Research On Characteristics Of Bronchial Asthma In Xinjiang Based On Modern Literature, Case Review, Key Points Of TCM Syndrome Elements And Gene Polymorphism

Objectives:1. To summarize clinical features and biological characteristics of Chinese, Uygurand Western medicines of bronchial asthma in Xinjiang through the analysis of theresearch group on basis of bronchial asthma in Xinjiang and relevant clinical researchesunder the theoretical guidance of Chinese, Uygur and Western medicines; find “crosspoints” of three medicines in the understanding of bronchial asthma in Xinjiang andclarify abnormal changes of its biological foundation.2. To conduct retrospective analysis on clinical cases of bronchial asthma andexplore risk factors, clinical features, diagnosis and treatment status and TCM syndromedistribution law.3. To carry out research on key points of TCM syndrome elements and genepolymorphism of bronchial asthma in Xinjiang, summarize the distribution law of keypoints of TCM syndrome elements and characteristics of gene polymorphism and thus laya foundation for developing an “individual” diagnosis and treatment program ofbronchial asthma in Xinjiang.Methods:1. Literatures related to asthma and regarding Western, Chinese and Uygur medicinespublished by this research group from1989to2009were searched in CNKI, SWIC (VIP) and CJFD and summarized.2. A query was made in the “comprehensive inquiry” column in case managementmodule in HIS system of the hospital with the following search conditions:“dischargediagnosis”=“asthma or bronchial asthma” and “admission time”=from00:00, January1,2011to24:00, December31,2012.735cases of inpatients meeting these conditionswere inquired, including47cases of repeated hospitalization which were therebyeliminated.688cases of patients of bronchial asthma were arranged according to theascending order of admission number and the former305cases were selected for analysis.Admission numbers of selected cases were input one by one in Haohan electronic casesystem for relevant information inquiry and meanwhile the information collection formwas filled in.3. A survey of TCM syndrome elements was conducted on patients of asthma withthe method of cross-section survey of epidemiology according to the principle ofepidemiology and TCM syndrome questionnaire was filled in. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR (ASP)were used to test TNF-α-308and IL-13gene2100A/G mutation site polymorphism.Statistical treatment was conducted with SPSS17.0statistical package. Measurement datawere expressed as mean±standard deviations and used t test. Enumeration data used x2test. The genotype distribution frequency and allele frequency at each site in each groupwere first counted and its conformance to Hardy-Weinberg balance was confirmed. Forgenotype, direct counting method was used.Results:1．Clinical features and biological characteristics of bronchial asthma in XinjiangClinical features of Western medicine show that asthma in Xinjiang Uygur isdominated by infectivity; infection is both pathogenic factor and inducing factor andespecially obvious in severe asthma; the older, the longer the course of disease and theeasier to suffer from severe asthma; with poor control and repeated attack, mild andmoderate asthma will finally develop into severe asthma.Clinical features of Chinese medicine show that the pathogenesis of bronchialasthma in Xinjiang is mainly cold; pathogenic excess is mainly “phlegm” and “stasis”;weakened body resistance is mainly caused by “deficiency of kidney-yang”;differentiation of symptoms and signs for classification of syndrome is mainly asthmadue to cold and phlegm stasis due to deficiency of kidney (asthma due to deficiency). Each Chinese medicine classification has “long-standing phlegm”.Clinical features of Uygur medicine show that,“corrosive” liquid produced in heador nasal cavity during cold or “allergy”, which is caused by throat and airway infectionand environmental factor etc., plus abnormity of body fluid caused by genetic factor andairway stimulation etc., cause airway inflammation and increased sensitivity of airwaynerve fiber, thus inducing asthma. According to the theory of Uygur medicine, asthmahas four types-abnormal savda, abnormal phlegmatic temperament, abnormal bloodquality and abnormal bile quality. Abnormal savda asthma is severe. Among all types ofasthma, abnormal savda asthma occurs at the maximum age with the severest state ofillness and the most complicated pathogenesis. With the increase of age, people are easierto suffer from abnormal savda asthma.Biological characteristics of Western medicine show that, in patients of bronchialasthma in Xinjiang, CD4/CD8, CD11b, CD11b/CD18and CD62Pgradually increase,activation-induced cell death slows down and CS, ACTH and CRH gradually decrease;allergen specific IgE antibody positive rate of Uygur patients of bronchial asthma inXinjiang is significantly lower than the Han nationality in the south and their serum ECP,T-IgE and S-IgE levels are significantly higher than non-asthma patients; meanwhile,their Gly16homozygote genotype frequency is significantly higher than the healthycontrol group. Compared to other (mild and moderate) asthmas, in severe asthma,anomalous changes of lymphocyte subpopulation, medium and endogenous cortisol aremore obvious; expression of CD62Pon the surface of platelet membrane, ET-1, PAI-1andFIB significantly increase, APTT and PT time decreases and t-PA content and activitygreatly reduce. Compared to other asthmas, in severe asthma in Xinjiang Uygur, ECPvalue is the highest and anomalous changes of S-ECP and IgE are more obvious;meanwhile, gene polymorphic Gly/Gly genotype distribution frequency at β2-AR16siteand polymorphic CT genotype distribution frequency in IL-4gene promoter regionsignificantly increase.Biological characteristics of Chinese medicine show that, compared to other TCMsyndrome asthma, in phlegm stasis asthma due to deficiency of kidney, anomalouschanges of lymphocyte subpopulation, medium and endogenous cortisol are moreobvious.Biological characteristics of Uygur medicine show that, compared to other Uygurmedicine syndrome asthmas, in abnormal savda asthma, anomalous changes oflymphocyte subpopulation, medium and endogenous cortisol are more obvious; expression of CD62Pon the surface of platelet membrane, ET-1, PAI-1and FIBsignificantly increase, APTT and PT time decreases and t-PA content and activity greatlyreduce; the variation of gene polymorphism at IL-13intron3+1923site might increase theoccurrence risk of abnormal savda asthma; IL-4gene589(C/T) site polymorphism andabnormal savda asthma have certain correlation.The interaction of Chinese, Uygur and Western medicines shows that severe asthma,phlegm stasis asthma due to deficiency of kidney and abnormal savda asthma havecertain interaction, manifested in old age, long course of disease, relapse of illness andcomplicated pathogenesis. Their syndromes are overlapped. All of them have increasedCD11b/CD18, slowed-down activation-induced cell death and CS, ACTH and significantlyreduced endogenous cortisol.Compared to phlegm stasis due to deficiency of kidney and abnormal savda asthma,though patients of other types of asthma do not have clinical manifestations of phlegmstasis due to deficiency of kidney or abnormal savda, their biological foundations such asimmuno-endocrine network system dysfunction have “latent” change similar to phlegmstasis due to deficiency of kidney and abnormal savda asthma. Therefore, its essencemight still belong to the scope of phlegm stasis due to deficiency of kidney or abnormalsavda.2．Retrospective analysis was conducted on305cases of bronchial asthma,including111male cases and194female cases, and236cases of Han nationality,38cases of Uygur,19cases of Hui nationality and12cases of other nationalities, with anaverage age of52.90±16.93and average length of stay of11.41±4.80days. In78cases,wheezing could be heard in lung, accounting for25.57%.There were9cases of male and2cases of female below18, respectively accountingfor81.81%and18.19%;21cases of male and23cases of female between18and40,respectively accounting for47.73%and52.27%;49cases of male and104cases offemale between40and60, respectively accounting for32.03%and67.97%;32cases ofmale and65cases of female≥60, respectively accounting for32.99%and67.01%.52cases had an obvious pathogenic factor, accounting for17.05%, including16cases of exogenous factor (unknown specifically),14cases of simple genetic factor,8cases of pungent smell,3cases of food, respectively2cases of heredity accompanied byexogenous factor, pollen, house dust and dust and respectively1case of heredityaccompanied by exercise, heredity accompanied by organic fiber, pollen and radiotherapy,pollen and food and tiredness.186cases had an obvious incentive, accounting for60.98%, including162cases of external infection accounting for87.10%,16cases ofpsychological factor accounting for8.60%,13cases of pungent odor accounting for6.99%,7cases of strenuous exercise or tiredness accounting for3.76%,2cases ofmedicine accounting for1.08%,1case of RTI accounting for0.55%and1case ofsatiation accounting for0.55%.299cases had an explicitly recorded initial symptom, including202cases of cough,54cases of choking sensation in chest,22cases of dyspnea,8cases of gasp,5cases ofpalpitation,2cases of pharyngalgia,2cases of fever and respectively1case ofpharyngeal itching, nasal obstruction, chest pain and dyspnea.152cases had explicitlyrecorded symptom increase or onset time, including56cases after exercise accountingfor36.83%,40cases at night accounting for26.32%,26cases after pungent smellaccounting for17.11%,12cases after pungent smell and exercise accounting for7.89%,10cases after getting up in the morning and exercising accounting for6.58%,5casesafter exercise and at night accounting for3.29%and respectively1case after satiationand exercise, after getting up in the morning and in cold air, and after exercising and incold air accounting for0.66%;58cases with the history of smoking accounting for19.02%,242cases without the history of smoking accounting for79.34%and4caseswithout telling the history of smoking accounting for1.64%;110cases with the history ofallergy accounting for36.07%;19cases with specific family history of asthmaaccounting for6.23%;207cases with explicitly recorded complication accounting for67.88%;138cases experiencing blood gas analysis test accounting for45.25%;296casesexperiencing blood routine examination accounting for97.05%;262cases experiencingcoagulation function examination accounting for85.90%; and89cases experiencingc-reactive protein examination accounting for29.18%.265cases had explicitly recorded coated tongue pulse manifestation, accounting for86.89%. According to Chinese tradition medicine type, there were74cases of lungimpairment due to dryness evil accounting for27.92%,70cases of asthma due to coldaccounting for26.42%,48cases of wind-phlegm asthma accounting for18.11%,31casesof asthma due to heat accounting for11.70%,19cases of deficiency of lung and kidneyaccounting for7.17%,13cases of asthma due to deficiency accounting for4.91%,6cases of deficiency of lung, spleen and vital energy accounting for2.26%and4cases offrigiopyretic asthma accounting for1.51%.In terms of the therapeutic status,71.48%patients used glucocorticoid,65.57%patients used inhaled glucocorticoid+long-acting beta receptor agonist (ICS+LABA), 62.62%patients used aminophylline drugs,50.16%patients used LTRA,46.56%patientsused antibiotics,41.97%patients used anticholinergic drug,33.77%patients usedantihistamine drug,32.46%patients used short-acting β2receptor agonist (SABA) and17.70%patients used acid suppression drug. In terms of drug delivery route, aerosolinhalation, oral medication and intravenous administration of glucocorticoid respectivelyaccounted for45.57%,4.92%and28.20%; inhalation of short-acting β2receptor agonistaccounted for32.46%; inhalation of anticholinergic drug accounted for41.64%;inhalation of ICS+LABA accounted for65.25%; oral and intravenous administration oftheophylline respectively accounted for4.92%and58.36%; oral and intravenousadministration of antibiotics respectively accounted for15.08%and46.23%; oraladministration of antihistamine drug and LTRA respectively accounted for33.11%and54.75%; oral and intravenous administration of acid suppression drug respectivelyaccounted for9.84%and17.70%; oral administration of traditional Chinese medicineaccounted for86.23%; treatment with invasive breathing machine accounted for0.33%;treatment with noninvasive breathing machine accounted for1.64%; drug combinationaccounted for95.09%;50cases simply taking traditional Chinese medicine decoctionaccounted for16.39%;140cases taking traditional Chinese medicine decoction pluscream formula accounted for45.90%;31cases taking traditional Chinese medicinedecoction plus free decoction and cream formula accounted for10.16%;72.46%patientswere subject to treatment by Chinese herbs and42.95%patients were subject to thetreatment of application of Chinese herbs.3．Document research on TCM syndrome elements of bronchial asthma shows that19syndrome elements constitute bronchial asthma, mainly including phlegm (42.89%),fever (34.53%), deficiency of vital energy (27.64%) and deficiency of yin (15.31%) andaction targets are mainly lungs (82.84%) and kidney (22.22%). Clinical survey shows that,for the period of onset of bronchial asthma in Xinjiang, the frequency of occurrence ofwhich ranks among the top three, disease factors are phlegm, deficiency of yin and coldand disease locations are lungs, surface and heart.4. By comparison between asthma group and normal control group, Uygur asthmagroup and Uygur normal control group, Han asthma group and Han normal control group,Uygur normal control group and Han normal control group, two genotypes (wild type andmutant type) of TNF-α-308and allelic genes had differences in distribution withoutstatistical significance (P＞0.05). By comparison between asthma group and normalcontrol group, Uygur asthma group and Uygur normal control group, IL-13gene 2100A/G mutation site genotype frequency had differences with statistical significance,but allelic gene frequency had no statistical significance. By comparison between Hanasthma group and Han normal control group, Uygur normal control group and Hannormal control group, IL-13gene2100A/G mutation site genotype and allelic gene haddifferences in distribution without statistical significance (P＞0.05).Conclusions:1．Clinical characteristics of bronchial asthma in Xinjiang in Chinese, Uygur andWestern medicines1.1Western medicine research shows that infection is closely related to themorbidity of bronchial asthma in Xinjiang. Infection is both pathogenic factor andinducing factor and especially obvious in severe asthma; the older, the longer the courseof disease and the easier to suffer from severe asthma.1.2Chinese medicine research shows that the pathogenesis of bronchial asthma inXinjiang is mainly cold; pathogenic excess is mainly “phlegm” and “stasis”; weakenedbody resistance is mainly caused by “deficiency of kidney-yang”; differentiation ofsymptoms and signs for classification of syndrome is mainly asthma due to cold andphlegm stasis due to deficiency of kidney (asthma due to deficiency). Each Chinesemedicine classification has “long-standing phlegm”.1.3Uygur medicine research shows that “corrosive” liquid produced in head ornasal cavity during cold or “allergy”, which is caused by throat and airway infection andenvironmental factor etc., plus abnormity of body fluid caused by genetic factor andairway stimulation etc., cause airway inflammation and increased sensitivity of airwaynerve fiber, thus inducing asthma. According to the classification, abnormal savda asthmais severe, which occurs at the maximum age with the severest state of illness and the mostcomplicated pathogenesis.2．In this survey, there were more female asthma patients than male patients andthere were most patients between40and60. The initial symptom cough has the highestproportion, followed by chocking sensation in chest and dyspnea. Clinical symptomincrease is commonly seen after exercise, followed by at night and pungent smell.Allergic rhinitis is closely related to the morbidity of asthma. There were30cases ofasthma accompanied by allergic rhinitis, accounting for9.84%. Evil among the sixexternal factors which cause diseases is one of the important reasons for onset of asthma.Cold and dryness evil are main causes of bronchial asthma in Xinjiang. In TCM syndrome, the period of onset mainly involves lung impairment due to dryness evil,followed by asthma due to cold. Patients of asthma due to deficiency and deficiency oflung and kidney are old. Patients of asthma below18generally have asthma due to heat.Patients of asthma between18and60mostly have lung impairment due to dryness evil.Patients above60mostly have asthma due to cold. Western medicine diagnosis andtreatment of bronchial asthma basically meet requirements of the guideline, but there arestill problems such as excessive types of drug combination and higher proportions ofantibiotics and intravenous administration of hormone. Chinese medicine treatmentmainly involves warming lung for dispelling cold, nourishing Yin and moistening dryness,tonifying qi and strengthening exterior and tonifying kidney, invigorating the circulationof blood and reducing phlegm, specifically including the comprehensive diagnosis andtreatment program of simultaneous internal and external treatment-traditional Chinesemedicine decoction, free decoction, traditional Chinese medicine cream formula andapplication.3. It is found that Western medicine of severe asthma, Chinese medicine of phlegmstasis asthma due to deficiency of kidney and Uygur medicine of abnormal savda asthmahave certain interaction, manifested in severe state of illness, long course of disease, oldage, overlapped syndrome and more obvious immune and endocrine disorder.4. Disease locations of syndrome in the period of onset of bronchial asthma inXinjiang mainly involve lungs, surface and heart; disease factors are mainly phlegm,deficiency of yang and cold. Its onset is irrelevant with TNF-α-308polymorphism butrelated to IL-13gene2100A/G mutation site polymorphism.5. A new idea is put forward, i.e. biological characteristics of Chinese and Uygurmedicines and other syndrome types of asthma have “latent” change similar to phlegmstasis asthma due to deficiency of kidney in Chinese medicine and abnormal savdaasthma in Uygur medicine. To prevent the development of asthma into phlegm stasisasthma due to deficiency of kidney or abnormal savda asthma, the treatment should beshifted forward to realize “prevention first, early treatment and prevention of pathologicalchanges” and thus effectively control recurrence of asthma and/or exacerbation.