铁矿接尘工人尘肺发病及死因的队列研究

发布时间：2018-04-05 05:07

本文选题：队列研究　切入点：尘肺　出处：《华中科技大学》2012年博士论文

【摘要】：尘肺是由于长期接触生产性粉尘引起的以肺组织纤维化为主要病理特征的疾病,是我国以及很多其他发展中国家发病最多、危害最严重的职业病。卫生部发布的年度职业病报告显示,2010年我国报告新发职业病27240例,其中尘肺病23812例,占总数的87.42%。2009年和2010年,我国报告的新发尘肺病例分别比前一年上升了33.85%和64.28%,并且群体性病例报告不断出现,严重影响社会和谐和经济的可持续发展,因此,防治尘肺是我国职业病防治的重中之重。生产性粉尘存在于很多行业,如矿山开采,公路桥梁建设、陶瓷生产等。其中矿山开采是生产性粉尘危害最严重的行业之一,在生产过程中的诸多环节如风钻、爆破、采矿、破碎、运输等产生的生产性粉尘浓度都很高。矿工长期吸入生产性粉尘可以引起肺泡炎症,肺间质增生,胶原沉积,最终发展为以纤维化为主要病理表现的尘肺病。既往研究显示,在累积粉尘暴露量和粉尘中游离二氧化硅含量接近的情况下,不同工人的尘肺发病情况不尽相同,提示尘肺的发生不仅与接触生产性粉尘有关,还受到其他因素如吸烟、患其他呼吸系统疾病、遗传易感性等的影响。本课题组前期研究时,选择湖北某大型国有铁矿1960年1月1日到1974年12月31日之间登记在册,并且在该铁矿工作过一年以上的所有工人建立了研究队列。1986年以前为回顾性资料收集,1986年以后为前瞻性随访,本研究在前期研究的基础上继续随访队列人群到2011年底。本研究目的是分析该铁矿尘肺发病规律及其影响因素,以期为铁矿及类似行业尘肺防治工作提供参考依据。同时,收集了死亡队列成员的死亡相关信息,分析生产性粉尘接触对从业工人疾病死亡率的影响,为促进工人健康,减少死亡提供指导。本研究共包括三部分：第一部分铁矿接尘工人尘肺发病规律及其影响因素研究在前期研究的基础上,本研究随访铁矿队列人群至2011年底,完成了95.93%的队列成员的终身职业史随访。尘肺病例均由具有资质的职业病诊断机构进行确诊。同时,通过铁矿历年各工作岗位粉尘浓度监测资料建立了工种-年代-总粉尘浓度矩阵,结合个人的职业史计算每个队列成员的累积粉尘接触量(cumulative dust exposure,CDE),分析铁矿接尘工人尘肺的发病规律和影响因素。本研究队列共7666人,男性6543人,女性1123人,到2011年底,共随访332609.88人年。其中接尘工人3658人,共随访150216.02人年,诊断尘肺328例,人年发病率0.22%。78.05%的尘肺发病年龄在40-60岁之间。 50年代建矿之初主要接尘工作点的平均总粉尘浓度超过11mg/m3,合格率只有33%左右。随着生产工艺的改进和防尘降尘措施的采用,铁矿的总粉尘浓度迅速下降,2000年以来平均1.92 mg/m3(1.54 mg/m3-2.47 mg/m3),合格率达到90%以上。不同年代开始接尘的工人接尘量和尘肺发病有显著差异。1960年之前开始接尘的1818名工人平均累积接尘量为95.41±56.68 mg/m3-y,其中有285人被诊断为尘肺,占该铁矿诊断尘肺病例总数的86.89%；1970年之后开始接尘的865名工人的平均累积接尘量为45.51±22.84 mg/m3-y,有11人被诊断为尘肺。该铁矿尘肺的平均潜伏期为22.68年(6.92年-50.92年),其中71.34%的病例在10-30年之间。尘肺的发病危险性随着接尘量的增大而升高,呈现剂量反应关系,按累积接尘量将接尘工人分为高接尘组(CDE≥100 mg/m3-y)、中接尘组(50mg/m3-y≤CDE＜100mg/m3-y)和低接尘组(CDE50 mg/m3-y)后,高、中、低接尘组的尘肺累积发病率分别为22.26%、7.32%和2.92%。调整性别、吸烟、患肺结核等因素之后,高、中接尘组相对于低接尘组的危险度分别为4.83(95%CI：3.97-7.76)和2.18(95%CI：1.36-3.39)。校正接尘量、性别等因素后,接尘工人中吸烟者尘肺发病危险度是不吸烟者的1.74倍(p0.01),患有结核的接尘工人尘肺发病危险度是未患结核者的12.78倍(p0.01)。本部分研究结果表明,尘肺的发病危险随着累积接尘量的增加而升高,吸烟和患肺结核等也会增加尘肺发病危险度。第二部分铁矿尘肺发病与遗传易感性的关联研究显示,接尘情况类似的工人,尘肺发病存在很大差异,说明尘肺发病可能受到遗传易感性的影响。矽尘进入机体后被肺泡巨噬细胞识别和吞噬,引起活性氧(Reactive oxygen species, ROS),自由基的产生和释放,溶酶体裂解,促进Nalp3炎性体的形成和成熟,从而促进细胞凋亡蛋白酶1 (Caspase-1)的活化,活化的Caspase-1可以刺激前炎性因子如白细胞介素(interleukin, IL)-1β等前体的分化成熟,从而促进纤维化的发生发展。研究对象包括铁矿的182名尘肺病例、214名非尘肺接尘工人和180名不接尘工人。由经过培训的调查人员对研究对象进行问卷调查,并在空腹时采集外周静脉血5m1,肝素抗凝,用于提取基因组DNA。采用TaqMan技术测定在生产性粉尘的免疫识别和诱发炎性反应中具有重要作用的Nalp3-Caspase-1-IL-1β通路上选定的五个SNP位点的基因型,采用Logistic多元回归分析基因型与铁矿尘肺发病之间的关联。本研究得到同济医学院伦理道德委员会批准。调整出生年月、性别、吸烟和接尘情况等因素后,Nalp3基因SNP位点rs34298345G/-型接尘工人相对于G/G型工人的尘肺发病危险度是2.96(95%CI：1.39-6.28)；Caspase-1基因SNP位点rs1042743 G/A型接尘工人相对于G/G型工人的尘肺发病危险度是3.61(95%CI：1.60-8.13)。Nalp3基因SNP位点rs1539019以及IL-1β基因SNP位点rs1143627和rs1143634突变频率与尘肺发病危险呈现负相关趋势,但差异没有统计学意义(p0.05)。本部分研究表明rs34298345和rs1042743位点的突变型可能增加尘肺发病危险性,应该加强对这类工人的健康监护,减少尘肺发生。第三部分铁矿接尘工人死因分析本课题组对铁矿接尘工人队列进行了长达43.07年的随访,通过职工医院病历等收集了队列中死者的详细死亡资料,分析接尘对接尘工人死因的影响。根据累积粉尘接触量将接尘工人分成高、中、低接尘组,通过计算相对危险度(relative risk, RR)比较不同接尘量工人死因的差异,同时以全国城市居民年龄别疾病别死亡率为参考,计算主要疾病的标化死亡比(standardized mortality rates, SMRs)及其95%可信区间。铁矿共有接尘工人3658人,共随访150216.02人年,死亡1581人,累积死亡率43.22%,人年死亡率为1052.48/10万人年。铁矿接尘工人的前6位主要死因依次为恶性肿瘤、呼吸系统疾病、心血管疾病、脑血管疾病、意外事故和消化系统疾病。高、中、低接尘组的全死因累积死亡率依次为57.12%、43.92%和33.97%。调整性别,开始工作年龄,吸烟情况等因素后,高接尘组和中接尘组相对于低接尘组的死亡危险度分别为2.07(95%CI：1.69-2.55)和1.32(95%CI：1.11-1.56)。全死因、恶性肿瘤及其中的肺癌、心血管疾病、脑血管疾病、呼吸系统疾病及其中的COPD和尘肺的死亡率均随着接尘量的增加而升高,呈现剂量反应关系。诊断的328名尘肺病人中有248人死亡,累积死亡率75.61%,明显高于非尘肺接尘工人的40.03%。尘肺病人的肺癌、呼吸系统疾病和心血管疾病的死亡率分别为非尘肺接尘工人的2.01、4.81和1.49倍,差异有统计学意义(p0.05)。与同期全国城市居民的平均水平相比,铁矿接尘工人死亡率升高的有全死因、肺癌、心血管疾病、脑血管疾病、呼吸系统疾病、尘肺和意外事故。本部分研究显示铁矿接尘工人的死亡率高于全国城市居民的平均水平,并且与接尘呈现剂量-反应关系。尘肺病人的死亡率高于非尘肺接尘工人。综上所述,铁矿尘肺的发病率随着接尘量的增加而升高,同时也受到吸烟、肺结核、基因多态性等的影响。加强对生产性粉尘的控制,不仅可以减少尘肺的发生,也可以降低与粉尘接触相关的疾病死亡率。
[Abstract]:According to the annual occupational disease report released by the Ministry of Health , there are 27240 new cases of occupational disease reported in China in 2010 . Among them , there are 2,812 cases of new occupational diseases reported in China in 2010 , accounting for 87.42 % of the total . In 2009 and 2010 , the new cases reported in China increased by 33.85 % and 64.28 % respectively compared with the previous year .
Production dust exists in many industries , such as mine exploitation , highway bridge construction , ceramic production , etc . Among them , mining is one of the most serious industries in productive dust .
Previous studies have shown that in cases where the cumulative dust exposure and the free silicon dioxide content in the dust are close to each other , the occurrence of dust - lungs of different workers is different , suggesting that the occurrence of dust - lungs is not only related to the contact with the production dust , but also affected by other factors such as smoking , other respiratory diseases , genetic susceptibility , and the like .
In the preliminary study of the study group , a large state - owned iron mine in Hubei was selected to register between January 1 , 1960 and December 31 , 1974 , and all workers who had worked for more than one year in the iron mine set up a study cohort . In 1986 , a retrospective data collection was conducted , followed by a prospective follow - up in 1986 , and the study was followed up on the basis of previous studies to follow up the cohort population until the end of 2011 .
The purpose of this study is to analyze the pathogenesis and influencing factors of dust - dust in the iron mine , with a view to providing a reference for the prevention and treatment of dust and lung in iron ore and similar industries . At the same time , the related information of death queue members is collected , and the influence of the contact on the mortality of workers in the industry is analyzed , which provides guidance for promoting the health of workers and reducing death . The study consists of three parts :
Study on the pathogenesis and influencing factors of dust - dust in the first part of iron ore dust - collecting workers
At the end of 2011 , the follow - up iron ore cohort population of this study completed 95.93 % of the cohort member ' s lifetime career history follow - up . All cases of dust and lung were diagnosed by qualified occupational disease diagnosis organizations . Meanwhile , the cumulative dust exposure ( CDE ) of each cohort member was calculated based on the monitoring data of dust concentration in each post of iron mine . The cumulative dust exposure ( CDE ) of each cohort member was calculated based on the occupational history of the individual .
The study cohort was 7666 , male 6543 , female 1123 , by the end of 2011 , a total of 3,2609 . 88 persons were followed up . Among them , 3658 workers were followed up for a total of 150216.02 person years .
The average total dust concentration of the main dust collecting working point in the early 1950s was more than 11mg / m3 and the qualification rate was only about 33 % . With the improvement of the production process and the dust reduction measures , the total dust concentration of iron ore decreased rapidly , the qualified rate reached over 90 % .
The average cumulative exposure of 865 workers who began to dust after 1970 was 45.51 卤 22.84 mg / m3 - y , and 11 were diagnosed with dust . The average latency of the dust - dust was 22.68 years ( 6.92 years - 50.92 years ) , among which 71.34 % were between 10 - 30 years .
The morbidity risk of dust - dust increased with the increase of dust - collecting volume . The incidence of dust - dust accumulation was 22.26 % , 7.32 % and 2.92 % in high , middle and low dust groups . The risk of dust - dust group was 4.83 ( 95 % CI : 3.97 - 7.76 ) and 2.18 ( 95 % CI : 1.36 - 3.39 ) respectively .
After correction of dust and sex , the risk of dust - lung disease among dust - exposed workers was 1.74 times that of non - smokers ( p0.01 ) , and the risk of dust - lung disease of dust - collecting workers with tuberculosis was 12.78 times ( p0.01 ) .
The results of this study showed that the risk of dust - dust increased with the increase of cumulative dust exposure , smoking and pulmonary tuberculosis .
Correlation between the pathogenesis and genetic susceptibility of the second part of iron - iron mine
The study shows that there is a great difference in the morbidity of dust and lungs similar to those of workers exposed to dust . It is suggested that the pathogenesis of dust may be influenced by genetic susceptibility . After entering the organism , the generation and release of reactive oxygen species ( ROS ) , free radicals production and release , lysosomal lysis , activation of Caspase - 1 can stimulate the differentiation and maturation of pro - inflammatory factors such as interleukin ( IL ) - 1尾 , and thus promote the development of fibrosis .
Two hundred and eighty - one hundred and eighty - two dust - free workers and 180 non - dust workers were investigated . The subjects were investigated by trained investigators , and peripheral venous blood ( 5m1 ) and heparin ( anticoagulant ) were collected from the trained investigators to extract genomic DNA .
After adjusting the factors such as birth date , sex , smoking and dust exposure , the risk of dust - lung morbidity among the SNP loci rs34298345G / - type workers exposed to G / G workers was 2.96 ( 95 % CI : 1.39 - 6.28 ) .
The risk of dust - lung morbidity of the SNP site rs1042743 G / A of the Caspase - 1 gene was 3.61 ( 95 % CI : 1.60 - 8.13 ) compared with the G / G workers . rs1143627 and rs1143634 SNP loci rs1143627 and rs1143634 were negatively correlated with the risk of dust and lung disease , but the difference was not statistically significant ( p . 05 ) .
This partial study shows that the mutation of rs34298345 and rs1042743 sites may increase the risk of dust and lung disease , and should strengthen the health monitoring of these workers and reduce the occurrence of dust .
Analysis on the Cause of Death of Dust - Connected Workers in the Third Part of Iron Mine
The study group conducted a follow - up of 43.07 years for iron ore dust collection workers ' queue , collected the detailed death data of the dead in the queue through the medical records of the staff and staff , and analyzed the effect of the death cause of the dust and dust collecting workers .
According to the cumulative dust exposure , the dust - collecting workers were divided into high , middle and low dust - collecting groups , and the relative risk ( RR ) was calculated to compare the causes of death among workers with different dust exposure . At the same time , the standardized mortality rates ( SMRs ) and their 95 % confidence intervals were calculated by calculating relative risk ( RR ) .
The total annual mortality rate was 43.22 % , the cumulative mortality rate was 43.22 % , and the annual mortality rate was 1052.48 / 100000 person years . The first six main causes of death were malignant tumor , respiratory system disease , cardiovascular disease , cerebrovascular disease , accident and digestive system disease .
The total death rate of the high , middle and low dust groups was 57.12 % , 43.92 % and 33.97 % , respectively . After adjusting sex , starting work age and smoking status , the risk of death in high dust collecting group and middle dust collecting group was 2.07 ( 95 % CI : 1.69 - 2.55 ) and 1.32 ( 95 % CI : 1.11 - 1.56 ) , respectively . All cause of death , malignant tumor and its lung cancer , cardiovascular disease , cerebrovascular disease , respiratory system disease and its mortality all increased with the increase of dust exposure , showing dose response relationship .
Of the 328 patients diagnosed , 248 died and the cumulative mortality rate was 75.61 % , which was significantly higher than that of non - dust - exposed workers ( 40.03 % ) . The mortality rates of lung cancer , respiratory diseases and cardiovascular diseases were 2.01 , 4.81 and 1.49 times of the non - dust - free workers , respectively , and the difference was statistically significant ( p . 05 ) .
Compared with the average of the urban residents in the same period , the death rate of the iron ore - connected workers increased , including all causes of death , lung cancer , cardiovascular diseases , cerebrovascular diseases , respiratory diseases , dust and lung and accidents .
The study shows that the mortality rate of dust - connected workers is higher than the average of urban residents in the whole country , and the dose - response relationship is related to the exposure to dust . The mortality rate of patients with dust - lung disease is higher than that of non - dust - exposed workers .
To sum up , the incidence of dust - dust in iron ore is increased with the increase of dust collecting , and it is affected by smoking , pulmonary tuberculosis , gene polymorphism and so on . The control of productive dust can not only reduce the occurrence of dust , but also reduce the mortality associated with dust exposure .

【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R135.2

【相似文献】