上海交通大学硕士学位论文慢性阻塞性肺疾病并发持续喘息的临床研究姓名：祁卉卉申请学位级别：硕士专业：内科学（呼吸病学）指导教师：金先桥200804292008 届上海交通大学硕士论文 1慢性阻塞性肺疾病并发持续喘息的临床研究 摘 要 目的：探讨慢性阻塞性肺疾病患者并发持续喘息与痰真菌培养阳性之间的相关性； 探讨慢性阻塞性肺疾病患者痰真菌培养阳性的危险因素。 方法：收集 2005 年 1 月 1 日至 2007 年 12 月 31 日期间于上海市第一人民医院、中山医院、华东医院呼吸科就诊住院的符合入选标准的病例组和对照组患者的病史资料进行回顾性分析。 结果：共收集到符合入选标准的病例组 35 例，对照组 43 例。两组患者的痰病原学检测结果不同，病例组 35 例中 32 例（91.4%）痰真菌培养阳性，而对照组 43 例中 11 例（25.6%）痰真菌培养阳性，两组比较差异显著（P=0.000） ；相关分析提示痰真菌培养阳性和持续喘息间存在相关性(r=0.658，P=0.000),痰真菌培养阳性是持续喘息的危险因素（OR=31.030，95%CI: 7.905121.799） 。在真菌的菌种构成方面，病例组32 例中曲霉菌 12 例，对照组 11 例中未检出曲霉菌，曲霉菌在两组中分布差异有统计学意义（P0.05） 。病例组中抗真菌治疗在症状缓解方面较未抗真菌治疗者差异有统计学意义（P0.05） 。以痰真菌培养结果分组，痰真菌培养阳性组与阴性组在性别、年龄、糖尿病史、吸烟史、雾化吸入史、累计口服糖皮质激素及是否有糖皮质激素吸入史方面差异无2008 届上海交通大学硕士论文 2统计学意义（P0.05） ，在抗生素应用种类、抗生素使用时间、累计静脉使用糖皮质激素剂量和糖皮质激素使用时间等方面差异显著（P0.01） 。多因素分析提示抗生素和糖皮质激素使用时间长及静脉大量使用糖皮质激素是痰真菌培养阳性的危险因素（P0.05） 。 结论：慢性阻塞性肺疾病患者并发持续喘息与真菌在气道内持续存在相关。长期大量糖皮质激素的使用及长期广谱、超广谱抗生素的联合使用或更换过于频繁是下呼吸道真菌持续存在的危险因素。 关键词： 慢性阻塞性肺疾病，持续喘息，真菌，危险因素 2008 届上海交通大学硕士论文 3CLINICAL ANALYSIS OF PERSISTENT WHEEZING IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE ABSTRACT Objective: To analyze the morbidity, clinical manifestation and the etiology of the persistent wheezing in patients with chronic obstructive pulmonary disease and the risk factors of the positive result in the fungi culture of the sputum. Methods: The case data met the recruit criteria was collected from patients diagnosed and hospitalized in the respiratory departments of the Shanghai First Peoples Hospital, Zhongshan Hospital and Huadong Hospital from Jan 2005 to Dec 2007. A retrospective study was taken to analyze the case-control study. Results: During the period, 35 cases were collected in the case group and 43 cases in the control group; 32 (91.4%) cases with persistent wheezing 2008 届上海交通大学硕士论文 4more than 4 weeks in the case group had positive sputum culture of fungi, while in the control group there were 11 (25.6%) cases had the positive result; The difference of the results of sputum culture of fungi between 2 groups was significant (P=0.000),and the persistent wheezing significantly correlated with the positive sputum culture of fungi (r=0.658，P=0.000, OR=31.030, 95%CI: 7.905121.799). The composition of fungi was significantly different in 2 groups (P3)-beta-D-glucan in early diagnosis of invasive pulmonary aspergillosis in a patient with chronic obstructive pulmonary disease. J Med Microbiol. 2003 Nov;52(Pt 11):1031-2 14 Murray C, Lopez A: Mortality by cause for eight regions of the world: global burden of disease study. Lancet 1997; 349: 12691276 15 Seemungal T, Donaldson G, Paul E, Bestall J, Jeffries D, Wedzicha J: Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157: 14181422 16 Sethi S: Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000; 117(Suppl.): 380S-385S 17 Wilson R: Bacteria, antibiotics and COPD. Eur Respir J 2001;17: 9951007. 18 侯天文,陈兴,张健 等，COPD 患者急性发作期下呼吸道病原菌群分布与耐药分析, 中国感染控制杂志 2006，5（2） ，174-175 19 孟自力, 慢性阻塞性肺疾病急性发作期痰菌培养及耐药性分析.中原医刊, 2001, 28(11) : 27 20 周忠，张娟，鲁伟, COPD 急性发作期下呼吸道病原菌感染分析.临床肺科杂志 2007，12 (11):1243-1244 21 Soler N, Agust C, Angrill J et al. Bronchoscopic validation of the significance of sputum purulence in severe exacerbations of chronic obstructive pulmonary disease. Thorax. 2007 Jan;62(1):29-35 22 Blasi F, Damato S, Cosentini R et al. Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. Thorax. 2002 Aug;57(8):672-6 23 刘玲,李晓静，老年慢性阻塞性肺疾病急性加重期肺部真菌感染的临床分析，中国临床保健杂志，2007，10（6） ，597-599 2008 届上海交通大学硕士论文 33 24 黄隽敏， 徐爱晖， COPD 患者继发肺部真菌感染 57 例临床分析， 临床肺科杂志，2008，13（1） ，46-47 25 Kosc, Chen KY, Hsueh PR, et al. Fungal empyerna thoracis an emerging clinical entity. Chest, 2000, 117 (6) : 1672 - 1678 26 王晓虹,罗立.慢性阻塞性肺病继发肺部真菌感染 41 例临床分析, 临床肺科杂志，2005,10(5),589-590 27 Ader F, Nseir S, Guery B et al. Acute invasive pulmonary aspergillosis in chronic lung disease-a review. Rev Mal Respir. 2006 Jun;23(3 Suppl):6S11-6S20 28 Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007 Oct;30(4):782-800 29 中华内科杂志编辑委员会. 侵袭性肺部真菌感染的诊断标准与治疗原则(草案) ， 中华内科杂志, 2006, 45: 697 -700. 30 Pittet D,Huguenin T., Dharan S.et al .Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996,154, 541544 31 Garcs Jarque JM, Terradas Robledo R, Alvarez-Lerma F et al. Lung aspergillosis. Role of the corticoids as associated risk factor in the patient with chronic bronchitis. Rev Clin Esp. 2003 Oct;203(10):472-4 32 钱小顺,朱元珏,许文兵,等. 127 例肺部真菌感染的临床分析. 中华结核呼吸杂志, 2000 , 23 :417 33 Khasawneh F, Mohamad T, Moughrabieh MK, et al.Isolation of Aspergillus in critically ill patients: a potential marker of poor outcome. J Crit Care. 2006 Dec;21(4):322-7 34 Garnacho-Montero J, Amaya-Villar R, Ortiz-Leyba C et