| BackgroundIn recent years,with the rising trend of the incidence of post-infection cough(PIC),its pathogenesis is still not very clear so far,so the current treatment of Western medicine is lack of effective drugs.It has become a big problem in social life for people living in the city in the fast-paced work.Without timely and effective treatment,PIC can develop into chronic diseases or other complications,which will cause a heavy economy burden and decline the quality of patients' s life.In the clinical research based on the basis of early clini'cal study,we summarized the characteristics of the patients with symptoms of cough after infection and found that due to climate warming,the fast rhythm of life,irrational diet and other unreasonable factors,affecting the normal operation of qi,qi ascending and descending dysfunction,qi stagnation,stagnant heat,make the modern people form"stagnant heat pathogen"in physical fitness.If exogenous evil invades the lung and pulmonary qi impairment,which can not resist the evil for a long time,leading to the exogenous evil linger and difficult to heal,developing into post-infectious cough.Applying the Fu-Xie theory,we can explore the etiology and pathogenesis characteristics of the post-infectious cough(stagnant heat incubated in the body,exogenous evil not be expelled),which can guide the clinical differentiation and treatment.Then we can further recognize theses diseases and improve the clinical curative effect.The main treatment of PIC stresses dissipating and expelling evil,relieving stagnation to clear heat,regulating qi ascending and descending.Professor gao often uses modified Bainiuxuanfei decoction treatment of post-infectious cough.Therefore it is particularly important for clinicians to correctly understand cough post infectious,disseminate the standardization of diagnosis and treatment,improve the curative effect,shorten the length of the disease and improve the quality of life for patients.ObjectiveThe research is to study the etiology and pathogenesis of PIC based on the Fu-Xie theory.The syndromes of stagnant heat incubated in the body and exogenous evil not be expelled is the key pathogenesis of cough post infectious,with the principle of dissipating and expelling evil,relieving stagnation to clear heat,regulating qi ascending and descending,using modified Bainiuxuanfei decoction treatment of post-infectious cough.Through clinical experiment,we observe clinical curative effects and safety of modified Bainiuxuanfei decoction on PIC;through animal experimental,we study the action mechanism of modified Bainiuxuanfei decoction in treating cough after infection.MethodsClinical research:The study was prospective,randomized,double-blind,double simulation,controlled clinical trial.All cases were patients admitted from December 2015 to January 2017 in Guang'anmen Hospital of Chinese Academy of traditional Chinese medicine outpatients in emergency and cough clinics.Totally 70 cases of postinfectious cough with stagnant heat incubated in the body and exogenous evil invading the lung pattern were randomly divided into the treatment group and the control group.The treatment group were treated with Bainiuxuanfei Decoction and Montelukast sodium tablets simulants;the control group were treated with Bainiuxuanfei Decoction simulants and Montelukast sodium tablets.The treatment and follow-up lasted for seven days.Comparing the baseline indicators:demographic data and clinical data.The main evaluation indicator included the daytime and nighttime cough symptom scores,the Visual analogue scale of cough symptoms score,curative effect of cough time,cough recurrence.Secondary outcomes measures included the changes of the integrated symptom and single symptom,the Leicester cough questionnaire and safety indicators(such as blood routine,liver and kidney function,and adverse reactions),economic indicators(the days of delay work and the average cost of illness).Experimental study:Based on a randomized control study using cough after infection animal model,the SD rats are divided into normal control group,PIC model group,modified Bainiuxuanfei decoction of low,middle and high dose group and western medicine group(Montelukast sodium).By capsaicin stimulation test,observing the behavior changes of rats and cough properties,the frequency of cough and the cough latent time.Observing the pathological changes of lung tissue by HE staining;ELISA method is used to detect BALF content of cytokine(IL-4,IL-5,IL-8,TNF-alpha),bradykinin(SP,NKA)and calcitonin gene related peptide(CGRP);exploring the effect of intervention on cough after infection of airway inflammation and airway neurogenic inflammation of modified Bainiuxuanfei decoction.Results1 Clinical studyThe clinical trials of patients are observed in 70 cases,2 cases are excluded,3 cases are falling off.There are 33 cases in treatment group,32 cases in the control group.In the demographic data,TCM syndrome score,symptom score,cough symptom score,treatment group and control group before the treatment are no statistically significant difference(P>0.05),two groups of data of baseline is balanced and comparable.1.1 Antitussive effectIn modified Bainiuxuanfei decoction group,the daytime cough symptom score is(0.30±0.52),it was significantly lower than that of control group which is(0.81±0.99)(P<0.05).The total effective rate of daytime cough in Chinese medicine group is 90.91%and 62.50%in the control group,two groups were compared,P<0.05;in modified Bainiuxuanfei decoction group,the nighttime cough symptom score is(0.48±1.60),the control group was(0.56±1.07).The total effective rate of nighttime cough in the traditional Chinese medicine group is 87.87%,56.25%in the control group,Chinese medicine group night cough symptom score is improved significantly compared with the control group(P<0.05).In the Visual analogue scale of cough symptoms score:modified Bainiuxuanfei decoction group after treatment score is(0.54±1.00),the control group is(1.31±1.71),the result show that the Chinese medicine group is superior to the control group with statistical significance(P<0.05).Curative effect of cough time:In the modified Bainiuxuanfei decoction group,the onset time of cough is(2.84±0.66)days,the relieve time of cough is(3.66±1.21)days and the disappearance time of cough is(6.15 ±1.69)days;In the control group,the onset time of cough is(5.09±2.56)days,the relieve time of cough is(6.06±3.44)days,the disappearance time of cough is(8.31 ± 3.85)days,the results show that modified Bainiuxuanfei decoction formula is superior to the control groups in shortening the period of treatment,with statistical significance(P<0.001,P<0.01,P<0.01).Cough recurrence:In the modified Bainiuxuanfei decoction group,the recurrence rate of the cough is 12.50%,the control group is 40.00%,comparing between two groups,P<0.05,the results showed that the recurrence rate of the Chinese medicine group was significantly lower than that in the control group.In the modified Bainiuxuanfei decoction group,the recurrence frequency of cough are(0.15±0.36),the recurrence time of cough are(0.36±0.92)days;in the control group,the recurrence frequency of cough are(0.78±1.12),the recurrence time of cough are(1.00±1.36)days.The results show that modified Bainiuxuanfei decoction formula is superior to the control groups in reducing the recurrence rate of PIC,with statistical significance(P<0.01,P<0.05).Evaluation of life quality:In the aspect of cough influence on the quality of life,in modified Bainiuxuanfei decoction group,Leicester Cough Questionnaire(LCQ)score after treatment is(16.08±2.03),Leicester Cough Questionnaire(LCQ)score of physiologica is(5.33±0.55),LCQ Society score after treatment is(5.27±1.11),LCQ psychological score is(5.18±0.47);in the control group,LCQ score after treatment is(14.98±1.60),LCQ score of physiologica is(4.85 ± 0.71),LCQ Society score after treatment is(4.63±0.89),LCQ psychological scores is(4.81±0.58),the results show that modified Bainiuxuanfei formula is superior to the control group in improving quality of life of patients with cough post infectious,with statistical significance(P<0.01,P<0.01,P<0.01,P<0.05).1.2 Comprehensive analysis of symptoms curative effect:In the aspect of comprehensive analysis of symptoms curative effect,in modified Bainiuxuanfei decoction group TCM syndrome total score after treatment is(1.66±1.38);in the control group,TCM syndrome total score after treatment is(3.68±3.14),the result shows that modified Bainiuxuanfei formula is superior to the control groups in improving the symptoms of cough post infectious,with statistical significance(P<0.01).The results indicate that the Chinese medicine group could obviously improve symptoms of cough post infectious,such as the itching throat,sore throat,sputum,urine score,compared with the control group P<0.05.1.3 Safety and economic evaluationThe research results indicates that modified Bainiuxuanfei decoction with high safety have no toxic and side effects.In the clinical study,no adverse events occurred which shows that the study drugs have no side effect within the normal dose.The average cost of Chinese medicine group is(335.21±202.14)yuan,the average cost of the control group is(745.40±474.68)yuan,compared with the cost between the two groups,P<0.05,the results show that the days of delay work in modified Bainiuxuanfei decoction is lower than that of the control group,with statistical significance(P<0.05).2 Experimental study2.1 The cough frequency and cough latency2.1.1 Comparison of cough provocation test of using drugs in the first day In six groups,the order of cough frequency in 10min from low to high is normal control group,high dosage group and Western medicine control group,model group,Chinese medicine middle dosage group,low dosage of Chinese medicine group.Compared with normal control group,the number of cough frequency is significantly increasing in the model group(P<0.001).High dosage of Chinese Medicine group and model group significantly reduce cough frequency(P<0.05).The order of cough latency from low to high is the model group,low dosage group,normal dose group,western medicine group,middle dose of Chinese medicine group,Chinese medicine high dose group.Compared with normal control group,the model group significantly reduce the cough incubation period(P<0.001).Every dose of Chinese medicine group,western medicine group can significantly prolong the cough incubation period in rats,with statistical significance(P<0.05,P<0.01,P<0.001,P<0.01).2.1.2 Comparison of cough provocation test of using drugs in the seventh day In six groups,the order of cough frequency in 10min from low to high is the normal control group,western medicine group,high dose group and low dose group,middle dose of Chinese medicine group,model group.Compared with normal control group,the model group significantly increase the number of cough frequency(P<0.001),the cough incubation period in normal controlgroup is the most,the second order from more to less is middle dose group,high-dose group,western medicine group,low dose of Chinese medicine group,the model group.Compared with normal control group the model group significantly reduced the incubation period of cough(P<0.001).High and middle dose of Chinese medicine group,western medicine group can significantly prolong the cough incubation period in rats,with statistical significance(P<0.05,P<0.05,P<0.01)?2.2 Detecting the content of BALF cytokines BALF TNF-a concentration of rats in middle dose and high dose of Chinese medicine group and Western medicine group are lower than in the model group(P<0.001,P<0.01,P<0.001).BALF IL-8 concentration of rats in middle dose and high dose of Chinese medicine group are lower than in the model group(P<0.05),the western medicine group compared with model group,no significant difference(P>0.05).BALF IL-4 concentration of rats in middle dose and high dose of Chinese medicine group and Western medicine group are lower than in the model group(P<0.001,P<0.001,P<0.001).BALF IL-5 concentration of rats in low,middle dose and high dose of Chinese medicine group and Western medicine group are lower than in the model group(P<0.05,P<0.05,P<0.01,P<0.01).Compared with western medicine group,high dose in Chinese medicine group is decreased more significantly(P<0.05).2.3 Detecting the content of BALF supernatant medium kinin SP,NKA and CGRPThe content of BALF NKA in middle and high dose in traditional Chinese medicine group and Western medicine group are lower than model group,with statistical significance(P<0.05,P<0.01.P<0.01,P<0.01).The speed of BALF SP in low,middle and high dose of traditional Chinese medicine group and Western medicine group are lower than model group,with statistical significance(P<0.05,P<0.01.P<0.001,P<0.01).Compared with western medicine group,high dose in Chinese medicine group is decreased more significantly(P<0.05).Every dose of traditional Chinese medicine group and Western medicine group can inhibit the release of calcitonin gene related peptide(CGRP)in rats,with statistical significance(P<0.001,P<0.001,P<0.001,P<0.001)?2.4 Lung tissue histopathologyUnder light microscopy,there are different degrees pathological changes in bronchial mucosa,submucosa laye,the condition of inflammatory cell infiltration in bronchostenosis,the alveolar cavity and the surrounding,thickening of bronchial mucosa duplicature,desquamalion of epithelial cells,etc.All dose in Chinese medicine group and Western medicine control group can relieve the pathological changes in rats.Conclusion1 Clinical researchExogenous evil invading the lung and stagant heat incubating in the body syndrome of cough post infectious is very common in clinic,which is more likely to occur in femals and young patients.The etiology and pathogenesis characteristics of the post-infectious cough is stagnant heat incubated in the body,exogenous evil not be expelled,and pulmonary Qi impairment.Modified Bainiuxuanfei decoction could dissipate expell evil,relieve stagnation to clear heat,regulate qi ascending and descending.Modified Bainiuxuanfei decoction has significant clinical curative effects on cough post infectious,such as decreasing the daytime and nighttime cough symptom scores and the Visual analogue scale of cough symptoms score,shortening the time of cough,reducing the cough recurrence rate,improving cough symptoms,shorttening period of treatment and improving the quality of life for patients.It can also obviously improve symptoms of cough post infectious,such as the itching throat,sore throat,sputum,urine score.It has the advantage of safe,economical benefits and no recurrence.2 Experimental studyBy using the animal model of PIC,the modified Bainiuxuafei decoction can reduce the number of cough frequency,and prolong the times of cough latency.In this experimentl study,the results show that modified Bainiuxuanfei decoction can alleviate the airway inflammation by inhibiting the release of cytokines(TNF-a,IL-8,IL-4 and IL-5),and can also significantly inhibit airway neurogenic inflammation by reducing the concentration of NKA,SP and CGRP,and then decreasing cough reflex sensitivity,relieving the airway hyperresponsiveness,and thus effectively in treating post infectious cough. |
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