目的回顾性分析小剂量环孢素A（Cs A）单药治疗特发性膜性肾病的疗效。方法回顾性分析2008年9月至2015年12月北京大学第一医院收治的Cs A[1~3 mg/（kg·d）]单药治疗的特发性膜性肾病患者,收集临床随访资料。统计完全缓解率、部分缓解率、无效率,缓解后的复发情况。结果 36例患者符合入选标准。Cs A单药治疗时间为（15.56±8.86）个月,随访均大于12个月。治疗6个月缓解率67.7%（24/36）,其中完全缓解11.1%（4/36）,部分缓解55.6%（20/36）;治疗12个月缓解率58.3%（21/36）,其中完全缓解25.0%（9/36）,部分缓解33.3%（12/36）;5例（20.8%）部分缓解患者复发;在长期随访中,42.9%的缓解患者复发。结论小剂量环孢素A单药治疗特发性膜性肾病有效,可避免联合糖皮质激素治疗的副反应;但应注意缓解后有一定比例的复发。

Marsdenia tenacissima (Roxb.) Wight et Arn is a traditional herbal medicine, which has been used for centuries in southwest China in the treatment of cancer, neoplasia, and other diseases. The drug made from M. Tenacissima, named as antitumor injection, had been proved high clinical effective for hepatocellular carcinoma, lung cancer, and gastric cancer. Previous studies indicated that the main effective components in M. Tenacissima were C21 steroidals. The aim of the present work is the elaboration of constituents and the cytotoxic activities of C21 steroidals in the title herb. Twenty-four compounds were isolated and structurally determined from the ethanol extract under the bioassay-guided procedure, including sixteen C21 steroidals, three azulenes, four disaccharide derivatives, and a bisepoxyligan. There are twelve novel compounds among them. The cytotoxic activities of C21 steroidals were evaluated using MTT assays on three human non small cell lung cancer cells, NCI-H292, NCI-H460, and NCI-H1975 cell lines. Two C21 steroidals, TenacissosideIand Tenacigenin A, exhibited good potency against the three cell lines with IC50 values of 0.32 and 0.97, 0.74 and 2.69, 1.59 and 7.70µM, respectively.The results support the ethnomedicinal usage of M. Tenacissima. Acknowledgements: Thank the supporting grant for NCET-12 – 0578, 13 – 0624, 111Project B08044 and YLDX01013.

社区获得性肺炎（CAP）是指在医院外罹患的感染性肺实质炎症，包括具有明确潜伏期的病原体感染而在入院后潜伏期内发病的肺炎。CAP是威胁人类健康的一种常见感染性疾病，在成人和儿童中均有较高的发病率。据文献报道，CAP在普通成人中的年患病率为0.1％～1.16％，65岁以上人群的年患病率约为2.5％～4.4％；门诊患者中CAP的病死率为1％～5％，住院患者中平均为12％，ICU患者中为40％［1］。因此，对该病的治疗应给予足够的重视。

Background The chronic obstructive pulmonary disease assessment test (CAT) is an easy to use health-related quality of life questionnaire, the modified Medical Research Council (mMRC) dyspnea scale is a classic dyspnea scale which is widely used, while the correlation between them is still not clear. This study investigated the use of the Chinese translation of CAT in chronic obstructive pulmonary disease patients and its correlation with the mMRC dyspnea scale. Methods The multicenter cross-sectional study was conducted in 329 hospitals throughout China from March 1 to April 30, 2010. Chronic obstructive pulmonary disease patients completed both the assessment test and the dyspnea scale during a single study visit. Results Six thousand, four hundred and thirty-seven patients were evaluated; 74.9% were male and the mean age was (64.9±10.0) years. Median test scores in dyspnea grades 0 to 4 were 14, 16, 22, 26 and 32, respectively; these differences were statistically significant. The CAT score was moderately correlated with mMRC dyspnea grade ( r =0.579, P <0.001). There was no significant difference in mean CAT score between males and females, and patients of high and low socioeconomic status. Primary analysis suggested that CAT scores were higher in older patients (>65 years) than in younger patients (≤65 years) and increased with duration of formal education, but these findings were repudiated by further analysis of subgroups according to mMRC dyspnea grade. Conclusions There was no obvious confounding factor influencing use of the CAT in Chinese patients. CAT scores were moderately correlated with the mMRC dyspnea scale.

近年来提出,慢陛阻塞性肺疾病(COPD)是一种具有全身表现的炎症性疾病,特别在其严重阶段和急性加重期.南于炎症机制作用,COPD患者肺部炎性介质"溢出"进入血液循环,可引起重要的全身表现,如骨骼肌消耗、恶病质[1].全身炎症也可启动和恶化COPD合并疾病,如缺血性心肌病、心力衰竭、骨质疏松、正色素性贫血、肺癌、胃食管反流、临床焦虑和抑郁及糖尿病等.

CONTEXT:Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet. OBJECTIVES:To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice. MATERIALS AND METHODS:Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group. RESULTS:Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P > 0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P < 0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P < 0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P < 0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group. DISCUSSION AND CONCLUSIONS:These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.

OBJECTIVE:To explore the features of pulmonary interstitial pathological changes in diffuse interstitial lung disease (DILD) patients with positive anti-neutrophil cytoplasmic antibody (ANCA), and the similarities as well as differences between ANCA positive patients with non-primary vasculitis and primary systematic vasculitis.METHODS:Clinical data of 122 patients with DILD having ANCA examined from October 1995 to September 2008, were reviewed. Among the ANCA positive patients with non-primary vasculitis (Group A), those with primary systematic vasculitis (Group B), and the ANCA negative patients (Group C), the results of syndromes, signs, radiological manifestations, pulmonary function tests, bronchoscope examinations, bronchoalveolar lavage fluid (BALF) cytology and other laboratory examinations were compared.RESULTS:In the 122 DILD patients with ANCA results, 36 patients' ANCA (29.51%) were positive. The numbers of patients in Groups A, B, and C were 7, 29, and 86. Total lung capacity (TLC) decreased less and pleural pathological changes were more seen in Groups A and B than in Group C. Oliguria, haematuria, proteinuria, anaemia, and renal inadequacy in Group A, which were similar in Group C, appeared less than in Group B. Results of bronchoscope examination, BALF cytology, anti-nuclear antibody (ANA), and etc. were not significantly different among the three groups.CONCLUSION:In DILD patients, pulmonary interstitial changes of those with positive ANCA accompany with more pleural pathological changes and TLC decreased less than those with negative ANCA. In patients with positive ANCA, non-primary vasculitis had some similar clinical manifestations as primary systematic vasculitis, however, anaemia and renal damages were less seen in the non-primary vasculitis patients.

慢性阻塞性肺疾病(COPD)是一种以气流受限为特征的呈进行性发展的疾病,是对有害气体或有害颗粒的一种异常炎症反应.在有害物质刺激下,嗜中性粒细胞、肺泡巨嗜细胞聚集、活化,释放细胞因子、炎性介质,发生蛋白酶与抗蛋白酶失衡、氧化与抗氧化失衡是其主要发病机制.无疑这一理论是有根据的,已得到普遍认同.

病历摘要 患者男,54岁,因间断发热8个月、呼吸困难5个月,头痛、恶心、呕吐5 d,于2009年1月11日收入我院呼吸科病房,这是患者第4次入住我院,第3次入住我科病房.患2型糖尿病已10余年,个人史和家族史无特殊。

Objective To compare the performances of three foreign prediction rules with the severity criteria of the Chinese guidelines for CAP in identifying low-risk patients and evaluating severe pneumonia.Methods We retrospectively analyzed data from patients admitted with CAP to the respiratory department of Peking University Third Hospital from January of 2000 to April of 2007.Patients were stratified according to the Pneumonia Severity Index(PSI),CURB and CURB65 severity scores and the severity criteria of the Chinese guidelines.Furthermore,patients were classified into three risk groups(low,moderate and high)in the light of each rule.Distribution of patients,hospital mortality and intensive care unit(ICU)admission rate in each group of the predictive rules were analyzed.Sensitivity,specificity,positive predictive values,negative predictive values and the areas under the receiver operating characteristic curves(AUC)for predicting hospital mortality and ICU admission rate in each rule were compared too.Results In the light of PSI(class Ⅰ～Ⅲ),CURB(score 0)and CURB65(score 0~1),greater proportions of patients were classified as low-risk(73.9%,61.2% and 69.1%,respectively),while smaller proportions of patients were classed as moderate and high risk(20.0%,28.5%,21.8%;6.1%,10.3%,9.1%,respectively).Both low and moderate risk patients identified by these three rules had mortality(1.6%,2.0%,1.8%;9.1%,6.4%,8.3%,respectively).However,according to the severity criteria of the Chinese guidelines,smaller proportions of patients(7.3%)was identified as low-risk,while greater proportions of patients were defined as moderate and high risk(44.8%,47.9%),nevertheless,no death or ICU admission occurred in the low-risk group and ICU admission rate were 1.4% in moderate-risk group.The severity criteria of the Chinese guidelines had high sensitivity(100.0%,95.5%)and low specificity(55.5%,59.4%)for predicting hospital mortality and admission to ICU.On the contrary,The PSI Ⅴ,CURB score 2～4 and CURB65 score 3～5 all had high specificity but low sensitivity for the two outcomes.The severity criteria of the Chinese guidelines had a greater discriminatory power to predict mortality and admission to ICU(AUC:0.777,0.774).All these rules had low positive predictive values but high negative predictive values for the two outcomes.Conclusion The severity criteria of the Chinese guidelines and three foreign prediction rules have different strengths and weaknesses as prediction tools.Further research to identify better prediction tools is required.

子鼠与年新,腊梅贺岁寒,团坐话秋池,寄语悬壶事。2008年1月,戊子年前夕,来自呼吸内科和医院药学的专家会聚一堂,共叙呼吸系统疾病治疗药物的进展与合理应用,包括医院获得性肺炎、肺动脉高压、基因组学与个体化给药、咳嗽的辨证选药等。会议由北京大学第三医院赵鸣武教授主持,解放军总医院第一附属医院崔德健教授,中国医学科学院北京协和医院陆慰萱教授,海军总医院孙忠实主任,北京大学积水潭医院张石革主任分别就上述4个课题相继发言,回顾进展,阐述合理用药原则,并与参会专家切磋互动,促成纪要如下,与医药学界同仁共勉。

COPD是一个严重的健康问题.WHO预测到2020年COPD将成为全球第5大疾病负担和第3大死亡原因[1].目前COPD被认为是一种多因素构成的疾病,包括肺脏内外结构和功能的改变[2],炎症在疾病发病进展过程中起着核心作用[3-4].

Objective To investigate the significance of interleukin-17(IL-17)antibodies in cigarette smoke-induced chronic obstructive pulmonary disease(COPD)in mice.Methods Male C57/BL6 mice were randomly divided into COPD group(n=8),COPD+anti-IL-17 Ab group(n=8),and normal control group (n=10).The Rumher of cells in bronchoalveolar lavage fluid(BALF)was calculated and the concentrations of IL-17 in lung tissues was measured by enzyme-linked immunosorbent assay.Histoiogic analysis of the lungs was done in each group.Results The intra-airway pressure(IP),peak expiratory flow(PEF),and Ip slope in anti-IL-17 Ab group were insignificant compared with those of COPD group.The total cell count in BALF was significantly higher in COPD group than in normal control group(P＜0.01).Compared with COPD group.the total cell count in COPD+anti-IL-17 Ab group was decreased[(19.64±1.89)×104/ml and(15.47±2.99)×104/ml(P＜0.01)],neutrophils in BALF were obviously decreased,(22.98±8.46)%,(8.58±6.77)%(P＜0.01).The airway inflammation was alleviated in COPD+anti-IL-17 Ab group by histologic analysis.The concentration of IL-17 in lung tissue was significantly lower in COPD+anti-IL-17 Ab group [(0.084±0.041)pg/mg Pro] than in the COPD group[(0.221±0.081)pg/mg pro](P＜0.01).Conclusions IL-17 might play a role in airway neutrophilic inflammation in cigarette smoke-induced COPD in mice.Anti-IL-17 could decrease the Rumbet of neutrophils in the BALF and attenuate the neutrophilic airway inflammation.

Objective To analyze the airflow obstruction of sarcoidosis patients and the influencing factors.Methods Clinical data of 31 patients with sarcoidosis from April 1989 to September 2007 were reviewed.Among the patients with normal pulmonary function test(PFT),(Group A),airflow obstruction(Group B) and non-obstructive abnormal PFT(Group C),the results of PFT,radiological manifestations,bronchoscope examination,bronchoalveolar lavage fluid(BALF) cytology and serum angiotensin converting enzyme(ACEI) level were compared.Results Compared to Group A and C,FEV1% and small airway function parameters of patients of Group B were decreased significantly.Reticular-nodular-fibrotic pattern was more commonly found in the lung CT of Group B and C than that in Group A.Results of bronchoscope examination;BALF cytology and ACEI level were not significantly different among the three groups.Conclusions Patients with sarcoidosis might be with obstructive airflow,and structural changes of small airway resulting from its pathological processes as well as of surrounding pulmonary tissue might have close relationship with airflow obstruction.

OBJECTIVE To investigate the changing patterns and associated factors of microbial pathogens which caused ventilator-associated pneumonia (VAP) in our respiratory intensive care unit (RICU) from 1995 to 2004. METHODS Cases of VAP in our RICU from 1995 to 2004 (n = 137) were retrospectively analyzed, 47 cases from 1995 to 1999 and 90 cases from 2000 to 2004. VAP was diagnosed according to the following criteria: pneumonia occurred 48 hours after tracheal intubations; new or progressive infiltrative opacities on chest X ray film; and at least two of the following clinical features: (1) Temperature > 38.0 degrees C or < 35.5 degrees C, (2) WBC > 10 x 10(9)/L or < 4 x 10(9)/L, (3) purulent airway secretions; and positive bacterial cultures (the samples obtained through endotracheal intubations). The data were analyzed using statistical software SPSS version 11.5. Continuous data were expressed as (-x) +/- s. t-test and chi(2)-test were used for continuous and categorical data, respectively. Logistic regression analysis was used to determine the risk factors for special pathogens. RESULTS The mean incidence of VAP was 17.9% from 1995 to 2004 (137/765), 16.2% from 1995 to 1999 (n = 47, 3.1% - 29.8%) and 19.6% from 2000 to 2004 (n = 90, 12.4% - 27.7%). From 1995 to 1999, common pathogens were Stenotrophomonas maltophilia (n = 15, 23.4%), Pseudomonas aeruginosa (n = 12, 18.8%), Aerobacter cloacae (n = 8, 12.5%) and Acinetobacter baumanii (n = 7, 10.9%). From 2000 to 2004, common pathogens were Acinetobacter baumanii (n = 40, 34.2%), Pseudomonas aeruginosa (n = 32, 27.4%), Staphylococcus aureus (n = 24, 20.5%) and Stenotrophomonas maltophilia (n = 8, 6.8%). There were 2 cases (2/64, 3.1%) caused by Staphylococcus aureus from 1995 to 1999, and both were caused by Methicillin-resistant Staphylococcus aureus (MRSA); there were 24 cases caused by Staphylococcus aureus from 2000 to 2004, and 21 cases (21/117, 17.9%) were caused by MRSA.There were 11 (11/47, 23.4%) and 45 (45/90, 50.0%) cases with central intravenous catheters in the period of 1995 to 1999 and 2000 to 2004, respectively. In the period of 1995 to 1999 and 2000 to 2004, durations of aerosolized therapy were (46 +/- 55) and (28 +/- 30) days. There were 12 patients (12/47, 25.5%) using second-generation cephalosporin before VAP occurred in the period of 1995 to 1999 and 7 patients (7/90, 7.8%) in the period of 2000 to 2004. There were 13 patients (13/47, 27.7%) using penicillin before VAP in the period of 1995 to 1999 and 10 patients (10/90, 11.1%) in the period of 2000 to 2004. There were 10 patients (10/47, 21.3%) using quinolones before VAP in the period of 1995 to 1999 and 46 patients (46/90, 51.1%)in the period of 2000 to 2004. The occurrence of Staphylococcus aureus VAP may be related to the cross-infection between inpatients (Wald = 16.690, P < 0.01, OR = 9.212). VAP caused by Stenotrophomonas maltophilia was positively related to duration of aerosolized therapy (Wald = 7.852, P < 0.01, OR = 1.021). VAP caused by Acinetobacter baumanii was positively related to third-generation cephalosporin usage (Wald = 5.553, P < 0.05, OR = 3.461). CONCLUSIONS The incidence of VAP was not increased in the recent 10 years in our RICU, but the incidence of VAP caused by Acinetobacter baumanii. Staphylococcus aureus and MRSA increased significantly, may be related to the decrease of duration of aerosolized therapy, the usage of different kinds of antibiotics and cross-infection between inpatients.

Objective. Previous studies have demonstrated that exercise-induced asthma and bronchial hyperresponsiveness commonly occur in athletes. The present study investigates pulmonary function and cytokine levels in professional athletes to explore the impact of various sports on respiratory system function and to evaluate the possible role of systemic anaphylaxis. Methods. Lung function was measured at rest in professional athletes without a history of smoking. Athletes were recruited from 10 different sports including swimming, water ballet, shooting, volleyball, softball, football, kickboxing, fencing, judo, and track and field. Measurements included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), vital capacity (VC), peak expiratory flow (PEF), maximal mid-expiratory flow curve (MMEF), and forced expiratory flow rate (FEF25-75%). In addition, the medical history of all athletes was recorded. Correlations between lung function measurements and the different sports, age, gender, height and weight were analyzed. In some athletes, serum was sampled to detect IL-4 and IL-10 concentrations. In these subjects, the correlation between pulmonary function and cytokine levels was analyzed. Results. A total of 147 professional athletes and 30 healthy volunteers were enrolled in the study. Allergic rhinitis and asthma were detected only in swimmers with an incidence of 56.52% (13/23) and 8.70% (2/23), respectively. Lung function measures were significantly correlated with sport, age, gender, height, and weight. Ventilation functions (including FVC, FEV1, FEV1/FVC, and MMV) in male athletes were superior to those in females, and the ventilation functions in swimmers were superior to those in others. However, the small airway functions (MMEF, FEF50, FEF75) in swimmers and in track and field athletes were lower than predicted (swimmers: 72%, 70%, and 78%, respectively; track and field athletes: 79%, 75%, and 99%, respectively). Serum analyses for IL-4 and IL-10 revealed that IL-4 concentrations were higher in swimmers 69.34 +/- 22.4 pg/mL relative to non-swimmers (p = 0.000). By contrast IL-10 concentrations were lower in swimmers 34.94 +/- 9.71 pg/mL than that in the static group (44.69 +/- 16.32 pg/mL; p = 0.027). IL-4 levels were negatively correlated with FEV1%, FEF25%, FEF50%, and MMEF%. By contrast, IL-10 levels were not correlated with any of these measures. Conclusions. The lung function measurements were correlated with sport, age, gender, height, and weight in the various athletes. The lung capacity of swimmers was greater than that of other athletes. Small airway dysfunction was observed in some swimmers and endurance athletes. We observed an association between systemic anaphylaxis and small airway dysfunction after prolonged regular training, particularly following swimming and endurance training.

Objective: Guidelines on oxygenation policies and on the prevention and treatment of retinopathy of prematurity (ROP) were issued by the Chinese Medical Association in 2004. This study was undertaken to determine the incidence of and risk factors for ROP among preterm infants in Beijing, the capital of China, after implementation of the guidelines.Methods: Neonates with birth weights (BW) <= 2000 g or gestational age (GA) <= 34 weeks admitted to the six largest neonatal intensive care units in Beijing during 2005 were enrolled. Ophthalmological examinations started 3-4 weeks after birth, and ROP was classified using the revised International Classification. Maternal and perinatal risk factors for type 1 ROP were analysed.Results: Retinopathy of prematurity was detected in 10.8% of 639 neonates who had complete eye examinations, 23 of whom (3.6%) developed type 1 ROP and were treated. The rate of ROP needing treatment has not declined since 2002. Logistic regression analysis indicated that low BW, apnoea >20 s, anaemia, hypoxic-ischaemic encephalopathy and placenta abruption were significantly associated with type 1 ROP.Conclusion: In Beijing, rates of ROP needing treatment are high, and affected babies are more mature than in NICUs in high-income countries. More needs to be done to prevent ROP through improved neonatal care.

目的:了解中国优秀运动员肺功能水平并探讨长期不同运动训练对呼吸系统的影响.方法:2004年6月～11月,对10个不同项目运动队147名运动员进行肺通气功能测试,包括最大分钟肺通气量(MMV)、用力肺活量(FVC)、用力呼气一秒量(FEV1)、用力呼气一秒率(FEV1/FVC)、呼气峰流速(PEF)、用力呼气流速(FEF)和最大中段呼气流速(MMF),分析不同项目运动训练对运动员肺功能的影响.结果:各项目运动员FVC、FEV1/FVC有显著性差异(P＜0.05).游泳、球类、力量项目运动员FVC及FEV1优于其他项目,游泳项目运动员FVC/BMI及FEV1/BMI最高.各项目运动员小气道功能实测值有显著性差异(P＜0.05);游泳项目运动员MMF、FEF50和FEF75实测值均低于其他类型运动员,其实测值/预计值分别为72%、70%、78%;耐力项目运动员MMF、FEF50和FEF75实测值/预计值也低于正常,分别为79%、75%和99%.结论:不同项目运动员肺功能之间存在差异;游泳运动员肺功能高于其他类型运动员;部分长期从事游泳和耐力训练运动的运动员存在小气道功能受损.

Objective: To observe lung function changes and pathological changes of airway lung tissues in rats with different passive-smoking durations,and,so as to obtain some useful information about establishment of animal models of chronic obstructive pulmonary disease(COPD).Methods: 36 male rats were randomly divided into 4 groups: passive-smoking for 4 weeks(group 4w),6 weeks(group 6w),and 10 weeks(group 10w) and group that did not receive passive-smoking(control group,group CT).Lung function and pathological changes of airway-pulmonary tissues in all rats were measured.Results: Peak expiratory flow (PEF) and intra-airway pressure slope(Ip slope) were significantly higher in group 6w and group 10w than in group CT(P0.01 or P0.05).The rates of airflow-limitation were higher in group 10w(100%) and group 6w(62.5%) than in group 4w(0)(all P0.01).Phenomena of airway-tissue thickening,airway narrowness,emphysema,airway wall infiltration of inflammatory cells,caliciform cell metaplasia,airway-wall necrosis,and hyperplasy of fibrous connective tissue and smooth muscle were more obvious in group 10w than in group CT(P0.01 or P0.05).In group 6w,5 of 8 rats had emphysematous characteristics and airway stenosis.And the degrees of inflammatory cell infiltration,caliciform cell metaplasia,airway-wall necrosis,hyperplasy of fibrous connective tissue and smooth muscle in this group were also higher than those in group CT(P0.01 or P0.05).PEF were passively correlated with hyperplasy of fibrous connective tissue and smooth muscle respectively in group 6w and group 10w.However,rats in group 4w hadn't any emphysematous changes or airway stenosis.Conclusions: The formation of COPD model is associated with the amount of cigarette smoking and the length of smoking time.Within certain range,the longer the smoking time is,the more obvious the pathological changes of airway-pulmonary tissues are,and the higher the rate of airflow limitation is as well.