吸烟校正因素间接调整法在职业流行病学队列研究中的应用

目的介绍一种新的吸烟校正因素间接调整法在职业流行病学队列研究中的应用。方法以1981—1999年香港男性矽肺回顾性队列研究人群纯石英暴露组作为研究实例,用吸烟组[1/((1-PAR%)×RR)]与非吸烟组(1/(1-PAR%))各自的吸烟校正因素校正原始的标准化死亡比(SMR),用暴露超相对危险度和增效指数作为指标来判断吸烟与暴露对肺癌死亡的危险有无偏离乘法和相加模型。结果非吸烟和吸烟组矽肺队列人群的吸烟校正因素分别为1/0.33和1/1.62,校正吸烟后矽肺队列肺癌的SMR由原来的1.61(95%CI:1.22～2.10)显著地下降到1.08(95%CI:0.81～1.41),结果与Axelson方法完全一致。矽肺超相对危险度和增效指数分别为0.63(95%CI:0.08～0.79)和0.90(95%CI:0.42～1.94),提示吸烟与矽肺对肺癌死亡的危险呈明显的负相乘交互作用。结论吸烟校正因素间接调整法的优势是能定量分析和评估吸烟的混杂和交互作用的影响,但也有局限性。     

不同类型厂矿接尘工人肺癌病因学研究──矽尘或矽肺与肺癌的关系

为评价游离二氧化硅（简称矽尘或ＳｉＯ２）是否致肺癌？矽肺是否是肺癌前变基础？选择四类接尘厂矿进行队列和队列内病例对照研究。队列对象６８２８５人。有矽肺６４８７例，肺癌３３０例（男３１９，女１１），配对照１３５８例。根据厂矿历年工业卫生记录和近期对已知致癌物监测结果，定量评估了每个对象的接尘水平及每个病例对照的累积接触量。研究对象追访到１９８９年底，死亡６１９２人。与全国居民死亡平均数计算的期望值近似。全死因中癌症是第一死因，但全癌低于国家居民死亡率。分析结果说明：（１）矽尘单独存在时不是肺致癌剂。肺癌不超高，与接尘关系不明显；（２）在６４８７名矽肺队列中，肺癌相对危险度仅比非矽肺高０．２２倍，主要反应在铜铁矿工人中（Ｒ＝２．２），而矽肺患病率最严重的钨矿工人，其肺癌危险度反而随接尘水平上升而下降，再则肺癌死亡率与矽肺期别不呈正比；形态学上观察也不支持肺癌病变与矽肺纤维化病变相关。本研究结果难以支持矽尘或矽肺与肺癌病因学相关的假说。     

景德镇瓷厂工人死因分析

目的 探索危害陶瓷工人健康的主要疾患及职业有害因素对工人寿命的影响.方法 采用流行病学队列研究方法,对景德镇3个瓷厂1972年到1974年在册且工作一年以上所有陶瓷工人建立队列,随访至2003年底.队列中对死者均查询死因,陶工尘肺由当地疾病控制中心诊断小组确诊,肺癌均收集医院诊断病例.以全国城市居民年龄别死亡率为参照计算标化死亡比(SMR).结果 队列成员共4957名,随访至2003年底,共计130 783.6人年,死亡1636人,死亡率为1250.9/10万,累计死亡率为33.1%.影响陶瓷工人寿命的主要疾病按累计死亡率从高到低排序分别是:恶性肿瘤、心血管疾病、呼吸系统疾病、传染性疾病.与全国平均水平比较,陶瓷工人全死因死亡率基本持平,标化死亡比为1.01,死亡率明显升高的疾病有呼吸系统疾病(SMR=1.30)、陶工尘肺(SMR=36.35)、传染性疾病(SMR=5.08)和肺结核(SMR=4.06).陶瓷粉尘对工人寿命的影响十分明显,接尘工人多种疾病的死亡率均高于非接尘组,除陶工尘肺外,接尘组肺癌(RR=1.9,95%CI:1.2～3.1)、呼吸系统疾病(RR=2.4,95%CI:1.8～3.2)、肺结核(RR=1.6,95%CI:1.2～2.1)明显高于非接尘组,差异有统计学意义.研究还发现全死因、肠癌、肺癌、呼吸系统疾病、肺结核危险度均随接尘严重程度而明显增加,呈现接触一反应关系.结论 陶瓷行业主要职业危害为粉尘,卫生工作重点应是控尘和预防肺结核.     

接尘、吸烟者死亡危险度比较的前瞻性队列研究

目的 比较接尘、吸烟对死亡的影响。方法 以1989～1992年广州市实施并建立的职工职业健康监护档案为基础资料，选年龄≥30岁的80987名接尘和无接尘职工为研究对象，进行前瞻性队列研究。结果 (1)队列平均43．5岁，主要为工人、中学文化程度、已婚，接尘率16．3％，吸烟率43．7％，饮酒率335%。(2)队列平均随访8年，失访35人，死亡1539人，以恶性肿瘤死亡为主。(3)调整相关混杂因素后，全死因、恶性肿瘤、心脑血管疾病等死亡相对危险度(RR)，接尘者和吸烟者基本一致，但鼻咽癌、呼吸系统疾病死亡RR值，接尘者高于吸烟者，而肺癌、胃癌死亡RR值，吸烟者分别是接尘者的2．2倍和1．5倍；接尘可协同吸烟致死亡危险性明显增加。(4)男性总死因、恶性肿瘤和呼吸系统疾病死亡RR值，矽尘接触者高于吸烟者，心脑血管疾病死亡RR值，木尘接触者也高于吸烟者。(5)人群死亡归因危险度百分比(PARP)吸烟者是接尘者的2．5倍。(6)男吸烟者全死因、恶性肿瘤、肺癌、胃癌的死亡危险随日吸烟量、烟龄的增加而明显递增，冠心病、呼吸系统疾病的死亡危险则分别随日吸烟量、烟龄的增加而增加。结论 接尘、吸烟者死亡RR值基本一致，接尘与吸烟存在协同作用，某些死因死亡危险吸烟者较明显，某些接尘者较明显；吸烟者PARP较接尘者高；吸烟与死亡危险存在明显的剂量效应关系。     

某焦化厂职工癌症死因的调查分析

目的研究焦化厂职业有害因素对癌症死亡的影响.为预防癌症,保护工人健康提供依据.方法采用队列与队列内病例对照研究相结合的方法.计算主要死因的标化死亡比(SMR),相对危险度(RRMH)和绝对危险度(OR).结果观察人群24 923人年,从1975～1995年21年间癌症死亡59人,其中肺癌21人,占第一位死因.炼焦工人的肺癌显著超高,SMR＝4.17,P＜0.01.并随着接触工龄的延长,RRMH呈递增趋势.病例对照研究表明,肺癌与焦炉逸散物之间有显著性关联;与吸烟和呼吸系统疾病史亦有显著性关联.白血病与苯溶物之间没有关联.其它癌未见有意义的结果.结论接触焦炉逸散物与炼焦工人肺癌发生有关,重度吸烟和呼吸系统疾病史与肺癌发生也有关.     

矽尘、矽肺与肺癌关系的Meta分析

目的对矽尘暴露、矽肺与肺癌间的关系进行综合评价，为制定科学的防制措施提供依据。方法本文收集了1997年以来关于矽尘、矽肺与肺癌关系的原始文献，按纳入与排除标准分类整理，采用Meta分析，分别分析矽尘、矽肺与肺癌间的关系，并进行敏感性分析。结果分别综合所选资料，得出各自合并后的标化死亡比（SMR）值及95％的可信区间（CI），分别为SMR矽尘=1．30（CI：1、07～1.57，P=0．007），SMR矽肺=1.65（CI：1．21～2．25，P=0．002），矽尘暴露和矽肺与肺癌间的关联均有统计学意义。结论本文显示矽尘对人类有微弱致癌作用，矽肺与肺癌有中度关联，但最终定论还需深入研究。     

金属矿尘接触与肺癌发病的危险度定量评价

本文对大厂矿长坡锡矿1960～1974年井下接尘的工人进行了一次回顾性定群研究。研究队列共1113人,贡献人年26780。观察期间死于肺癌45人,与全国、上海人口比较,SMR分别为2184和519。以累计接尘量作定量评价的结果表明,工人吸入的矿尘与肺癌发病呈明显的剂量—反应关系。用对数线性模型拟合接尘量与吸烟量对肺癌发病的作用,发现接尘量与吸烟量同时引入模型后拟合优度最佳。控制吸烟因素后,不同累计接尘量水平对肺癌发病的相对危险度逐次为4.18、5.20、13.01、16.07;控制接尘量后,不同吸烟量的相对危险度分别为1.74、4.19,接尘量与吸烟量及肺癌发病危险度都呈现剂量—反应关系,表明接尘和吸烟同时为肺癌发病的危险因子。     

滑石粉尘对陶瓷工人的健康效应

目的：探讨滑石粉尘对陶瓷工人呼吸系统疾病发生发展的影响。方法：采用历史前瞻性队列研究，全体队列成员按是否接触矽尘和滑石尘分为不接尘组，矽尘组和滑石尘矽尘组，运用优势比（Odds Ratios,OR)方法作计算分析。结果：滑石尘矽尘组工人的非恶性呼吸道疾病（如尘肺）和肺心病的死亡危险度与矽尘组类似，但其癌症的死亡危险度，特别是肺癌死亡比不接尘组明显超高，OR＝4．73，P＜0．01）。结论：认为颗粒型滑石可能是瓷厂工人中致肺癌因子，滑石粉尘对矽肺发病也有明显的促进作用。     

某矿井下接尘,矽肺,吸烟与肺癌发病关系的研究

为了评价井下接尘、矽肺、吸烟与肺癌发病的关系,在大厂锡矿职工人群中进行了一次肺癌的病例-对照研究。结果发现,职工肺癌发病主要与井下接尘和吸烟有关。非条件Logistic回归模型的多因素分析表明,矽肺与增加肺癌发病的危险度无显著性意义,接尘与吸烟之间也无效应修饰作用。     

吸烟与矽肺：某矿区的定群研究

通过对1077名井下矿工队列的28年回顾性定群研究,发现吸烟组矽肺发病率为13.02%,非吸烟组为6.85%。吸烟组矽肺的标化发病率比为171.43(95%CI=144.69～203.97)。以接尘工龄作时间变量,用Weibull回归模型分析累积接尘量和吸烟对矽肺的影响。结果表明在平衡了接尘工龄后,累积接尘量和吸烟对矽肺发病的影响有显著性意义,说明了有吸烟习惯的接尘工人发生矽肺的危险度比不吸烟者大。因此,在预防矽肺的措施上,应强调控制吸烟的重要性。     

Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up

OBJECTIVES—To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997.METHODS—Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society''s criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates.RESULTS—The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox''s proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates.CONCLUSIONS—The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors—such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines—rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.     

Lung cancer mortality among a cohort of men in a silicotic register

To examine any association between silicosis and lung cancer, the clinic records of a cohort of 1502 silicotic workers diagnosed after 1981 were reviewed. All of the essential data, including occupational exposure, smoking habits, radiographic extent of silicosis, and vital status of each subject, were noted. The standardized mortality ratio for various causes of death was calculated. Thirty-three patients died from lung cancer, giving a standardized mortality ratio of 1.94 (95% confidence interval, 1.35 to 2.70). However, smoking accounted for most of the excess of lung cancer deaths among the silicotic workers in the cohort, and no consistent relationship between lung cancer mortality risk and either duration of exposure to silica dust or severity of silicosis was observed. There is no conclusive evidence in our data to support the hypothesis that lung cancer may be associated with silicosis.     

Mortality from lung cancer among Sardinian patients with silicosis

The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the association between silicosis and lung cancer. Among them, attention should be given to chronic airways obstruction as an independent risk factor for lung cancer in patients with silicosis.     

Mortality from lung cancer among Sardinian patients with silicosis.

The mortality of 724 subjects with silicosis, first diagnosed in 1964-70 in the Sardinia region of Italy, was followed up through to 31 December 1987. Smoking, occupational history, chest x ray films, and data on lung function were available from clinical records for each member of the cohort. The overall cohort accounted for 10,956.5 person-years. The standardised mortality ratios (SMRs) for selected causes of death (International Classification of Diseases (ICD) eighth revision) were based on the age specific regional death rates for each calendar year. An excess of deaths for all causes (SMR = 1.40) was found, mainly due to chronic obstructive lung disease, silicosis, and tuberculosis with an upward trend of the SMR with increasing severity of the International Labour Office (ILO) radiological categories. Twenty two subjects died from lung cancer (SMR = 1.29, 95% confidence interval (95% CI) = 0.8-2.0). The risk increased after a 10 and 15 year latency but the SMR never reached statistical significance. No correlation was found between lung cancer and severity of the radiological category, the type of silica (coal or metalliferous mines, quarries etc), or the degree of exposure to silica dust. A significant excess of deaths from lung cancer was found among heavy smokers (SMR = 4.11) and subjects with airflow obstruction (SMR = 2.83). A nested case-control study was planned to investigate whether the association between lung cancer and airway obstruction was due to confounding by smoking. No association was found with the ILO categories of silicosis or the estimated cumulative exposure to silica. The risk estimate for lung cancer by airflow obstruction after adjusting by cigarette consumption was 2.86 for a mild impairment and 7.23 for a severe obstruction. The results do not show any clear association between exposure to silica, severity of silicosis, and mortality from lung cancer. Other environmental or individual factors may act as confounders in the association between silicosis and lung cancer. Among them, attention should be given to chronic airways obstruction as an independent risk factor for lung cancer in patients with silicosis.     

Mortality of a cohort of men in a silicosis register: further evidence of an association with lung cancer

Lung cancer mortality from 1980 to 1986 was studied in a cohort of 1,419 men in a silicosis register who had no previous exposure to asbestos and polyaromatic hydrocarbons. The 28 deaths from lung cancer were statistically in excess of expected (SMR 2.03; 95% CI 1.35-2.93). Excess risks of lung cancer were found in both underground workers (SMR 3.41; 95% CI 1.10-7.97; based on 5 deaths) and surface workers (SMR 1.87, 95% CI 1.18-2.81; based on 23 deaths). All lung cancer deaths were smokers. There was an increase in SMRs with longer latency periods and years of exposure, with the greatest risk found in those who had worked for 30 or more years after more than 30 years since first exposed (SMR 3.07, based on 16 deaths). The risk for lung cancer was higher in those with tuberculosis (SMR 2.52; 95% CI 1.52-3.94) and showed an increasing trend with severity of silicosis, from category 1 to 3 and from category A to C, with highest risk in those with tuberculosis and category 3 (SMR 4.44 based on 3 deaths) or tuberculosis and category C (SMR 7.63 based on 7 deaths). Most of the excess lung cancer risk in silicotics is due to smoking, but a synergistic effect between smoking and silica/silicosis on the risk of lung cancer is also likely. In particular, a possible role of silicosis and tuberculosis as the fibrotic seedbed for malignant growth in the lung is strongly supported.     

Respiratory cancer and other chronic disease mortality among silicotics in california

Silicotics have increased mortality from tuberculosis (TB) and from nonmalignant respiratory diseases (NMRD), including silicosis and silicotuberculosis. Since the publication of the International Agency for Research on Cancer monograph in 1987 indicating that silica was a probable human carcinogen, there has been an extensive debate about the cancer risks among silicotics. The authors identified 590 claims for silicosis among a registry of lung diseases compiled from California Workers' Compensation cases from 1945 to 1975. Using state vital records, we determined the mortality risks from 1946 to 1991. Our findings confirmed that these claimants had a significantly elevated risk for all causes of death with a standardized mortality ratio (SMR) of 1.30 (95% confidence interval [CI] = 1.18, 1.43); TB had a SMR of 56.35 (95% CI = 41.10, 75.40) and NMRD a SMR of 3.80 (95% CI = 3.11, 4.60). Cancers of the trachea, bronchus, and lung had a SMR of 1.90 (95% CI = 1.35, 2.60). For malignancies of the large intestine, there was a previously unreported SMR of 2.08 (95% CI = 1.14, 3.50). Mortality from all diseases of the heart was significantly less than expected with a SMR of 0.68 (95% CI = 0.55, 0.83); cancers of the prostate and lymphatic system were also significantly low with SMRs of 0.26 (95% CI = 0.03, 0.94) and 0.17 (95% CI = 0.04, 0.97), respectively. Workers with silicosis should be warned about these chronic disease risks, and prevention efforts to control occupational silica dust exposure should become a higher priority.     

Silicosis and smoking strongly increase lung cancer risk in silica-exposed workers

It remains controversial whether silica is a human lung carcinogen. In this study, we estimated the relative risks of lung cancer due to silica and silicosis by meta-analysis. We collected papers published from 1966-2001 which epidemiologically reported on the relationship between silica/silicosis and lung cancer. We removed papers which did not exclude the effects of asbestos and radioactive materials including radon. We selected the most recent one if some papers were based on the same cohort. Based on the selected papers, we summarized the lung cancer risks from silica, silicosis and non-silicosis with exposure to silica, by meta-analysis using a random effects model. The pooled relative risks were 1.32 (95% confidence interval (CI), 1.23-1.41) for silica, 2.37 (95% CI, 1.98-2.84) for silicosis and 0.96 (95% CI, 0.81-1.15) for non-silicosis with exposure to silica. Since some papers on silica did not exclude silicosis, the risk due to silica itself may be smaller than 1.32. It was less possible that silica exposure directly increases lung cancer risk. On the other hand, the relative risk, 2.37 for silicosis suggested that silicosis increases lung cancer risk. Meta-analysis also revealed that cigarette smoking strongly increased the lung cancer risk in silicotic patients (relative risk, 4.47; 95% CI, 3.17-6.30). Thus, the present study suggested the great importance of preventing silicosis and smoking cessation in reducing lung cancer incidence in silica-exposed workers.     

Exposures to silica mixed dust and cohort mortality study in tin mines: exposure-response analysis and risk assessment of lung cancer

BACKGROUND: Mineral dusts that contain crystalline silica have been associated directly or indirectly with the development of pneumoconiosis or silicosis, non-malignant respiratory diseases, lung cancer, and other diseases. The health impacts on workers with silica mixed dust exposure in tin mines and dose-response relationships between cumulative dust exposure and the mortality from lung cancer are investigated. METHODS: A cohort of 7,837 workers registered in the employment records in 4 Chinese tin mines between 1972 and 1974 was identified for this study and the mortality follow-up was traced through 1994. Of the cohort, the cause of death was ascertained for 1,061 (97%) of the 1,094 deceased workers. Standardized mortality ratios (SMRs) were calculated for all workers, non-exposed workers, and dust-exposed workers with different exposure levels, silicotics, and non-silicotics based on Chinese national rates. RESULTS: The mortality from all causes in four tin mines was nearly the same as the national mortality. Malignant neoplasm, cerebrovascular disease, and cardiovascular disease accounted for 68.6% of all deaths. Mortality excess from lung cancer, liver cancer, all malignant diseases, and non-malignant respiratory diseases was observed among dust-exposed workers; a 50-fold excess of pneumoconiosis was observed. There was an upward trend for SMRs of lung cancer was noted from no exposure to low, medium, and high exposure levels (SMRs=1.29, 2.65, 2.66, 3.33). The shape of the exposure-response curve for risk of lung cancer at high exposure levels was inconsistent in these four mines. CONCLUSIONS: The findings indicated a positive dose-response relation between exposure to cumulative dust and the mortality of lung cancer. High arsenic content in dust particles, together with crystalline silica, may play an important role in causing increased mortality from lung cancer.