Clinical Study On The Clinical And Mechanism Of "Qufeng Huoxue, Huatanzhike" In Treating Children With Cough Variant Asthma

This research mainly includes 4 parts:literature review, clinical research, experimental research, mechanism study. Sum up current overview about cough variant asthma of Chinese and Western medicine. Analyze pathogenesis regularity of lung wind syndrome. Observe the clinical curative effect evaluation of my tutor. Sum up the understanding and treatment experience of my tutor. Explore the mechanism of "expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough" method in the treatment of cough variant asthma.1 Literature reviewRetrieve relevant documents about the cough variant asthma; Analyze its incidence, disease; Summarize the evolution of TCM disease name, etiology and pathogenesis and current status of TCM treatment; Summarize related causes, pathogenesis, diagnosis, differential diagnosis and treatment status of Western medicine.2 Clinical study of "expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough" method in treatment of lung wind syndrome cough variant asthma childrenObject(1)To observe the pathogenesis of cough variant asthma lung wind syndrome. To innovate and perfect the theory of "expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough". To provide an new theoretical basis for the treatment of traditional Chinese medicine.(2)To discuss pathogenesis regularity of cough variant asthma lung wind syndrome.(3)To observe the effectiveness and security of added Xiongxie Powder.(4)To provide new theory, treatment method and effective drugs for the prevention of the occurrence, development and treatment of cough variant asthma,Method(1)We designed the registration form of cases firstly. The samples were from the same statistical population in order to follow the balance of statistic principle. The cases conforming to the eligibility were selected. We established a database with gender, age, course of this time treatment, general course of disease, disease happening and contributing factors, past medical history, allergic diseases, family history of allergic, personal history, complications, and frequency or structure of ratio analysis of results.(2)We employed own contrast experiment design, and the 36 patients meeting the inclusion criteria of cough variant asthma lung wind syndrome were treated by Added Xiongxie Powder for 28 days which was one period of treatment. Evaluation point:one time before and after treatment each. Evaluation content:single, primary, minor symptom score; total score; cases number of individual symptom, a single symptom and syndrome total effective rates.Result(1)There were more males children than females, men and women ratio was 2.1:1. Preschool and school-age children had high incidence. Respiratory tract infection, movement factor, contact special smells were the most common factors of disease causing or increasing. Allergic rhinitis and eczema were most common allergic disease, More than half children had family history of allergic disease, and allergic rhinitis family history was the most common. Majority children liked eating sweet foods. Allergic rhinitis is the most common complications of the children with cough variant asthma.(2)Main symptoms score, secondary symptoms score, total symptoms score were lower than those before treatment. After treatment the total effective rate was 87.10%. The score and the number of cases were reduced in the symptoms of cough frequency, cough degree, cough nature, phlegm, short of breath, chest tightness, pharyngeal itching, abnormal defecate, an abnormal sleep symptoms. Abnormal sweating symptoms score decreased, but reduce about the number of cases had no statistical significance. The score and the number of diet abnormal symptom was less, but reduce had no statistical significance.ConclusionThe clinical curative effect method of " expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough" in treatment of children with cough variant asthma is sure. The improve is remarkable in the symptoms of cough frequency, cough degree, cough nature, phlegm, short of breath, chest tightness, pharyngeal itching, abnormal defecate, an abnormal sleep symptoms.3 The related clinical experience of Professor XU Rong-qian in the treatment of cough variant asthma(1)In the treatment course of cough variant asthma, expelling the wind and promoting blood circulation should be throughout the course of total treatment. Eliminating phlegm should abide by syndrome differentiation, and we should be good at regulating lung qi activity so as to achieve relieve cough. In remission, according to different constitution and virtual zang-fu organs, the children still need to insist on treatment and appropriate tonic. In order to cut off the pathway of evil qi entrance, paying attention to regulate nose pharynx ministry is also significant which can play a role of positive prevention and make the portal of the lung.(2)Combining many years of clinical experience, my tutor professor Xu Rong-qian consider that the incidence of pathological factors of cough variant asthma are wind, phlegm and blood stasis. He thinks that this disease exist external-wind invocating internal-wind, stubborn sputum in lung, and blood stasis due to chronic illness. The main pathological mechanism of this disease is the stagnation of wind, phlegm and blood stasis. The basic principle of treatment is expelling wind, activating blood flow, preventing phlegm forming and stopping coughing. Basing on the ancient famous recipe of xiongxie powder, the new recipe which called powder of added xiongxie adds Baiqian, Danggui, Taoren. We use this recipe as basis recipe, thus plus or minus herbs according different syndromes.(3)In terms of acupoint sticking therapy, teacher pay attention to regulate lung qi activity, The basis recipe is Huaxiang stopping cough powder sticking to CV 8 point, thus plus or minus herbs according different syndromes.4 Mechanism study of " expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough" method in the treatment of cough variant asthma ObjectTo explore the mechanism of "expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough" method in the treatment of cough variant asthma. Clearly putting forward the characteristics of multiple ways, multiple targets, multiple links about the therapy.Method4 months aged Wistar rats were randomly divided into the control group, the model group, the singulair group (1.2 mg·-kg-1·d-1), and the Added Xiongxie Powder high (8.64 mg·kg-1), medium (4.32 mg·kg-1), low (2.16 mg·kg-1) dose groups. Except control group, the cough variant asthma model groups were intramusculared 4% OVA solution 0.5 ml from the first day, and injected 2%AL(OH)3 0.2 ml in intraperitoneal, one time each day. From the fourteenth day, the cough variant asthma model groups were inhaled 1% OVA solution for 2 minutes, one time each two days for 7 times. All rats were gavaged continuously for 15 days from the fourteenth day. After detecting cough frequency, we observed pulmonary pathology by HE staining, observed inflammatory cells in BALF by Wright’s staining, observed the extracellular matrix deposition by Masson staining, observed the protein expression of TGF-β1、p38、p-p38、JAK2、STAT3、p-STAT3 by immunohistochemistry, observed the mRNA expressions of MMP-9、TIMP-1、TGF-β1、JAK2、STAT3 in rats’lung tissue by real time fluorescent quantitative PCR.Result(1)HE staining:There was obvious inflammatory change in lung tissue of rats in the model group, and the pathological change of treatment groups was improving.(2)Wright’s staining:There were obvious infiltration of inflammatory cells in the bronchoalveolar lavage fluid in the model group, and the inflammatory cells of treatment groups were decreasing.(3)Masson staining:There was obvious extracellular matrix deposition in lung tissue of rats in the model group, and the pathological changes of treatment groups was alleviating.(4)The cough frequency in the model group was enhancing (P<0.01), compared with model group, the cough frequent of high and medium dose Added Xiongxie Powder groups was reducing (P<0.01), the cough frequent of low dose Added Xiongxie Powder group was reducing (P<0.05).(5)Immunohistochemistry:The protein expression of TGF-β1,p38, p-p38, JAK2,STAT3, p-STAT3 in the model group was enhancing (P<0.01). Compared with model group, each dosage Added Xiongxie Powder could reduce protein expression of TGF-β1, p38, p-p38, JAK2, STAT3 (P<0.01). Compared with model group, the high and medium dose Added Xiongxie Powder could reduce the protein expression of p-STAT3 (P<0.01), the low dose Added Xiongxie Powder could reduce the protein expression of p-STAT3 (P<0.05)(6)Real time fluorescent quantitative PCR:The mRNA expression of TGF-β1, p38, p-p38, JAK2, STAT3, p-STAT3 in the model group was enhancing (P<0.01); Compared with model group, the high and medium dose Added Xiongxie Powder could reduce the expression of MMP-9, TIMP-1, JAK2 mRNA in lung tissue (P<0.01), the low dose Added Xiongxie Powder could reduce the expression of MMP-9, TIMP-1, JAK2 mRNA in lung tissue (P< 0.05). Compared with model group, each dosage Added Xiongxie Powder could reduce expression of TGF-β1, STAT3 mRNA (P<0.01)Conclusion(1)Cough variant asthma can lead to extracellular matrix in the lung tissues of rats, increase of MMP-9, TIMP-1 is involved in extracellular matrix deposition; Cough variant asthma can lead to lung tissue of model rats with fibrosis, increase of TGF-β1, p38, p-p38 is involved in pulmonary fibrosis; Cough variant asthma can lead to airway inflammatory responses in the lung tissues of rats, increase of JAK2, STAT3, p-STAT3 is involved in airway inflammation.(2)The western medicine group and each dose Added Xiongxie Powder can improve the extracellular matrix deposition in lung tissue, pulmonary fibrosis, airway inflammation, in which traditional Chinese medicine high dose group has the best effect, and the low dose of has the poor effect.(3)The improve of the extracellular matrix deposition may be related to down-regulation of MMP-9, TIMP-1 expression in lung tissue; The improve of the pulmonary fibrosis may be related to down-regulation of TGF-β1, p38, p-p38 expression in lung tissue; The improvement of the airway inflammation may be related to down-regulation of JAK2, STAT3, p-STAT3 expression in lung tissue.(4)The main pathological factors of cough variant asthma are wind, phlegm, blood stasis; The main pathological mechanism of this disease is the stagnation of wind, phlegm and blood stasis. The main therapeutic principle is "expelling the wind and promoting blood circulation, eliminating phlegm and stopping cough"; Using Chinese medicine treatment method by Added Xiongxie Powder has an extremely important role.