Study On The Clinical Effect And Mechanism Of Kemin Qidan Nasal Spray During The "Sanjiu Period" In The Prevention And Treatment Of Perennial Allergic Rhinitis

Objective Based on the tutor's understanding of the core pathogenesis of " Qi Deficiency of Lung and Spleen,blood stasis in nasal orifices " in rhinorrhea(Perennial allergic rhinitis)and On the remarkable clinical effect in the early 20 years,Through the method of the external treatment with traditional Chinese medicine to treat the Perennial allergic rhinitis(PAR)of the Syndrome with Qi Deficiency of Lung and Spleen.To evaluate the clinical efficacy of Kemin Qidan nasal spray in “Sanjiu” solar term and follow up its long-term efficacy,as well as to investigate its changes of the mechanism of Tbet/GATA–3 and IFN-?/IL–4,and aim to provide the evidence-based basis and exploring the new ideas of the mechanism of action for the clinical application by Kemin Qidan nasal spray to prevent and treat the perennial allergic rhinitis.MethodsIn this study,patients with perennial allergic rhinitis(Qi Deficiency of Lung and Spleen)were collected as the research object during the “Sanjiu” solar term in December 2019 in chengdu university of traditional Chinese medicine hospital.The random single blind controlled study design of clinical trials.Strict inclusion and exclusion criteria have been established.Using the computer random way,with aid of EXCEL software,and the RAND function to generate random Numberation table.60 patients were divided into three groups,that is the group of A(the treatment group),the group of B(the control group)and the group of C(the placebo group),with 20 cases in each group.This study has passed the ethical review and approval of the Medical Ethics Committee of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine and the approval number is: 2019KL-068.The treatment group was treated with Kemin Qidan nasal spray,2 sprays on each side of nostril,3 times a day.The control group was given momethasone furoate nasal spray,twice for each side of nostril,once a day.And the placebo group was given 10% Kemin Qidan nasal spray,two sprays on each side of nostril,3 times a day.Each group was treated for 27 days.The Nasal Symptoms Scale,Signs Scale,Chinese Medicine Syndrome Scale and Rhinoconjunctivitis Quality of Life Questionnaire of the patients were recorded before and after the treatment,3months and 6 months after the treatment as a subjective evaluation index to evaluate the clinical efficacy and long-term efficacy of Kemin Qidan nasal spray in the treatment of this disease.Outcomes including the Serological indexes sIgE,IFN-?,IL-4,GATA3,T-bet before treatment,27 days after treatment and 3 months follow-up and The nasal endoscopic and The Nasal secretion smear before treatment,27 days after treatment as objective indexes To explore the therapeutic mechanism of Kemin Qidan nasal spray in the treatment of this disease.During treatment,the adverse reactions of subjects will be recorded in detail.Results1.Baseline: Comparison of gender,age and disease course distribution of subjects in the three groups before treatment showed no statistically significant(P>0.05),and all baselines were comparable.2.Score evaluation of nasal symptoms and signs:(1)Before treatment,there was no significant difference in nasal symptoms and signs among the three groups(P>0.05),which could be used to compare the treatment effect.(2)There were differences among the three groups after 27 days of treatment,at the follow-up of the third month and the sixth month(P<0.05).(3)After 27 days of treatment and 3 months of followup,the P values between group A and group B were greater than 0.05 by Multiple comparison test of one-way ANOVA and Kruskal-Wallistest test.After 27 days of treatment and 3 months of follow-up compared with those before treatment.While The P values of group A and group B were all less than 0.05 after 27 days of treatment and at the third month of follow-up compared with those before treatment,indicating that the symptoms,signs and total scores of symptoms and signs of PAR patients were effectively improved in both the treatment group and the control group after treatment,and the efficacy of both groups was similar,and both had the effect of preventing recurrence.While the group C compared with group A and group B,the P values were all less than 0.05,indicating that the placebo group was lower than the treatment group and the control group in terms of efficacy and prevention of recurrence.(4)Comparison among the three groups at the 6th month follow-up showed that the P value of group A was less than 0.05 compared with that of group B and group C,and the P value of group A was less than 0.05 compared with that of the pre-treatment group at the 6th month follow-up,indicating that the long-term efficacy of the treatment group in controlling the symptoms and signs of PAR patients was better than that of the control group and the placebo group.3.Evaluation of TCM syndromes:(1)There was no statistical significance between the three groups before treatment(P > 0.05),which was comparable.After the treatment,the third month of follow-up and the sixth month of follow-up have differences(P<0.05).It indicated that there were differences in TCM syndromes among the three groups.(2)After 27 days of treatment and the 6th month of follow-up were used the multiple comparisons by one-way analysis and the Kruskal-Wallis test was used at the3 rd month of follow-up.The P values of group A compared with the group B and C were all less than 0.05,and P value of group A was less than 0.05 compared with that of the pre-treatment group,This indicates that the treatment group is better than the control group and the placebo group in improving the TCM syndrome of PAR with the Syndrome of Qi Deficiency of Lung and Spleen,and the treatment group is better than the control group and the placebo group in preventing recurrence and long-term efficacy.4.RQLQ score evaluation:(1)Comparison of RQLQ scores among the three groups before treatment showed that the P values were greater than 0.05,indicating that the three groups were comparable.(2)The P values of the three groups were all less than0.05 after 27 days of treatment,the third month of follow-up and the sixth month of follow-up,indicating that there were differences among the three groups.(3)One-way analysis of variance was used for multiple comparisons with After 27 days of treatment and the follow-up at 3 months,The P values of the scores of activity,sleep,the actual problem,nasal symptoms,ocular symptoms and emotional and the total score of quality of life in group A and group B was no statisticals.while Group C compared with group A and group B,its P value is less than 0.05.but in the treatment after 27 days,at the time of 3 months follow-up,compared with before treatment,the Quality of life has improved and the results were statistically different(P < 0.05),suggesting that the treatment group and control group all can improve the quality of life in patients with AR,and prevent its recurrence,placebo groups to improve patient's quality of life and prevent the recurrence of poor effect in treatment group and control group.While the scores of non-nasal / ocular symptom items in group A were less 0.05 compared with those in groups B and C,indicating that the treatment group was superior to the control group and placebo group in improving the scores of non-nasal / ocular symptom items.(4)At the 6th month follow-up,the P value of group A was less than 0.05 compared with that of group B and C,and the P value of group A was less than 0.05 compared with that of the pre-treatment group at the 6th month follow-up,indicating that the longterm efficacy of the treatment group in improving the quality of life of PAR patients was better than that of the control group and the placebo group.5.Serological index evaluation:(1)The tested values between groups of Serological parameters of IL-4,IFN-?,sIgE,GATA3 and T-bet were compared among the three groups before treatment.There was no statistically significant(P>0.05),indicating that the serological indexes of the three groups were comparable.(2)After 27 days of treatment and at the follow-up of 3 months,the difference between the detected values of serological indicators and the pre-treatment values(difference 1 and difference 2)was all lower than 0.05,indicating that the serological indexes of the three groups were different.The P values of difference 1 and difference 2 of serum indexes IL-4,IFN-?,sIgE,GATA3 and T-bet between group A and group B were greater than 0.05.and Comparison of P values in group A and group B after 27 days of treatment and at the follow-up of 3 months compared with before treatment was all less than 0.05.the results suggest that the treatment group and control group can effectively improve the serological indexes of subjects which inhibit the serum indexes of IL-4,sIgE and GATA3 and promote the level of IFN-? and T-bet in PAR patients.And it has the effect of preventing recurrence.The comparison of group C with group A and group B indicated that the placebo group was less effective than the treatment group and the control group in improving the content of serological indexes of PAR subjects and preventing recurrence(P<0.05).6.Evaluation of nasal secretions smear: a large number of eosinophil cells(EOS) could be seen under the microscope of HE staining in the three groups of nasal secretion smear before treatment,which were comparable.After 27 days of treatment,the amount of EOS in nasal secretions smear of group A and group B was significantly reduced by HE staining under microscope.However,the amount of EOS in nasal secretions smear of group C was not significantly reduced by HE staining under microscope.The results indicated that both the treatment group and the control group could inhibit the secretion of eosinophils in nasal cavity.7.Overall efficacy evaluation:(1)The clinical effective rate in the treatment group was85%,the clinical effective rate in the control group was 94.7%,and the effective rate in the placebo group was 50%.Comparison between groups indicates that the three groups were different(P=0.004<0.01).(2)The comparison between group A and group B,the value of P was 0.636,which greater than 0.05,have no statistical differences,When group A and group B is compared with group C,the result indicates that the curative effect of the group C is lower then the group A and the group B(P< 0.05).indicates that the treatment group had the same curative effect as the control group.8.Adverse reactions: There was no nasal discomfort in Group A during the treatment;In group B,there were 2 cases showed obvious nasal dryness and 2 cases showed bleeding in the nose.In group C,there was 1 case developed nasal dryness and 1 case felt nasal discomfort.No other serious adverse events occurred during the whole treatment process.Conclusions1.The clinical symptoms,signs and quality of life of patients with perennial allergic rhinitis of the Syndrome of Qi Deficiency of Lung and Spleen were effectively improved by the treatment of Kemin Qidan nasal spray and Momethasone furoate nasal spray during the "Sanjiu" solar term,and the efficacy of both was equivalent.2.Patients with perennial allergic rhinitis with Qi deficiency of lung and spleen were treated with Kemin Qidan nasal spray during the "Sanjiu" solar term,which can effectively improve the TCM syndrome.3.The long-term efficacy of perennial allergic rhinitis patients with Qi deficiency of lung and spleen that treated with Kmin Qidan nasal spray is better than mometasone furoate nasal spray and 10% Kmin Qidan nasal spray during the "Sanjiu" solar term,4.In this study,there were no adverse reactions or adverse events found during the treatment and follow-up By Kemin Qidan nasal spray.5.Both Kemin Qidan nasal spray and momethasone furoate nasal spray can inhibit the serological indexes of IL-4,sIgE,GATA3 and the eosinophils secreted in the nose of patients with PAR with Qi deficiency of lung and spleen.It can promote serum IFN-?and T-bet,and regulate Th1/Th2 immune imbalance.