saline.The number of coughs in each group of guinea pigs was observed and recorded.Secondly,the number of coughs in each group after capsaicin stimulation was observed and recorded.Next,the effect of methacholine challenge(MeCh)on airway resistance in each group of guinea pigs was observed and recorded.Next,chronic inflammation and infiltration of the guinea pig airway were observed through hematoxylin-eos in(HE)staining.Enzyme-linked immunoassay(ELISA)was used to detect the levels of IL-2,IL-4,IL-12,and IL-13 in the guinea pig serum and bronchoalveolar lavage fluid(BALF)of each group.The Delta,Jaggedl,Notchl,and NICD proteins in the lung tissue of each group were detected using Western blot.Results:1.Among the 18 studies included,treatment of children’s CVA using solely modified Erchen Decoction or in combination with Western medicine showed better clinical efficacy and improved TCM syndrome compared to pharmaceutical trea tment alone,particularly in the domains of cough scores and sputum scores.It is also superior to pharmaceutical treatment in improving lung function index FEV1 and reducing IgE levels in children,but both showed equivalent effects in the improvement of PEF.Comparedwith pharmaceutical treatment,the recurrence rate of modified Erchen Decoction alone or in combination with Western medicine was lower,and thedifference was statistically significant.In terms of adverse reactions,11 studies reported adverse reactions,of which 5 studies reported no apparent adverse reactions during treatment,and the remaining 6 reported controllable adverse reactions.There was no significant difference in the incidence of adverse reactions between both groups(P>0.05).2.Compared with the blank control group[(1.80±0.58)times](physiologica 1 saline spray stimulation),the number of coughs in the model group[(11.00±1.48)times]and the montelukast sodium group[(6.40±1.29)times],the low-dose Jiawei Liuan decoction low-dose group[(4.40±0.93)times],the medium-dose Jiawei Liuan Decoction group[(5.00 ± 1.38)times],and the high-dose Jiawei Liu an Decoction group[(5.00±1.14)times]were significantly increased,and the difference was statistically significant(P<0.05).Compared with the model group,the number of coughs in each dose group of Jiawei Liu’an Decoction and the Mont elukast sodium group was reduced,with statistical difference(P<0.05).Among them,the low-dose group of Jiawei Liuan Decoction had the least number of coughs.Compared with the montelukast sodium group,the number of coughs in each dose group of Jiawei Liuan Decoction decreased.However,therewas no significant difference in the number of coughs in the other drug intervention groups(P>0.05).Compared with the blank control group,the airway resistance of the other five groups was different and statistically significant at normal saline,MeCh0.02,and 0.04mg/mL dosage levels(P<0.05).There were statistically significant differences in airway resistance after methacholine challenge at MeCh0.02mg/mL dosage between the low andhigh-dose decoction groups compared with the model group.The airway resistance of the blank control group and the low-dose and middle-dose Liuan decoction group gradually increased with the increase in challenge concentration,while the airway resistance of the model group,the montelukast sodium group,and the high-dose Jiawei Liuan decoction group peaked at MeCh0.04mg/mL dosage.The lung tissue pathologicalinflammation scores between the blank control group and the other five groups were statistically significant,and the difference between the low-doseJiawei Liuan decoction and the model group was statistically significant(P<0.05).3.ELISA test results:The levels of serum cytokines in CVA guinea pigs and the levels of IL-13 in the montelukast sodium group and the Jiawei Liuan decoction group were lower than the model group,and the IL-12、IL-2、IL-4 contents were higher than the model group.The content of IL-12 was significantly different between the montelukast sodium group and the low,medium,and high-dose Jia wei Liuan Decoction groups and themodel group.There was no significant difference between the low dose ofthe Jiawei Liuan Decoction group and the model group.There was no statistically significant difference in IL-13 content between each group and the model group.Among the cytokines in the BALF,the levels of IL-2,IL-12 in the montelukast sodium group and the various dose groups of Jiawei Liuan Decoction were higher than those of the model group.Among them,the higher the concentration of Jiawei Liuan Decoction,the more significant the difference in the contents of IL-2 and IL-4.The content of IL-13 in the low-dose Jia wei Liuan Decoction group decreased significantly after treatment compared with the model group(P<0.05),but there was no statistically significant difference betw een the high-dose group and the model group.4.Western blot detection results:Compared with the normal group,the expression of Notch ligand-protein Delta1 in the other five groups was significantly reduced,while the expressions of ligand Jagged1,receptor Notchl,and Notch prote in fragment NICD with nuclear localization were significantly increased,and the difference was statistically significant.The expression levels of Jagged1,Notch1,and NICD proteins in the montelukast sodium group and low-dose Jiawei Liuan decoction group decreased compared with the model group,and the expression of the Delta1 protein increased(P<0.05).However,the difference was not statistically significant between the two groups.The protein contents of the middle and high-dose Jiawei Liuan group were not statistically different from that of the model group.conclusion:1.Treatment of children’s CVA using modified Erchen Decoction has proved to be more superior than pharmaceutical treatment in terms of total clinical efficacy and TCM syndrome improvement,particularly in the domains of cough and sputum,improvement of lung function index FEV1,and reduction of IgE levels in children.However,both treatment modalities are equivalent in terms of the improvement of PEF.Concurrently,the recurrence rate of modified Erchen Decoction alone or in combination with Western medicine was lower.This has certified the precision and rationality of the clinical treatment of children’s cough variant asthma based on phlegm.2.All dose groups of the Jiawei Liuan Decoction and monte lukast sodium group showed equivalent effects in reducing airway sensitivity in CVA guinea pigs.All dose groups of the Jiawei Liuan Decoction and montelukast sodium group are effective in reducing airway hyperresponsiveness in CVA guinea pigs.The high-dose Jiawei Liuan Decoction group which showed the most apparent effects.After treatment with Jiawei Liuan Decoction and montelukast sodium,the lung tissue pathological inflammation scores in the CVA guinea pigs decreased.The low-dose Jiawei Liu’an Decoction group showed better effects compared to the montelukast sodium group.3.Jiawei Liuan Decoction can increase the IL-2 serum content,down-regulate the IL-4 content,up-regulate the IL-2 and IL-12 contents in BALF,down-regulate the IL-13 content,and adjust the dynamic balance between Th1/Th2 cells.This reduces chronic airway inflammation and thereby achieving the treatment purpose.4.Jiawei Liuan Decoction can increase the expression of Delta1 protein and inhibit the expression of Jagged1,Notch1 and NICD proteins.Thereby regulating the differentiation of T lymphocytes in the lung tissue,regulating the balance between Th1/Th2 cells,affecting the release of cytokines,and reducing chronic airway inflammation.Besides,the effect of the low-dose Jiawei Liuan Decoction group is the best among all drug interventiongroups.