【作者】 詹金淦；

【导师】 汪受传；

【作者基本信息】 南京中医药大学 ， 中医儿科学， 2011， 博士

【摘要】 哮喘是儿童时期最常见的呼吸道慢性疾病之一。近年来世界各国哮喘的发病率均呈现逐渐上升的趋势,发达国家儿童哮喘的患病率高达10%以上。2000年我国儿童哮喘的平均患病率为1.97%,比1990年上升了64.80%。据台湾台北市研究数据显示,儿童哮喘患病率在1974年为1.30%,在1994年则为10.70%,2002年的报告已接近20%,一直呈现上升趋势,值得警惕与担忧。由于哮喘为一种反复发作性疾病,难以根治,所以严重影响患儿的身心健康,也给患儿家长带来了沉重的经济负担和精神压力。台湾哮喘患儿众多,患者多求助中医。据临床观察,由于台湾地理气候特点及患儿体质特点,小儿哮喘以热哮证居多。定喘汤是古代治疗热哮证的名方,是否可用于台湾哮喘患儿,疗效如何?本文就此做临床观察研究,并作出客观评估。目的本研究在温习古今文献及既往临床经验的基础上,针对小儿热哮证设计临床试验,同时应用临床试验前的数据分析以建立台湾小儿哮喘的流行病学资料。客观评价清肺涤痰平喘法治疗小儿热哮证的临床疗效；比较中医、西医、中西医结合三种治疗方案在小儿热哮证治疗中的有效性与安全性。进一步探讨疾病疗效评价方法,以为建立新的、更为客观的,且能显示中医药治疗本病优势和特色的疗效评价方法建立基础。方法采用区组随机、对照、部分双盲的临床研究方法,对120例确诊为热哮证的患儿,分为3组,A组(西药基础治疗加定喘汤组)30例、B组(西药基础治疗加安慰剂组)30例、C组(定喘汤组)60例,7天为1个疗程,随访不少于12周。主要的评估指标为主症积分、次症积分、热哮证证候严重程度改善情况、整体症状改善情况、西药用量、肺功能(FEV1、FVC)、呼吸道敏感度和血中IgE、组织胺及LTC4浓度变化等。同时分析上述量化指标与热哮证的相关性。比较3组的临床疗效以及其安全性。采用SPSS13.0软件对结果进行统计分析,包括t检验、卡方检验等分析。结果本组共观察120例患儿,均完成全部疗程,绝大多数患儿在治疗1周内见效。主症积分变化、次症积分变化、热哮证证候严重程度改善情况,3组治疗前后均有显著差异(p<0.05),治疗后优于治疗前,组间比较则A组疗效明显优于B组、C组。A组methacholine激发测试(0.51±1.05mg/ml vs.0.26±0.84mg/ml p=0.034),整体症状改善及药物减量(p=0.004),治疗后明显改善；B组、C组则未见类似变化。主症的咳嗽、咯痰痰鸣,次症的二便,热哮证证候严重程度改善,C组较B组为佳(p<0.05)。另外,虽然3组均无法显著降低血中IgE,但IgE高的患儿治疗反应比较好。此外,我们利用进入临床试验前的数据,进一步分析发现台湾小儿热哮证约占70%,热哮证患儿肺功能显著低于非热哮证患儿(FEV1,p=0.030)；热哮证越明显,肺功能越差(FEV1vs呼吸道指标,p=0.034)；经中西医结合治疗后,热哮证明显改善(p<0.00001)；肺功能亦有改善但无统计学差异；证候指标中,黄痰组FVC改善程度显著优于非黄痰组(p=0.026)。结论在台湾小儿哮喘中,热哮证约占70%。热哮证患儿肺功能显著低于非热哮证者；热哮证越明显,肺功能越差；经中西医结合治疗后,热哮证明显改善；单纯中药组比单纯西药组改善热哮证若干证候的效果较好。定喘汤、西药均可有效治疗小儿热哮证,但西药加定喘汤组的中西医结合治疗疗效更佳。更多还原

【Abstract】 Asthma is the most popular chronic disease in children and no radical treatment till now. In recently, the prevalence of children asthma is increasing, and it is even getting higer up to 10% in developing country. The prevalence of asthma in children was 1.97% in 2000, compared with an increase of 64.80% in 1990. According to research data of Taibei, Taiwan, it shows that prevalence was 1.30% in 1974, compared to 10.70% in 1994 and nearly 20% in 2002. It has shown an upward trend, and worthy of attention and concern. Because of a chronic, recurrent disease and difficult to cure disease, so asthma not only seriously affects children health, but also brought a heavy financial burden and mental stress to children parents. Traditional Chinese medicine (TCM) has a long history of application for patients in clinics. Because of the characteristics of Taiwan’s geography and climate and physical characteristics of children, most of children asthma is the heat pattern. Ding Chuan Tang (DCT) is one of the formulas especially in treatment of heat pattern asthma. Is it necessarily that TCM should be based on diagnostic pattern identification? How about is the efficacy? Both problems are we concerned.ObjectiveWe foccused on children asthma of heat pattern for clinical trials in this study and also used the run-in period data analysis to establish the epidemiological data of asthma in children in Taiwan. We evaluate clinical effect of TCM methods objectively and to evaluate the safety of TCM methods on children’s asthma of heat pattern syndrome. We further discuss the method of effect evaluation and establish a new effect evaluation method on children’s asthma of heat pattern syndrome.MethodsWe design a randomized, parallel-group, multicenter clinical trial of 120 patients diagnosed as hot pattern children with asthma, divided into 3 groups, A group (Western medicine therapy plus DCT therapy group) 30 cases, B group (Western medicine therapy plus placebo group) 30 cases, C group (DCT therapy group) 60 cases.7 days for a course of treatment and follow-up is not less than 12 weeks.Chinese symptoms and signs, heat pattern severity score, self recorded daily symptom scores, medication scores, and morning and evening peak expiratory flow rates were returned during first week and the monthly clinic. Pulmonary function test, methacholine challenge test, and serum inflammatory mediators were measured before and at the end of the trial. The relationship between the above objective parameters and heat severity and patterns will be analyzed by statistics.Results Total 120 asthmatic children (A group 30; B group 30; C group 60) completed the clinical study. All the three groups patients achieve significant improvement on objective efficacy of major symptoms, major symptom scores, minor symptom scores, heat pattern severity (p<0.05). The combined treatment group is significantly better than the other two groups. At the end of the treatment period, airway hyper-responsiveness determined by logPC20 was significantly improved in the DCT group (0.51±1.05 mg/ml vs.0.26±0.84 mg/ml, p=0.034), however, no significant change was found in the other two group. Besides, the total clinical and medication reduced parameters showed improvement in the A group (p=0.004). About the main symptoms of cough, sputum expectoration, symptoms of stool and urine, and the heat asthma severity improvement, C group is better than the B group (p<0.05). In addition, although the three groups were not significantly lower blood IgE, but children with high IgE response to treatment is better.In addition, we use the data before enrolled the clinical trial, and further analysis showed that heat pattern children asthma is about 70% in Taiwan. The poor pulmonary function was seen in patients of heat-pattern group than non-heat-pattern group (FEV1, p=0.030). The more heat severity was seen, the more poor pulmonary lung function was noted (FEV1 vs SC,p=0.034). After treatment, the heat severity got significant improvement (p<0.00001), and pulmonary function got improvement, too. Within all of the diagnostic parameters, yellowish phlegm is highly associated with pulmonary function (FVC, p=0.119), and the change of FVC shows significant difference (-5.97±1.87 vs.5.22±6.03% predicted, p=0.026).ConclusionIn Taiwan Heat Pattern Children asthma is about 70%.The poor pulmonary function was seen in patients of heat-pattern group. The more heat severity was seen, the poor pulmonary lung function was noted. After treatment, the heat severity got significant improvement on all three groups. Chinese medicine only group got better improvement than western medicine only group in the heat physical effects. Both DCT and fluticasone may treat asthma, however, combined treatment group got better efficacy.更多还原