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1、激发试验论文:支气管激发试验在慢性咳嗽病因诊断价值中的探讨【中文摘要】研究咳嗽是内科患者常见症状,慢性咳嗽表现单一,临床诊断病因和治疗难度较大,咳嗽的诊治不力将导致:抗菌药物的滥用;因诊断不清而反复进行各种检查;既增加了患者痛苦,又加重了其经济负担。用强迫震荡技术判断哮喘患者支气管激发试验是可靠的已经得到证实,但对其诊断哮喘的特异性及诊断标准方面尚需要进一步探讨。用Astograph法测定慢性咳嗽患者的气道反应性,并探讨其在慢性咳嗽病因诊断中的临床价值。研究方法中华医学会呼吸病学分会哮喘学组2009年咳嗽的诊断与治疗指南提出慢性咳嗽的诊断标准:(1)咳嗽时间8周;(2)以咳嗽为主或为惟症状;(

2、3)胸部X线检查正常。本研究共收集了自2010年3月至2010年9月期间以咳嗽为主诉242例患者,失访11例,231例患者入选,失访11例患者同纳入研究的231例患者相比,在年龄、性别、疾病情况等方面无显著差异。研究方案经过医院临床医学伦理委员会批准,并取得所有受试者的知情同意。操作方法参照肺功能检查实用指南。1.受试者先测身高、体重,并练习至能熟练掌握配合肺功能检查要领。采用德国耶格公司MasterScreen-PFT肺功能仪进行常规肺通气功能测定,测定3次,误差低于5%,取其最佳值;应用日本CHEST公司Astograph Jupiter-21气道反应性测定仪进行支气管激发试验检测,同时记

3、录最小诱发累积剂量(Dmin),以呼吸阻力增加到基础呼吸阻力(Rrs cont)的2倍且Dmin15做为阳性标准,支气管激动剂为乙酰甲胆碱。2.根据自愿的原则,对15名Astograph法阳性患者应用德国耶格公司生产的APS气雾激发系统再进行标准激发试验,标准激发试验前后用脉冲震荡法(Impulse Oscillomety, IOS)测定呼吸阻抗,该测定与Astographa法激发试验间隔24小时,为避免深呼吸对试验结果的影响,按照吸入乙酰甲胆碱(Mch)、测定呼吸阻抗、第1秒用力呼气量(FEV1)及呼气峰流量(PEF)、再重复以上过程的顺序测定,测定结束后给予沙丁胺醇。3.记录随访患者就诊至

4、诊断治疗半年内病情或疗效变化。结果1.231例患者中支气管激发试验(BPT)阳性117例,阴性114例,阳性率50.6%,不同性别组BPT阳性率和CVA百分比无显著差异(P>0.05),结合进一步检查及治疗效果,确诊为咳嗽变异型哮喘(CVA)110例,小于30岁年龄组CVA比例最高,占慢性咳嗽病因的68.6%,BPT诊断CVA的特异度为94.0%,60岁组CVA比例最低,为23.1%;其余7例BPT阳性慢性咳嗽患者中5例为感染后咳嗽,2例为0级慢性阻塞性肺病(COPD)患者;114例BPT阴性的咳嗽患者分别是上气道咳嗽综合征(UACS)、嗜酸粒细胞性支气管炎(EB)、胃食管反流性咳嗽(G

5、ERC)、服用血管紧张素转化酶抑制剂(ACEI)类药物和不明原因者,其中UACS组41例(17.7%),EB组25例(10.8%),GERC组24例(10.4%),ACEI组22例(9.5%),病因未明2例(0.9%)。2.分别以Dmin值为1unit、3unit、6unit、15unit为临界值,其诊断哮喘的敏感性、特异性不同,以Dmin6unit作为阳性标准时诊断哮喘的敏感性为74.1%,特异性为90.5%。3.IOS测定15例患者,支气管激发试验(BPT)均阳性,经随访证实哮喘患者10例,非哮喘患者5例,标准激发试验前哮喘组(10例)与非哮喘组(5例)患者基础呼吸阻力:脉冲频率为5Hz、

6、20Hz的气道粘性阻力(R5、R20)、周边弹性阻力(X5),及第一秒用力呼气量(FEV1)、呼气峰流速(PEF)间的差异均无统计学意义(P>0.05);标准激发试验后哮喘组(10例)与非哮喘组(5例)患者基础呼吸阻力:脉冲频率为5Hz时的气道粘性阻力(R5)、第一秒用力呼气量(FEV1)、呼气峰流速(PEF)与激发试验前比较均有统计学意义,哮喘组Dmin值也明显低于非哮喘组。4.BPT阳性的三组患者中,Dmin和Cmin不同,CVA组最著小于COPD组和感染后咳嗽组(P<0.001);剂量-反应曲线不同:三组均以吸入生理盐水时Rrs cont为参照,CVA组、感染后咳嗽组和COP

7、D组吸入Mch到达阈值时,Rrs开始上升,但是三组Rrs上升度(Sd)不同,CVA组Rrs呈曲线样上升,吸入BD后迅速下降,剂量-反应曲线形状似等腰三角形,COPD组Rrs上升缓慢,感染后咳嗽组Rrs上升较COPD更慢,接近于BPT阴性受试者的剂量-反应曲线表现。结论1. Astograph法与IOS测定法结果具有一致性,Astograph法有助于气道高反应性病因的诊断。2.支气管激发试验(BPT)诊断CVA的特异度高,因此,在慢性咳嗽患者中筛查CVA患者,利于早期诊断、正确治疗,防止其发展为典型哮喘。3.咳嗽病因繁多,单一患病个体的病因亦可能是多个因素共存,诊治过程中应注意随访,若遇疗效不佳

8、应及时更改治疗方案。【英文摘要】The diagnosis and treatment of cough failure will cause: antimicrobial drugs abuse, For diagnosis of unclear and repeated inspection, Not only to increase the patient suffering, and increased its economic burden. It has been confirmed that duffing forced-oscillation technical judgeme

9、nt asthma patients bronchial proocation tests is reliable, but its specificity of asthma and diagnosis standard still need further discussion.The objective of this study was to detect the airway sensitivity with Astograph method, as well as to explore its significance in the etiological diagnosis of

10、 chronic cough.MethodsChinese Medicine Respiratory Diseases Asthma Study Group Proposed the diagnostic criteria for chronic cough in 2009:(1) Cough time is at least 8 weeks; (2) Cough is main complain or the only symptom; (3) Normal chest X-ray examination. 231 volunteers were involved in this study

11、, According to the criteria of chronic cough diagnostic,231 patients with chronic cough were involved in our study. The test is after the approval of the Hospital Clinical Medical Ethics Committee and obtaining all participants Informed consent.The routine pulmonary function tests were held under th

12、e instruction of Practical Guide for pulmonary function tests,1.Basic clinical characteristics were first, after which the volunteers were taught how to follow our instructions during a pulmonary test. Routine pulmonary function was tested with a spirograph(Master Screen-PFT Jaeger Co, Hoechberg,Ger

13、many) to decide whether a volunteer fit the airway provocation test. The routine pulmonary function tests were held under the instruction of Practical Guide for pulmonary function tests, each volunteer was repeatly tested three times, and the experimental variation should be no more than 5%, from wh

14、ich the best values were chosen; The airway provocation test was held with an astograph (Astograph Jupiter-21, Japan),in which escalatory doses of methacholine was inhaled to provoke constriction of airways. Dmin value were recorded at the same time, When the respiratory resistance increased to twic

15、e of the basic respiratory resistance (Rrs cont) and Dmin15 was a positive standard.2.According to the principle of voluntarily,15 participants whose bronchial provocation test were positive with Astograph were asked to take Spirometry and impulse oscillation measurements before and after the standa

16、rd methacholine provocation test (APS aerosol excitation system, Hoechberg,Germany). The IOS is after the Astograph more than 24 hours.And to avoid the effect of forced expiratory we follow the order: inhaling methacholine, determinating of respiratory resistance、FEV1、PEF and repeat the above proces

17、s. Those whose BPT positive were given inhaled salbutamol after IOS determination.3.Following up the volunteers in- the next 6 months. Results1. Among 231 volunteers involved in our study,117 cases (50.6%)were found BPT positive, while 114 were negative. Among the 117 positive cases.There was no sig

18、nificant difference in male and female group about BPT positive rate and CVA percentage.110 volunteers were diagnosed as CAV, which comprised 68.6% of the total cough cases, and 5 positive cases were diagnosed as postinfectious cough, while the left 2 were COPD patients of zero grade. The highest CA

19、V occurance rate was seen in group aged below 30 years, while the lowest occurance rate(23.1%) was seen in group aged over 60 years. The specificity of BPT was 94.0% to the diagnosis of CVA. In the 110 negative cases,41 cases (17.7%)were diagnosed as UACS,25 cases (10.8%)were diagnosed as EB,22 case

20、s (9.5%)were due to ACEI drugs intake, while the etiological diagnosis of the left 2 cases was still unknown.2. We used 1 unit,3 unit,6 unit,15 unit of Dmin as the critical value. The diagnosis of asthma sensitivity and specificity were different. When we make Dmin 6unit as the positive criteria for

21、 the diagnosis of asthma, the sensitivity was 74.1% and the specificity was 90.5%.3.15 patients received impulse oscillation determination, confirmed by follow-up 10 patients were asthma, and 5 cases were non-asthmatic patients,whose bronchial provocation test were positive, before the standard prov

22、ocative test there was no significant difference in R5, R20, X5,FEV1, FVC, PEF (P>0.05) both in Asthma group (10 cases) and non-asthmatic group (5 cases). After the standard provocative test there was a significant difference in R5, FEV1, PEF both in Asthma group (10 cases) and non-asthmatic grou

23、p (5 cases). Dmin value in asthma group is much lower in non-asthmatic group.4. CVA, postinfectious cough and COPD are the three main causes of chronic cough with positive BPT, but they also have their own characteristics. CVA group had an evident lower Dmin and Cmin than the other two groups(P<0

24、.001). There was also a significant difference in the appearance of dose-resistance curve, mainly in the increasing rate of airway resistance. In CVA group, the resistance increased in a dynamic type, but fell rapidly after inhalation of bronchodilators, and the dose-resistance curve looked like an

25、isosceles triangle, however, in COPD and postinfectious goup, the resistance increased slowly, especially in the postinfectious goup, it even showed an appearance similar to BPT negative curve.Conclusion1. Astograph and IOS were the same predictive value in BPT. Astograph method helps to diagnose the cause of airway hyperresponsiven

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