【作者】 廖若莎；

【导师】 李宜瑞；

【作者基本信息】 广州中医药大学 ， 中医儿科学， 2009， 博士

【摘要】 目的文献研究:系统评价儿童反复呼吸道感染(Recurrent respiratory tractinfection RRTI)中医药治疗性文献,评估研究质量的总体水平,评价中医药疗法的有效性和安全性。发现中医药研究存在问题,确定本课题主要研究思路及方法。临床研究:确定广州地区RRTI患儿非急性感染期中医证型分类及其证候基本特征;阐明中医证型与病情、中医四诊、西医症状体征、免疫指标之间的关系,提高临床辨证水平,为拟定证候诊断标准以及制订治疗方案提供依据,为研究本病提供科学的思路与方法。方法文献研究:以儿童RRTI中医药治疗性文献为评价对象,根据流行病学/DME方法学的原则与方法制定《中医药治疗儿童RRTI文献系统评价及信息采集表》,对中医药治疗RRTI的随机对照研究进行质量评价,分析科研设计、实施以及疗效评价等方面的现状及存在的问题,并把中西药疗法对照的文献进行Meta分析。临床研究:本研究选择广州地区417例反复呼吸道感染非急性感染期患儿为研究对象,通过流行病学的研究方法,采用调查问卷,前瞻性追踪收集患儿一般信息,中医四诊,西医临床症状体征,以及部分患儿免疫球蛋白,补体和T细胞亚群等资料,录入数据建成数据库。对所有指标进行频数统计、聚类分析,分析归纳中医证候分布特点,确定其基本证候类型及其证候特征。针对不同样本类型,用Kruskal-WallisTest、Cochran-Mantel-Haenszel检验、方差分析和卡方检验等统计分析方法分析证型与病情分级、中医四诊、西医症状体征以及免疫指标之间的关系。结果文献研究:1.共检出随机对照试验(RCT)文献141篇,进行Jadad质量记分,1篇为3分,27篇为2分,其余113篇文献均为1分。文献质量低下表现为:(1)缺乏明确纳入标准,排除标准,尤其是中医证候诊断标准,缺乏公认的疗效判定标准。(2)不重视中医药疗法的标准化,稳定性以及不良反应监测。(3)方法学水平有待提高,如:正确运用随机化原则,盲法,统计学方法。2.Meta分析结果显示,无论是中药组,中成药组,中药加载西药组,中成药加载西药组与西药组的优势比均位于95%可信区间内,说明以上的中医药治疗措施对疗效的影响具有统计学意义。临床研究:1.广州地区儿童反复呼吸道感染非急性感染期证候类型以及基本特征:(1)肺气虚弱,卫阳不固证,共103例,占24.7%。主要证候为咳声低弱,喘促气短,恶风,畏寒肢冷,自汗,肠鸣,口干,面白无华,舌淡白,弱脉。(2)肺脾气虚夹滞证,共145例,占34.8%。主要证候为久咳不愈,恶风,乏力,食少,纳呆,腹胀闷,腹痛,大便干结,排便困难,夜眠不安,横形山根,口干欲饮,白苔,厚苔,滑脉,细脉。(3)脾虚肝旺证,共87例,占20.9%。主要证候为面色萎黄,纳呆,山根色青,夜眠不安,易发脾气,口干欲饮,五心烦热,唇淡白,舌红,脉弦。(4)肺肾气虚夹痰证,共82例,占19.7%。主要证候为久咳不愈,咳声低弱,痰声重浊,喘促气短,自汗,面色无华,食少纳呆,眼眶黧黑,毛发无光泽,夜尿遗尿,夜眠不安,滑脉,弱脉。2.各种证候类型的临床资料比较(1)各证型年龄分段,总病程,发病次数,发病病种,发病病程,免疫球蛋白,补体,T细胞亚群以及久咳不愈,咯痰,喘促气短,乏力,面色改变的比较,差异无统计学意义(P＞0.05)。(2)各证型咳声低弱的比较,差异有统计学意义(P＜0.05)。其中脾虚肝旺证与肺气虚弱,卫阳不固证、肺肾气虚夹痰证差异有统计学意义(P＜0.01)。其余组间比较差异无统计学意义(P＞0.05)。(3)各证型恶风,出汗情况的比较,差异有统计学意义(P＜0.05)。肺气虚弱,卫阳不固证与脾虚肝旺证、肺肾气虚夹痰证,肺脾气虚夹滞证与脾虚肝旺证差异均有统计学意义(P＜0.05)。(4)各证型山根色泽、形状情况的比较,差异有统计学意义(P＜0.05)。肺气虚弱,卫阳不固证与肺脾气虚夹滞证、脾虚肝旺证,肺肾气虚夹痰证与肺脾气虚夹滞证、脾虚肝旺证差异均有统计学意义(P＜0.05)。(5)各证型眼眶黧黑、夜尿遗尿、畏寒肢冷比较,肺肾气虚夹痰证与其他三证差异有统计学意义(P＜0.05)。毛发情况比较,肺脾气虚夹滞证与脾虚肝旺证差异无统计学意义(P＞0.05)。其余各组间差异有统计学意义(P＜0.05)。(6)各证型形体消瘦、食少纳呆、腹胀腹痛、肠鸣比较,肺气虚弱,卫阳不固证与其他三证差异均有统计学意义(P＜0.05)。恶心呕吐比较,肺肾气虚夹痰证与肺脾气虚夹滞证、脾虚肝旺证差异有统计学意义(P＜0.05)。大便干结比较肺气虚弱,卫阳不固证与肺肾气虚夹痰证、肺脾气虚夹滞证与脾虚肝旺证差异无统计学意义(P＞0.05)。其余各组间差异有统计学意义(P＜0.05)。(7)各证型五心烦热、口干咽噪、夜眠不安比较,脾虚肝旺证与其他三证差异有统计学意义(P＜0.05)。肺肾气虚夹痰证与肺气虚弱,卫阳不固证、肺脾气虚夹滞证差异均无统计学意义(P＞0.05)。(8)舌色比较,肺气虚弱,卫阳不固证与其余三证、脾虚肝旺证与肺肾气虚夹痰证差异有统计学意义(P＜0.05)。舌苔比较,肺气虚弱,卫阳不固证与脾虚肝旺证、肺肾气虚夹痰证差异有统计学意义(P＜0.05)。脉象比较,肺气虚弱,卫阳不固证与脾虚肝旺证、肺肾气虚夹痰证,肺脾气虚夹滞证与脾虚肝旺证、肺肾气虚夹痰证差异均有统计学意义(P＜0.05)。结论文献研究:1.Meta分析显示中医药治疗儿童RRTI有一定疗效,但不排除治疗组与对照组疗效差异与实验方法学质量低下有关。2.文献质量分析显示目前中医药治疗儿童RRTI的随机对照研究质量有待提高,现有结论缺乏足够说服力。临床部分:1.广州地区儿童反复呼吸道感染非急性感染期证候类型分为四种:肺气虚弱,卫阳不固证、肺脾气虚夹滞证、脾虚肝旺证和肺肾气虚夹痰证。主要证型是肺脾气虚夹滞证。2.年龄分段,总病程,病情分级,免疫指标,久咳不愈,咯痰,喘促气短以及乏力对于中医辨证价值不大。3.虽然面色改变各证型比较差异无统计学意义,但其辨证意义应在今后研究中进一步论证。4.咳声低弱,恶风,出汗情况与肺气虚弱,卫阳不固证和肺脾气虚夹滞证关系密切。山根望诊,形瘦纳呆,腹胀腹痛,恶心呕吐等则是肺脾气虚夹滞证与脾虚肝旺证主要辨证指标。五心烦热,口干咽噪,夜眠不安对于脾虚肝旺证辨证价值较大;眼眶黧黑,毛发色黄干枯,夜尿遗尿,畏寒肢冷在肺肾气虚夹痰证辨证占重要地位。舌象、脉象综合反映疾病的病因、性质、部位、轻重以及转化,其辨证作用无可替代。更多还原

【Abstract】 ObjectiveDocumentary research:to review systematically the TCM remedial documents of recurrent respiratory tract infection(RRTI);to evaluate the overall quality of relative researches and the efficacy and safety of TCM therapy; and to determine the research methods for this subject.Clinical research:to identify the types and characteristics of RRTI sick children in non-acute inflammation stage in Guangzhou;to illustrate the relations among Traditional Chinese Medicine(TCM) types and symptoms,the four physical examinations in TCM,symptoms in Western Medicine,and immunity index,which may provide some guidelines for the standardization of the differentiation and treatment,and scientific thinking and ways for the research of this disease.MethodsDocumentary research:firstly,to establish the "the Evaluation and Information Collection Form on TCM Therapy of Children RRTI",based on the TCM remedial documents of children RRTI,and following the principles and methods of epidemiology or DME methodology;secondly,to evaluate the quality of clinical researches on RRTI,and then analyze their problems in terms of their research design,implementation and curative effects evaluation with Meta statistic analysis.Clinical research:417 cases of RRTI sick children in non-acute infective stage were selected as research objectives.With the use of epidemiology methods,the following information were collected and recorded into data base by questionnaire:the general and prospective information of sick children, the four physical examinations in TCM,clinical symptom in Western Medicine, and the immunoglobulin,alexin,T cell subset figures of some patients.All indexes were analyzed in terms of frequency,clustering.The distribution of symptom complex in TCM was generalized and the basic syndromes and corresponding diagnosis criteria were determined.As to different types of samples,Kruskal-Wallis Test,Cochran-Mantel-Haenszel Test,Variance Test, chi-square Test were used for analyzing the relations among disease types and grading,the four physical examinations in TCM,clinical symptom in Western Medicine,and the immunity index.ResultsDocumentary research:1.Altogether 141 articles were selected as samples for random contract test(RCT).After being scored by Jadad in terms of quality,1 was marked as 3 points;another 27 were marked as 2 points;and the rest 113 were marked as 1 point.The low quality of articles was reflected in the following aspects:(1) Lack of definite inclusive and exclusive criteria,especially criteria for the diagnosis of TCM Syndrome.(2) Fail to attach importance to standardization,stability and monitoring of adverse drug reaction in TCM therapy.(3) Improvement is needed the level of methodology,such as correct application of randomization principle,blind method and statistical method.2.The Meta results show that the odds ratio(OR) falls within 95% credibility interval,no matter in Chinese Materia Medica group,Chinese Patent Medicine group,or Chinese Materia Medica loaded western medicine group, Chinese Patent Medicine loaded with western medicine or western medicine mentioned above,which shows that there is statistical significance between TCM therapy and its curative effect.Clinical research:The types of syndrome and basic features of children Recurrent Respiratory Tract Infection in non-acute infection period in Guangzhou area:(1) Deficiency of lung,and instability in "wei yang":altogether there are 103 cases,accounting for 24.7%.The main syndromes are low and weak cough, shortness of breath,aversion to wind,aversion to cold,cold in hands and feet,spontaneous perspiration,borborygmus,dry mouth,pale complexion, light white tongue,and weak pulse.(2) Deficiency of both lung and spleen along with stagnation:altogether there are 145 cases,accounting for 34.8%.The main syndromes are repeated cough without heal,aversion to wind,hypodynamia,losing appetite, absent-minded,abdominal distension,abdominal pain,dry and hard stool, difficult evacuation of the bowels,sleepless and fret at night,horizontal "shah gen",dry mouth,white fur,thick fur,slippery pulse,thready pulse.(3) Deficiency of spleen and liver sthenia:altogether there are 87 cases, accounting for 20.9%.The main syndromes are complexion turning yellow, absent-mindedness,repeated cough without heal,green "shan gen", sleeplessness and fret at night,irritability,dry mouth,burning sensation of five centers,light white lip,red tongue,wiry pulse.(4) Deficiency of lung and kidney with phlegm:altogether there are 82 cases,accounting for 19.7%.The main syndromes are repeated cough without heal,low and weak cough,sputum with dull and heavy resonance,shortness of breath,spontaneous perspiration,grey complexion,losing appetite, absent-mindedness,black eye ring,unmated hair,nocturia and enuresis at night,sleeplessness and fret at night,slippery pulse,and weak pulse.2.The comparison among the clinical data of all kinds’ syndrome types:(1)In comparing the age stage,overall illness course,disease frequency, disease type,disease course,immunoglobulin,alexin,T cell subsets,repeated cough without heal,expectoration,shortness of breath,hypodynamia and complexion changes of each syndrome,there is no statistical significance in the differences(P＞0.05).(2)There is statistical significance in the difference of the comparison of weak cough of each syndrome(P＜0.05).The statistical significance lies in deficiency of lung,and instability in "wei yang",deficiency of spleen and liver sthenia,and deficiency of lung and kidney with phlegm(P＜0.01). No statistical significance is found in comparison among other groups (P＞0.05).(3) There is statistical significance in the difference of the comparison of aversion to wind and perspiration of each syndrome(P＜0.05) The statistical significance lies in all four types of syndromes(P＜0.05).(4) There is statistical significance in the difference of the comparison of the color and shape of "shah gen"(P＜0.05).The statistical significance lies in all four types of syndromes(P＜0.05).(5) There is statistical significance in the difference of the comparison of black eye ring,nocturia and enuresis,aversion to cold and cold in hands and feet between deficiency of both lung and spleen along with stagnation and the other three types(P＜0.05).There is statistical significance in the difference of the comparison of hair condition between deficiency of both lung and spleen along with stagnation and deficiency of spleen and liver sthenia (P＞0.05).There is statistical significance among other group comparisons (P＜0.05).(6) There is statistical significance in the difference of the comparison of body emaciation,losing appetite,absent-mindedness,abdominal distension, abdominal pain,and borborygmus between deficiency of lung,and instability in "wei yang" and the other three types.(P＜0.05) The statistical significance lies in vomiting for comparison of deficiency of both lung and spleen along with stagnation,deficiency of spleen and liver sthenia,and deficiency of lung and kidney with phlegm(P＜0.05).There is no statistical significance in the difference of the comparison of dry and hard stool(P＞0.05). There is statistical significance among other group comparisons(P＜0.05).(7) There is statistical significance in the difference of the comparison of burning sensation of five centers,dry mouth,sleepless and fret at night between spleen deficiency and liver sthenia and the other three types(P＜0.05). There is no statistical significance among deficiency of lung,and instability in "wei yang",deficiency of both lung and spleen along with stagnation, and deficiency of lung and kidney with phlegm(P＞0.05)(8) There is statistical significance in the difference of the comparison of tongue color between deficiency of lung,and instability in "wei yang" and the other three types and between spleen deficiency and liver sthenia and lung and kidney deficiency along with stagnation(P＜0.05).There is statistical significance in the difference of the comparison of fur among deficiency of lung,and instability in "wei yang",deficiency of spleen and liver sthenia,and deficiency of lung and kidney with phlegm(P＜0.05).There is statistical significance in the difference of the comparison of pulse tracings among deficiency of lung,and instability in "wei yang",deficiency of spleen and liver sthenia,and deficiency of lung and kidney with phlegm, and also among deficiency of both lung and spleen along with stagnation, deficiency of spleen and liver sthenia,and deficiency of lung and kidney with phlegm(P＜0.05).ConclusionsDocumentary research:(1) Meta analysis shows that TCM therapy does have certain degree of effects for children RRTI,but the difference of effect between treatment group and contrast group may due to the low quality of research methods.(2) The analysis of documentary research shows that the research quality of random comparison study of children RRTI by TCM still needs to be improved. The conclusions drawn so far are lack of persuasiveness.Clinical research"(1) There are four types RRTI in non-acute infective stage in Guangzhou" deficiency of lung,and instability in "wei yang";deficiency of both spleen and lung with stagnation;deficiency of spleen and liver sthenia;and deficiency of lung and kidney with phlegm.The main type is the second type.(2) The following criteria is not valuable for syndrome differentiation in TCM:age,overall course of disease,grading of illness,immunity index, repeated coughing without recovery,phlegm,asthma,lack of strength,change of complexion.(3) Cough with low and weak voice,aversion to wind and perspiration are closely related to deficiency of lung,instability in "wei yang" and deficiency of both spleen and lung with stagnation.The followings are important criteria for differentiation of the second and third type" horizontal "shan gen",greenish-yellow complexion,tarnish,physically thin, dull,lacking of appetite,inflated abdominal pain,nausea or vomit,dry and hard stool and borborygmus.The symptoms of dysphoria,dry mouth and pharynx, sleeplessness is for the recognition of the third type.The symptoms of black eye pit,yellow and dry hair,enuresis,and aversion to cold are important for the differentiation the fourth type.The tongue and pulse demonstration can reflect the etiology,nature,location,degree and transformation of diseases.Their function of differentiation is irreplaceable.更多还原