Development of a chronic inhalation reference level for respirable crystalline silica

Chronic inhalation exposure of workers to crystalline silica can result in silicosis. The general public can also be exposed to lower levels of crystalline silica from quarries, sand blasting, and entrained fines particles from surface soil. We have derived an inhalation chronic reference exposure level for silica, a level below which no adverse effects due to prolonged exposure would be expected in the general public. Incidence of silicosis and silica exposure data from a cohort of 2235 white South African gold miners yielded a reference level of 3 microg/m3) for respirable silica (particle size as defined occupationally) using a benchmark concentration approach. Data from cohorts of American gold miners, Chinese tin miners, diatomaceous earth workers, and black South African gold miners yielded similar results with a range of 3-10 microg/m3. Strengths of the chronic reference exposure level include the availability of several large long-term studies of inhalation in workers at varying exposure concentrations, adequate histopathological and radiologic analysis, adequate follow-up of exposed workers, a dose-response effect in several studies, observation of a No Observed Adverse Effect Level in the key study, and the power of the key study to detect a small effect. Uncertainties include the general underestimation of silicosis by radiography alone and the uncertainties in exposure estimation.     

矽肺患者周围血淋巴细胞亚群、TNF-α、sIL-2R水平分析

【摘要】目的分析不同期别矽肺患者周围血淋巴细胞亚群和肿瘤坏死因子（TNF-仅）、血清可溶性白细胞介素_2受体（sIL-2R）的变化,探讨不同期别矽肺患者免疫水平的差异。方法应用直接免疫荧光-流式细胞技术检测86例矽肺患者（I期32例、Ⅱ期30例、Ⅲ期24例）周围血淋巴细胞亚群,同时应用酶联免疫吸附法（ELISA）检测血清中TNF．d和sIL-2R的水平,与30例正常健康人作比较。结果周围血CD3、CIM比例和CD4／CD8水平矽肺患者组低于正常人组（P〈0．05）,随着矽肺期别的升高,CD3、CD4比例和CD4／CD8下降,但无统计学差异（P〉0．05）;各期矽肺患者周围血TNF-α、sIL-2R的水平高于正常对照组（P〈O．05）,随着矽肺期别的升高,sIL-2R明显升高（P〈0．05）,TNF-α明显下降（P〈0．05）。结论矽肺患者周围血细胞免疫功能低下,TNF-α和sIL-2R协同参与矽肺发生和发展过程。     

硅沉着病患者胸部CT分析

目的对硅沉着病患者胸部CT影像学表现进行描述,为临床诊断硅沉着病提供参考。方法以鞍山市职业病防治院收治的32例硅沉着病患者的胸部CT为研究样本,对现有的影像资料进行回顾性分析,探讨硅沉着病的特点。结果胸部CT可清晰显示硅沉着病患者肺部矽结节的形态和密度、肺纹理、肺气肿以及肺门、纵隔淋巴结的改变。结论胸部CT对于硅沉着病患者的诊断具有重要价值。     

长沙市花岗岩石材加工业矽肺流行病学调查

目的探讨花岗岩石材加工业矽肺的发病现状和规律,预测流行趋势,为制定防治对策提供科学依据。方法采用回顾性调查方法,制定调查方案,收集长沙市自1963年1月—2010年12月该行业所有矽肺病例资料,建立数据库,用SPSS17.0进行统计分析。结果 47年来,长沙市该行业新发矽肺病118例,其中Ⅰ期矽肺78例(66.10%),Ⅱ期矽肺35例(29.66%),Ⅲ期矽肺5例(4.24%)。好发工种为石工(81.51%)、凿岩工(9.24%)、运输工(1.68%)、其他工种(7.56%)。平均发病工龄约为34 a,平均发病年龄约为55岁。结论该市花岗石矽肺病新发病例1960—1980年呈逐渐增长趋势,1990年后病例明显减少。2000年后未出现新发病例。需加大粉尘危害监测与风险控制,建立粉尘暴露人群健康监护机制。     

矽肺动物模型的病理观察

目的 探讨二氧化硅致大鼠及贵州小香猪肺组织纤维化的变化.方法 采用非暴露法建立SD大鼠、贵州小香猪矽肺动物模型,光学显微镜及透视电镜下观察其肺内病理变化,免疫组化法观察肺组织中细胞因子的表达.结果 (1)大鼠及猪矽肺模型主要形态学变化:染尘7～15d,在肺泡腔内可见矽尘、大量的巨噬细胞、尘细胞、肺上皮细胞及少量的中性粒白细胞,形成巨噬细胞肺泡炎及Ⅰ级结节;染尘30～90 d,肺组织的呼吸性细支气管及肺泡内、小叶间隔、血管及支气管周围、胸膜下形成Ⅰ～Ⅲ级结节,少数动物模型可见Ⅳ级结节,伴淋巴细胞浸润.(2)大鼠及贵州小香猪肺组织中细胞角蛋白(CK)、肺表面活性物质相关蛋白A( SP-A)、吞噬细胞(CD68)、碱性成纤维细胞因子(b-FGF)、肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、转化生长因子(TGF-1)、NF-κB/P50、NF-κB/P65、血管内皮生长因子(VEGF),随着染尘时间的延长,表达逐渐减弱,但仍高于对照组.60～90 d CD68仍呈阳性表达.(3)电镜观察肺泡上皮和巨噬细胞的变化:在SiO2刺激下,肺泡Ⅰ型上皮脱落,Ⅱ型上皮细胞及巨噬细胞增生,且细胞功能活跃.结论 建立的大鼠及猪肺纤维化模型符合巨噬细胞肺泡炎至纤维化的演变过程.     

白细胞介素-4基因多态性与矽肺易感性的病例对照研究

目的 探讨白细胞介素-4(IL-4)(-33、+45、VNTR、+429、+448)位点基因多态性与矽肺易感性的关系.方法 采用整群病例对照研究,病例组为101名Ⅰ期矽肺患者,对照组为与病例年龄相近、同性别、同民族、同一工作地点、累积接尘工龄相近的非矽肺接尘工人121名.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测IL-4的5个基因位点的基因型并进行分析.结果 两组对象的年龄、累积接尘工龄、吸烟率比较,差异均无统计学意义(P＞0.05).IL-4(+429)位点仅存在GA 基因型,未发现GG和AA基因型;IL-4(+448)位点仅存在CC基因型,未发现CG和GG基因型.病例组IL-4(+45)位点AA、GG和AG基因型频率分别为55.4%、10.9%和33.7%,与对照组(62.0%、11.6%、26.4%)比较,差异无统计学意义(x2=1.386,P＞0.05);病例组IL-4(VNTR)位点B1B1、B282和B182基因型频率分别为73.3%、1.0%和25.7%,与对照组(68.6%、1.7%、29.8%)比较,差异无统计学意义(x2=0.580,P＞0.05);病例组IL-4(-33)位点TY、CC和CT基因型频率分别为55.4%、11.9%和32.7%,与对照组(69.4%、4.1%、26.4%)比较,差异有统计学意义(x2=6.751,P＜0.05).结论 未发现IL-4(+45、VNTR)与矽肺患病的关系,未发现IL-4(+448、+429)存在多态性现象.IL-4(-33)位点多态性与矽肺患病有关,携带IL-4-33等位基因C的接尘者患矽肺的危险性增加.

Abstract：

Objective To explore the relationship between polymorphisms of interleukin-4 (IL-4)gene (-33,+45,VNTR,+429,+448) and the susceptibility of silicosis. Methods In a case-control study, the case group consisted of 101 patients with silicosis, and was matched with the control group (121 workers without silicosis), according to the age, sex, nationality, working place, exposure to dust. The polymorphisms of IL-4(five locus) detected by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. Results There was no difference of age, exposure and smoking between case group and control group (P＞0.05). The two groups had good comparability. Only the GA genotype in the IL-4 (+429)locus was found, the genotypes of AA and GG were not found. The CC genotype in the IL-4 (+448) locus was found, the genotypes of CG and GG were not found. The frequencies of AA, GG and AG of IL-4 (+45) locus in the case and control groups were 55.4%, 10.9%, 33.7% and 62.0%, 11.6%, 26.4%, respectively, there was no the significant difference between case and control groups (P＞0.05). The frequencies of B1B1, B2B2 and B1B2of IL-4 (VNTR) locus in the case and control groups were 73.3%, 1.0%, 25.7% and 68.6%, 1.7%, 29.8%,respectively, there was no the significant difference between case and control groups (P＞0.05). The frequencies of TT, CC and CT in IL-4 -33 locus in the case group were 55.4%, 11.9% and 32.7%, which were significantly higher than those (69.4%, 4.1%, 26.4%) in control group (P＜0.05). Conclusions There was no relationship between IL-4 (+45,VNTR) genotypes and prevalence of silicosis in this study. The polymorphisms of IL-4(+448)site were not found which may be related to the race. The relationship between genetic polymorphism of IL-4(-33) locus and silicosis development was found, Workers with IL-4(-33) allele C are susceptible to the silica.     

矽肺患者氧化应激指标及外周血单核细胞NF-κB水平的变化

目的 观察矽肺患者氧化应激指标及外周血单核细胞NF-κB水平的变化,探讨矽肺发生发展的机制.方法 选择某铸造厂接触矽尘作业工龄在1年以上的工人200例为接尘组,该厂2008年住院及门诊随访的矽肺患者130例为矽肺组,32例0+病例为观察对象组,同时选择某酒店服务人员100例为对照组.分别测定超氧化物歧化酶(SOD)、血清中谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮合酶(NOS)活力,一氧化氮(NO)、丙二醛(MDA)含量及总抗氧化能力(T-AOC),外周血单核细胞核蛋白中NF-κB水平.结果 与对照组比较,接尘组和矽肺组NO含量明显升高,SOD活力明显降低,差异均有统计学意义(P＜0.01).与对照组及接尘组比较,矽肺组T-AOC水平、NOS活力、MDA含量均明显升高,差异均有统计学意义(P＜0.01).与对照组[(223.360±46.838)U/ml]比较,接尘组及矽肺组GSH-Px活力[(231.164±36.484)、(270.469±39.228)U/ml]明显升高,且矽肺组GSH-Px活力明显高于接尘组,差异均有统计学意义(P＜0.05,P＜0.01).与观察对象组[(256.906±21.418)U/ml]和Ⅰ期矽肺组[(259.594±34.790)U/ml]比较,Ⅲ期矽肺组GSH-Px活力[(290.750±39.129)U/ml]明显升高,差异均有统计学意义(P＜0.05).与对照组[(59.71±9.27)ng/L]比较,接尘组及矽肺组NF-κB水平[(72.06±9.12)、(85.25±11.64)ng/L]明显升高,且矽肺组NF-κB水平明显高于接尘组,差异均有统计学意义(P＜0.01).血清中GSH-Px活力与矽肺分期呈正相关(r=0.507,P＜0.01).外周血单核细胞核蛋白NF-κB水平与矽肺分期、年龄、GSH-Px活力、NO含量呈正相关,差异均有统计学意义(r值分别为0.376、0.243、0.233、0.221,P＜0.01).结论 机体氧化和抗氧化系统的失衡与矽肺的发生发展有关,并与NF-κB的活化一致.

Abstract：

Objective To investigate the change of indicators of oxidative stress in serum and NF-κB in peripheral blood mononuclear cells of patients with silicosis, and explore the mechanism of the development of silicosis. Methods The subjects were divided into (1) 200 workers exposed to SiO2 for at least 1 years in a foundry served as the dust-exposure group; (2) 130 cases with silicosis (Ⅰ phase silicosis 64 cases, Ⅱ phase 46 cases Ⅲ phase 20 cases) served as the silicosis goup; (3) 32 cases with 0+ phase silicosis in the foundry served as the observed group,(4)100 subjects from a hotel served as the control group. The serum including superoxide dismutase (SOD), nitric oxide (NO), serum glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), nitric oxide synthase (NOS), lipid malondialdehyde (MDA) and NF-κB protein levels in peripheral blood mononuclear cells were determined, respectively. Results Compared with the control group,NO levels in dust-exposed group and silicosis group significantly increased, and SOD decreased significantly (P＜0.05 or P＜0.01). Compared with the control group and dust-exposed group, T-AOC, NOS, MDA levels in silicosis group significantly increased (P＜0.05 or P＜0.01). GSH-Px in dust-exposed group and silicosis group were (231.164±36.484) and (270.469±39.228)U/md, respectively which were significantly than that [(223.360±46.838) U/ml] in control group (P＜0.05 or P＜0.01), and there was significant difference of GSHPx between the silicosis group and the dust-exposed group significantly (P＜0.01). GSH-Px level [(290.750±39.129) U/ml] in Ⅲ phase silicosis group were significantly higher than those [(256.906±21.41) and (259.594±34.79) U/ml] in observation group and Ⅰ phase silicosis group (P＜0.05). NF-κB levels [(72.06±9.12) and (85.25±11.64) ng/L] in dust-exposed group and silicosis group were significantly higher than that [(59.71±9.27) ng/L] in control group (P＜0.01), and there was significant difference of between the silicosis group and the dust-exposed group (P＜0.01). There was a positive correlation between serum GSH-Px level and the silicosis stages (r=0.507,P＜0.0l). Also there was a positive correlation between NF-κB level and silicosis stages, age, GSH-Px or NO levels (r=0.376, 0.243, 0.233, 0.221, P＜0.01). Conclusion The imbalance of oxidative and anti-oxidation system and the activation of NF-κB are related with the occurrence and development of silicosis. The monitoring of oxidative stress indicators and NF-κB is beneficial to the prediction and prognosis assessment of silicosis.     

矽肺病危害的严重性与可防性

矽肺病是我国发病最多、危害最严重的职业病,至今无特殊治疗药物,一旦患病,受累终生。从我国,我省近几年治理矽尘危害的经验来看,矽肺病是完全可以预防的。但为何从总体来看,我国矽肺发病率仍没有得到有效控制呢？主要有如下几个方面：执行力度不够;企业经营管理者对矽尘危害认识的滞后;职工自身对矽尘危害认识不够;职业卫生工作近年来出现“重治轻防”“重研轻防”的误导现象。要控制、消除矽肺病发生,建议尽快解决好以下     

矽肺CT影像学表现特征分析

目的研究矽肺的CT影像学表现特征。方法对我院呼吸内科的70例矽肺患者的影像资料进行回顾性分析,比较采用低剂量和常规剂量作为扫描条件的CT特征结果,并观察矽肺在CT扫描结果中的影像学特征。结果采用低剂量和常规剂量扫描影像统计结果(阴影大小、密集度和分期)比较差异不具有统计学意义(P0.05);70例患者均存在肺实质纤维斑块:II期(14例)和Ⅲ期(24例)患者;间质纤维化:50例患者存在,Ⅱ期和Ⅲ期共有9例患者出现纤维状密度增加和血管束变粗,Ⅲ期中有6例患者出现了典型的小叶间隔增厚和胸膜厚度增加;Ⅱ期(8例)和Ⅲ期(9例)患者存在肺气肿;肺门和纵膈淋巴结:Ⅰ期(4例)存在明显的矽粉沉着伴肿大,Ⅱ期(6例)和Ⅲ期(12例)存在典型的斑点状钙化;Ⅱ期(7例)和IⅢ期(16例)存在典型胸膜厚度增加。结论矽肺在CT扫描中的影像特征结合患者生活情况可做出明确诊断;低剂量CT可作为矽肺患者筛查疾病的辅助检查。     

2010～2011年广西新诊断尘肺病发病特征分析

目的 探讨广西尘肺病发病特点,为有效防控尘肺病提出相关对策.方法 对广西2010～2011年新诊断503例尘肺病例的临床资料以及工种、行业、地理分布等资料进行分析.结果 广西2010 ～2011年新诊断尘肺病503例,其中一期尘肺388例(77.14％)、二期尘肺80例(15.90％)、三期尘肺35例(6.96％);其中矽肺450例(89.46％).接尘工龄≤15年新尘肺病例占75.55％;一期尘肺病接尘工龄为(12.37±10.21)年.新发尘肺病主要集中于中小型企业和私营企业,共占新发尘肺病的68.79％.河池、南宁为新发尘肺病与矽肺病例发生的主要城市,共占新诊断尘肺病例和矽肺病例的74.16％和76.22％;有色金属矿采业为新发尘肺病和矽肺病病例分布的主要行业,分别占新诊断尘肺病例和矽肺病例的65.21％和71.33％;新发尘肺病主要发生于粉尘危害较严重的粉(破)碎工和凿岩工等采矿工种,占统计工种的89.86％.结论 广西尘肺病仍然处于高发趋势,需加强对开展有色金属矿山开采业的中小企业特别是私营企业尘肺病防治,同时加强对务工人员的尘肺病防治知识宣传、职业健康检查和对高危地区、高危行业、高危工种的执法监督.