吸烟与呼吸疾病

治 病 先 戒 烟（呼吸篇）,北京市海淀医院 呼吸内科 姚彬 主任医师,目 录,吸烟对呼吸系统的危害,戒烟的益处,认识烟草依赖和戒断综合征,戒烟方法,“明知有害，照吸不误，您可能是对烟草中的尼古丁成瘾啦，这是一种慢性病，得治疗！” 对每一位患者，王辰大夫都会问吸烟的情况。,中国工程院院士、中日医院院长，王辰大夫非常重视我国的控制吸烟问题，他说：“吸烟为致病之首恶，控烟为防病之首善”。,1. 2007年版中国临床戒烟指南（试行本）2. Sandler DP, et al. J Natl Cancer Inst. 1993;85(24):1994-2003. 3. Crane MM, et al. Cancer Epidemiol Biomarkers Prev. 1996;5(8):639-644. 4. Miligi L, et al. Am J Ind Med. 1999;36(1):60-69. 5. Roman GC. Cerebrovasc Dis. 2005;20(Suppl 2):91-100. 6. Willigendael EM, et al. J Vasc Surg. 2004;40:1158-1165.,吸烟可以导致多系统多种疾病,长期吸烟对肺的影响,吸烟15年后的肺,吸烟前的肺,吸烟可使哮喘发作更严重,与从不吸烟者和戒烟者比吸烟者哮喘发作明显更多严重度评分明显更高,a At rest in the last 12 months.b Relationship between attacks of breathlessness and smoking. c Severity score for asthma was established using an a priori decisional tree.d Strength of the relationship betweenseverity score and smoking. The 3 classes were coded 1, 2, and 3 for quantitative analysis. Severity score was adjusted for age, sex, and educational level.,Siroux et al. Eur Respir J. 2000;15(3):470-477.,a All P values reflect difference in pulmonary function within groups before and after beclomethasone therapy. b AM PEF= AM peak expiratory flow; c PC20 Mch=PC20 methacholine,Lazarus et al. Am J Respir Crit Care Med. 2007;175(8):783-790.,吸烟使哮喘患者对于吸入激素药物的治疗反应降低,什么是COPD？,活动后呼吸困难,休息时呼吸困难,吸烟引发COPD,吸烟加重COPD病情,吸烟是COPD患者的主要死亡原因,研究显示COPD患者有6成以上死于吸烟。,慢性支气管炎的发病率,持续吸烟者慢性支气管炎的累计发病率为42%而戒烟者和从不吸烟者分别只有26和22,Pelkonen et al. Chest. 2006;130(4):1129-1137.,a Cumulative incidence. b1711 middle-aged men belonging to 2 groups were followed up for up to 40 years.,吸烟与肺癌的关系,吸烟时间越长，吸烟量越多，患肺癌的危险性越高,肺癌死亡率(/千人年),资料来源： Doll, R et al (1994) BMJ 309.,烟草和烟雾中的有毒、有害物质,4000种化学物质, 250种有毒或致癌物质1,1. National Toxicology Program. 11th Report on Carcinogens; 2005. 2. Surgeon Generals Report. The Health Consequences of Smoking; 2004.,吸烟广泛参与肿瘤发生、发展与侵袭转移,吸烟,受体结合,吸烟/尼古丁成瘾,正常细胞生长调控缺失,抑癌基因失活其他,致癌源肿瘤促进剂基因增强子甲基化,代谢激活,致癌源,持续编码错误,DNA合成异常,解毒代谢,RAS, TP53其他基因突变,癌症,AKT, PKA激活其他变化,凋亡下降血管生成上升细胞转化上升,DNA修复,致癌性增强,排出体外,凋亡,正常DNA,Adapted from Devita, Hellman & Rosenbergs Cancer: Principles & Practice of Oncology, 8th Edition-Tobacco,目 录,吸烟对呼吸系统的危害,戒烟的益处,认识烟草依赖和戒断综合征,戒烟方法,PC20 AMP mg/mL-1 c,PC20 Mch mg/mL-1 b,a P.05 before quitting vs 12 months after quitting. bPC20 Mch=provocative concentration of methacholine (Mch) that induces a 20% fall in FEV1. c PC20 AMP=provocative concentration of adenosine-5 monophosphate (AMP) that induces a 20% fall in FEV1.,Willemse et al. Eur Respir J. 2004;24(3):391-396.,戒烟可以改善支气管的高反应性,aAdjusted for sex, age, clinic, body mass index, baseline cigarettes/day, nonwhite race, dust/fume exposure, years of education, lung problems before 16 years of age, FEV1 % predicted, bronchodilator response %, Mch reactivity, and baseline symptoms. Mean prevalence at first through the fifth annual visits. bFor all variables evaluated.,基础症状,咳嗽3月/年,咳痰3月/年,喘息,呼吸困难,干预,一般保健,Reported Symptoms at Baseline (%)a,P.00001b,43.6,42.2,55.4,51.6,58.7,64.9,60.6,64.7,0,10,20,30,40,50,60,70,Kanner et al. Am J Med. 1999;106(4):410-416.,戒烟改善呼吸系统基础症状,Chaudhuri et al. Am J Respir Crit Care Med. 2006;174(2):127-133.,32 Smokers with asthma were given the option to quit or continue smoking. Both groups underwent spirometry and induced sputum at baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical beclometasone, airway response to oral prednisolone, and sensitivity of peripheral blood lymphocytes to corticosteroids were measured before smoking cessation and at 6 wk.,戒烟使哮喘患者肺功能明显改善,* Asthma control score adapted from American Thoracic Society. Guidelines for the evaluation of impairment/disability in patients with asthma.,Am J Respir Crit Care Med Vol 174. pp 127133, 2006,P0.05,戒烟使哮喘控制评分显著改善,Kanner RE, Connett JE, Williams DE, et al. Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease: the Lung Health Study. Am J Med. 1999;106(4):410-416.,本研究评价5年内35-60岁的早期COPD患者(n=5,887)戒烟对COPD症状改善的作用,进行戒烟干预，5年内COPD患者基础症状加重的比例60%,戒烟可显著减少COPD症状急性发作,P0.0001,P0.0001,P0.0001,P0.0001,延缓COPD病情进展，只有戒烟！,戒烟是迄今为止唯一经证实可有效延缓肺功能进行性下降的措施,戒烟后呼吸困难症状可迅速缓解,长时间戒烟可延缓COPD患者病情进展,累计生存可能 (%),5,10,15,20,25,30,诊断慢性支气管炎后的随访年数,Based on the Cox model (P.001), adjusted for age, pulmonary function, and the study year of examination at which chronic bronchitis was diagnosed for the first time. Decrease in daily smoking was calculated as a change in the mean number of cigarettes per day.a On average, smokers had reduced their smoking by 13 cigarettes (SD, 5); their previous consumption had been 22 cigarettes (SD, 5). b Subjects smoked on average 19 cigarettes per day (SD, 6).,Pelkonen et al. Chest. 2006;130(4):1129-1137.,减少吸烟可延长慢性支气管炎患者生存期,Godtfredsen NS, Prescott E, Osler M. Effect of smoking reduction on lung cancer risk. JAMA. 2005;294(12);1505-1510.,重度吸烟者,减量吸烟者,轻度吸烟者,戒烟者2,从不吸烟者,戒烟者1,0.09,0.17,0.44,0.5,0.73,0,0.2,0.4,0.6,0.8,1,研究对9714名参与者进行了为期31年的随访，观察吸烟减量与肺癌发生的关系。戒烟者1指 研究开始时未戒烟，随访时戒烟；戒烟者2指研究开始和随访时一直戒烟。重度吸烟者：15 支/天，减量吸烟者：以前15 支/天，减量至少一半；轻度吸烟者：114支/天。,肺癌风险比（95%的可信区间）,戒烟，远离肿瘤的重要干预措施,戒烟以后短期内就可获益,肺功能改善：咳嗽、气管充血、劳累和气短减轻,心肌梗死的风险下降,血中一氧化碳 (CO) 明显下降,血压降至吸最后一支烟之前的水平，手和脚的温度升至正常,戒烟时间阶梯,20分钟,8小时,24小时,3个月,1. ACS, 20032. CDC. Surgeon General Report 20043. American Cancer Society. Guide to Quitting Smoking. Available at: . Accessed June 2006.,戒烟时间越长获益越多,冠心病危险与从未吸烟者类似,肺癌危险为持续吸烟者的30% - 50%,中风危险降低到从未吸烟者的水平,冠心病额外危险降低50%,戒烟时间阶梯,1年,5年,10年,15年,1. ACS, 20032. CDC. Surgeon General Report 20043. American Cancer Society. Guide to Quitting Smoking. Available at: . Accessed June 2006.,35岁 40岁 50岁 60岁,如果开始戒烟，寿命可以找回来1,35岁戒烟，找回10年40岁戒烟，找回9年50岁戒烟，找回6年60岁戒烟，找回3年,1. Doll. R. et al: BMJ 328(7455): 1519, 2004,10年,9年,6年,3年,目 录,吸烟对呼吸系统的危害,戒烟的益处,认识烟草依赖和戒断综合征,戒烟方法,烟草依赖是一种慢性疾病,1998年WHO决议将烟草依赖作为一种疾病列入国际疾病分类（第10版）（ICD-10）(F17.2, 属精神神经障碍)，确认烟草是目前对人类健康的最大威胁,2007年中国临床戒烟指南,尼古丁 烟草成瘾的最主要物质,Jarvis MJ. BMJ. 2004; 328:277-279. 2. Picciotto MR, et al. Nicotine and Tob Res. 1999: Suppl 2:S121-S125.,戒断综合征 戒烟失败的根本原因,1. Hughes JR et al. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004; 99(1): 29-382. Coleman T. Use of simple advice and behavioural support. BMJ Books, Blackwell Publishing 2004; 328: 397-399,戒断综合征,交感神经系统波动 (不可预测的兴奋/抑制),心功能亢进/抑制,瞳孔散大/缩小,支气管扩张/收缩,肠道功能抑制/亢进,戒断综合征 干扰基础疾病的诊断和治疗,目 录,吸烟对呼吸系统的危害,戒烟的益处,认识烟草依赖和戒断综合征,戒烟方法,干戒的特点 最原始的，没有办法的办法,没有方法采用率高适用率低失败率高,流行病学数据显示，试图使用Cold turkey干戒方法的戒烟者，戒烟1年之后只有不到3%的人保持不吸烟 ，能够戒断成功的人大多数都要花710次的尝试。,Hughes JR et al. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004; 99(1): 29-38,戒烟药物可有效帮助缓解戒断症状,长效1,2 贴片短效1,2 咀嚼制剂 吸入剂 鼻喷雾 舌下含片,酒石酸伐尼克兰片(畅沛TM),尼古丁乙酰胆碱受体部分激动剂2,尼古丁替代疗法(NRT)1,2,盐酸安非他酮 去甲替林,抗抑郁药物2,1. Stead L, Lancaster T. Nicotine replacement therapy for smoking cessation: Cochrane systematic review.Int J Epidemiol. 2005;34:1001-1003. 2. Henningfield JE, Fant RV, Buchhalter AR, et al. Pharmacotherapy for Nicotine Dependence. CA Cancer J Clin. 2005;55:281-299. 3. Jorenby D E, Taylor Hays J, Rigotti N A, et al. Efficacy of Varenicline, an alpha4beta2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation: A Randomized Controlled Trial. The Journal of the American Medical Association 2006; 296:56-634. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation: A Randomized Controlled Trial. The Journal of the American Medical Association 2006; 296:47-55,畅沛TM独特的双重作用机制1,2,1. British Medical Journal. 2004;328;277-2792. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Confer