Clinical And Experimental Studies About The Effects Of Gubenfangxiaoyin On The Qi Deficiency Of The Lung And Spleen In The Children With Chronic Bronchial Asthma

Bronchial asthma is the most common chronic respiratory disease in children, as well as a worldwide intractable disease, whose incidence has been increasing with the development of society. Asthma has become a grave public health problem drawing worldwide attention for it not only severely does harm to individual health, but also causes a huge burden to families and society. At present, Western medical treatment of chronic asthma is still lacking of good measures, while Chinese medicine has unique advantages. Traditional Chinese Medicine is an effective therapy on controlling chronic asthma, which can regulate the entire body, support the healthy energy, enhance the power of resistance and reduce the asthma attacks.The prescription Gubenfangxiao decoction (GBFXD) is an empirical prescription from Professor Jiang Yuren, a countrywide famous pediatrician in our department (one of the Nationally 500 Best Old Chinese Medicine Experts.). This formula consisted of honey-fried Radix Astragali, Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Poria, calcined Concha Ostreae, Periostracum Cicadae, Pericarpium Citri Reticulatae, Raidix Saposhnikoviae, Flos Magnoliae, Fructus Schisandrae and raw Radix Glycytthizae. It provided the effects of nourishing lung, secured exterior, invigorated spleen and resolved phlegm, have been used in Jiangsu Province Hospital of TCM for more than 30 years, demonstrating the exact efficacy in clinical application of reducing asthma attacks in frequency and degree, enhancing the children's physical fitness, improving the quality of life and asthma remission rate of the sick children. Currently in the national science & technology pillar program during the eleventh five-year plan period, the project based on such prescription, named as "clinical evaluation of GBFXD curing asthenia of pulmonosplenic qi at childish chronic asthma ", has reached the experimental stage after being declared and approved by the Ministry of Science and Technology. Clinical research part of our work belongs to this project, and the experimental part investigates further mechanism of the prescription as well as its active components preventing and curing asthma using views of both immunology and air tube pathology.Clinical Research ComponentFrom January 2009 to March 2010, following the experimental principle of central randomization and parallel control, we systematically observed the efficacy and safety of TCM curing asthenia of pulmonosplenic qi on childish chronic asthma, at Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Affiliated Oriental Hospital of Beijing University of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, and The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine. Our research does statistical analysis to 100 cases that are treated for more than 6 months, of which 51 cases belong to TCM group,49 cases belong to western drug group.ObjectUsing a central randomized, controlled, multicenter clinical trial, we observed the therapeutic efficacies of both Traditional Chinese Medicine treatment and Western Medicine treatment to objectively evaluate the efficacy and safety of TCM on reducing asthma attack in frequency and degree during the remission stage of childhood asthma.MethodsA multicenter, randomized, controlled method was used to carry out clinical studies on 100 cases of children in asthma remission stage. The trial group administered GBFXD; the control group used Pulmicort Turbuhaler inhaling, both of them were treated for 6 months. Efficacy evaluation of children in both group were carried out after the course of treatment on their primary and secondary clinical disease syndromes. The main indexes as well as symptom scores before and after treatment were compared. SPSS 13.0 software was used for statistical analysis, including chi-square test, t test and Ridit test analysis.Results1. Influence of TCM group on the main indexes of therapeutic efficacy including the number of days without asthmatic symptoms, frequency of asthma attacks, asthma severity, frequency of upper respiratory tract infection, and frequency of lower respiratory tract infection.During the observation period of 6 months treatment, the number of days without asthmatic symptoms, frequency of asthma attacks, and frequency of lower respiratory tract infection of the two groups, had no significant difference by t test. The frequency of upper respiratory tract infection for 6 months TCM group was significantly lower than western medicine group, showing significantly difference by t test, p<0.05. The frequency of upper respiratory tract infection in the 1st,3rd, and 6th month and the frequency of asthma attacks and lower respiratory tract infection in the 3rd, and 6th month of both TCM group and western drug group were significantly lower than baseline, showing significantly difference by t test, p<0.01. Comparing the before and after treatment efficiency of the two groups, TCM group was significantly higher than the western drug group, showing significantly difference by Ridit test, p <0.05. All above-mentioned prompted that TCM group and western drug group both could reduce the frequency of asthma attacks, upper and lower respiratory tract infection, but TCM group showed more significant effect on reducing respiratory infection.After treatment intervention, patients of neither TCM group nor western drug group showed up gradeⅣserious asthma attacks. The severity of asthma attacks of the two groups in 1,3 months have no significant difference; in 6 months show significant difference by Ridit analysis, p<0.01. And the gradeⅡasthma attacks in TCM group were significantly less than in western drug group.Therefore, GBFXD is an effective prescription to cure childhood asthma in remission stage. It has similar efficacy to Pulmicort Turbuhaler in maintaining the number of asymptomatic days and controlling frequency of asthma attacks, while can better alleviate the severe degrees of asthma attack and prevent respiratory tract infection.2. Influence of TCM group on TCM Syndrome of the sick childrenCompared by syndromes efficacy, scores of both group at each time point showed no significant difference except 3 months sweating symptoms,6 months sweating, tongue, food intake and appetite.3 months sweating score of TCM group was significantly lower than western drug group, and 6 months sweating, tongue, food intake and appetite scores were significantly lower than western drug group, with statistical difference by t test, p<0.05, p<0.01. This prompted that TCM group could better improve the children's sweating, loss of appetite and food intake, abnormal symptoms of tongue comparing with western drug group.Nasal itching and sneezing, runny nose, cough, shortness of breath, sweating, tongue, and total symptoms scores of 1 month TCM group were significantly lower than baseline, showing statistical difference (p<0.05, p<0.01); cough, pale, and total symptoms scores of 1 month western drug group were significantly lower than baseline (p<0.05, p<0.01); nasal itching and sneezing, runny nose, cough, shortness of breath, sweating, pale, fatigue, and total symptoms scores of 3 months TCM group were significantly lower than baseline (p<0.05, p<0.01): coughing, shortness of breath, and total symptoms scores of 3 months western drug group were significantly lower than baseline (p<0.05, p<0.01); sneezing, nasal itching, runny nose, cough, shortness of breath, sweating, pale, fatigue, appetite, food intake, stool, tongue, and total symptoms scores of 6 months TCM group were significantly lower than baseline (p<0.01); nasal itching and sneezing, runny nose, cough, shortness of breath, sweating, pale, fatigue, and total symptoms scores of 6 months western drug group were significantly lower than baseline (p<0.05, p<0.01).The above prompt that both TCM group and western drug group can improve clinical symptoms in remission stage of childhood asthma, while TCM group have advantage to improve children sweating, tongue,appetite and food intake.3. Influence of TCM group on the number of combination therapy days for the sick childrenThe number of combination therapy days had no significant difference between the two groups. By observing the number of combination therapy days in 1 month and 3 months, the two groups showed no significant difference; in 6 months and the total period, TCM group was significantly lower than western drug group. This prompted that TCM group can reduce the number of combination therapy days for the sick children.4. Safety Evaluation of TCM group:No abnormal blood, urine, stool for routine, ECG, and liver function, as well as other adverse reactions in patients were observed during the clinical trial period, indicating that GBFXD is clinical safety.ConclusionEfficacy and safety evaluation after 6-month treated on 100 sick children in four research centers suffering from asthenia of pulmonosplenic qi at asthma remission stage.1. Comparing the effects before and after treatment, TCM group could significantly reduce the number of asthma attacks, the frequency of upper and lower respiratory tract infection in sick children, improving clinical symptoms in sick children including:nasal itching and sneezing, runny nose, cough, shortness of breath, sweating, pale, appetite, food intake, stool, and significantly reducing tongue, and the total scores.2.Comparing the effects of TCM group and western drug group, TCM have similar efficacy with Pulmicort Turbuhaler on maintaining the number of asymptomatic days and controlling frequency of asthma attacks, while can better alleviate the severe degrees of asthma attack, prevent respiratory tract infection, and reduce the number of combination therapy days for the sick children. Both TCM group and western drug group can improve clinical symptoms in remission stage of childhood asthma, while TCM group have advantage to improve children sweating, tongue, appetite and food intake.3. Safety Evaluation showed clinical safety of GBFXD.Accordingly, GBFXD is an effective prescription to cure childhood asthma in remission stage with clinical safety. However, a short observation period is still not sure of its long-term outcome after withdrawal. The study at follow-up observation period should be further completed and the sick children's quality of lives should be analyzed to display the advantage of TCM treatment on this disease more objectively, so as to establish the standardized TCM treatment plan in remission stage of Childhood asthma, and to form the propagable treatment guidelines for Childhood asthma treatment in remission stage.Experimental Research Component1. Therapeutic effects of Gubenfangxiao decoction on chronic asthmatic miceAim:To observe the effects of Gubenfangxiao decoction (GBFXD) on chronic asthmatic mice.Methods:BALB/c mice were sensitized with intraperitoneal OVA injection on day 1 and day 11, and with atomization inhaled OVA on day 11, sensitized mice involved with six 2-days periods of atomization inhaled OVA challenges, then the mice were administered intragastrically with GBFXD or distilled water for 4 weeks. The airway hyperresponsiveness, BALF cell counts and cell classifications, IL-4 and IFN-y levels in BALF and lung histological examinations were observed 24 hours after last administration.Results:GBFXD decreased the mice airway hyperresponsiveness, BALF inflammation cell counts and eosinophile granulocyte and neutrophil granulocyte ratios in BALF inflammation cells, meanwhile, GBFXD increased IFN-y levels in BALF and decreased eosinophile granulocyte infiltration in airway.Conclusion:The mechanisms of GBFXD on preventing asthma attack might be ascribed to the decreasing of airway hyperresponsiveness, eosinophile granulocyte infiltration and the increasing of IFN-γlevels. 2. Effects of Astragaloside IV on IFN-gamma level and prolonged airway dysfunction in a murine model of chronic asthmaBackground:Astragaloside IV (AST) was the active constituent of Radix Astragali, a Chinese herb traditionally used to treat asthma. The present study was designed to evaluate the efficacies of AST on chronic asthma, and if so, explored the underlying mechanisms involved.Method:Chronic asthma was induced in mice by sensitization and repeated challenges of ovalbumin (OVA), on which the following outcome measurements were made:(i) in vivo airway responsiveness to intravenous methacholine (MCh, Sigma, St. Louis, Mo.); (ii) total and differential cell counts in bronchoalveolar lavage fluids(BALF); (iii) IL-4 and IFN-gamma levels in BALF supernatants; and (iv) airway morphometry.Results:In this murine model of chronic asthma, the airway dysfunction and remodeling remained severely, accompanying with suppression of IFN-gamma levels in BALF even four weeks after the final challenge. After oral administration of AST for four weeks, the airway responsiveness to intravenous methacholine was sharply reduced, meanwhile the inflammatory cells were decreased but the IFN-gamma levels increased in BALF. The collagen deposition and mucus production were also reduced by AST.Conclusion:AST, a natural constituent from Radix Astragali, was beneficial to chronic asthma, thus it should be served as a supplementary therapy in controlling chronic asthma.