职业性哮喘

近年来 ,职业性哮喘的发病率有逐渐增高的趋势 ,而职业性致哮喘物的种类也不断增多 ,其引起职业性哮喘的机制主要有变应性机制、药理性机制和神经源性机制。对哮喘者进行职业性病因判断需要依靠病史、肺功能实验、最大呼气流速 (PEF)的监测、免疫学试验、抗原特异性支气管激发试验 (A -BPT)、生物标准物等指标综合分析。职业性哮喘大多预后不佳。     

职业性哮喘患者肺功能变化的临床观察

目的了解职业性哮喘患者的肺功能变化特点。方法对15例职业性哮喘患者行支气管现场激发试验时的肺功能参数进行分析,并同时记录发生时间及患者症状、体征。结果①发作期和激发前肺功能值比较,大部分肺功能参数差异有统计学意义(P0.05)。发作期用力肺活量(FVC)、第1秒用力呼气容量(FEV1)、最大用力呼气流速(PEF)、最大呼气中段流速(MMEF)、25%和50%肺活量时的最大呼气流速(FEF25、FEF50)显著低于激发前;②经直线相关分析,FEV1与FVC下降率之间,FEF50与MMEF下降率之间以及FEV1与MMEF下降率之间均呈直线相关(rs=0.825,P=0.006;rs=0.992,P=0.000;rs=0.881,P=0.004)。③激发后60 min内现场支气管激发试验阳性10例,且全部出现全身发汗、颜面发绀及肺部哮鸣音等严重临床表现,占67%;激发2 h后的现场支气管激发试验阳性5例,占33%。结论职业性变应原致使患者的大小气道功能受限,职业性哮喘可呈速发相反应或迟发相反应。呈速发相反应患者的临床表现明显。     

职业性哮喘的^99mTcDTPA吸入动态显像观察

观察６例可疑职业性哮喘患者，于抗原支气管激发试验前、后进行９９ｍ锝二正三胺五乙酸（９９ｍＴｃＤＴＰＡ）气溶胶吸入动态显像，并与肺功能、抗原皮试、抗原特异性ＩｇＥ、ＩｇＧ４等对比观察。结果显示激发前显像呈现放射性均匀一致，其支气管／肺放射性比值（Ｒ）平均为１．１４±０．１７。而激发后，肺功能ＦＥＶ１值分别下降１９．７％～６５．２％，全部呈阳性反应；其Ｒ值则增加２．１１～１８．５不等；显像呈现不同程度的放射性中心性沉积或外周稀疏，其程度与临床症状、体征、肺功能下降情况相平行。该方法可直接观测患者对特殊抗原物的气道反应性及气道阻塞范围、分布、程度等，能更客观地对职业性哮喘进行病因评价。     

职业性哮喘的综合评价

对４３例可疑与职业有关的哮喘住院病例，进行了职业史、病史、物理检查，结合变应原支气管激发试验（Ａ－ＢＰＴ）、变应原皮试（ＳＴ）、特异性ＩｇＥ（Ｓ－ＩｇＥ）及特异性ＩｇＧ４（Ｓ－ＩｇＧ４）等项检查。结果表明：Ａ－ＢＰＴ阳性率６７．４％，阳性组的ＳＴ、Ｓ－ＩｇＥ、Ｓ－ＩｇＧ４阳性率分别为５３．０％，５４．５％和５９．０％，明显高于激发阴性组。ＳＴ、Ｓ－ｌｇＥ、Ｓ－ＩｇＧ４与Ａ－ＢＰＴ的符合率分别为７１．０％，６９．４％及７３．９％，Ｓ－ＩｇＥ与Ｓ－ｌｇＧ４符合率为７８．３％。以上指标在评价职业病因方面具有明显的特异性与敏感性，几项指标的综合分析，则能极大地提高病因诊断的正确性与阳性率。     

作业现场支气管激发试验在职业性哮喘诊断中的应用体会

作业现场支气管激发试验可以确认支气管哮喘是否由于职业接触致喘物所致。通过对2例职业性哮喘患者的诊断,认识到在诊断中通过现场职业卫生学调查可以确认作业场所是否存在职业性致喘物,通过作业现场支气管激发试验可以确认支气管哮喘是否由职业接触致喘物所致。因此,职业性哮喘诊断中满足病因的确认和疾病的诊断,既要良好地把握诊断标准,又要灵活运用诊断方法,在科学诊断的同时,也要避免对患者的再次伤害,保护劳动者健康。     

邻苯二甲酸酐哮喘大鼠模型的制备及实验免疫学观察

目的进一步研究苯酐哮喘的发病机制，建立苯酐哮喘大鼠模型并观察其体内抗原特异性ＩｇＧ和ＩｇＥ的变化。方法苯酐致敏大鼠抗原攻击后描记呼吸曲线以监测气道反应，酶联免疫吸附试验及被动皮肤致敏试验检测抗原特异性ＩｇＧ和ＩｇＥ。结果苯酐可引起大鼠气道高反应性和体内抗原特异性ＩｇＧ和ＩｇＥ水平升高。结论苯酐哮喘属半抗原致敏变应性哮喘。该实验所建模型可用于苯酐哮喘发病机制的进一步研究     

甲苯二异氰酸甲酯所致支气管哮喘患者的支气管激发试验及免疫学研究

对18例临床上诊断为支气管哮喘的TDI作业者进行变应原BPT,并与其它免疫学指标对比观察。发现BPT阳性14例(占77.8％),其中速发反应7例,迟缓反应6例,双相反应1例。BPT阳性者的肺功能指标FVC、FEV_1、MMF、PF、V_(75)、V_(50)、V_(25)等均有明显降低。免疫指标中以IgA、特异性IgE的增高为著,各占7例及9例,并与BPT阳性反应相一致。以上证明了TDI哮喘的变态反应机理,特别是与IgE介导的速发型反应有关。此外,BPT作为一种病因诊断手段,有明显的特异性及实用性。     

职业型支气管激发试验诊断TDI职业性哮喘一例报告

职业型支气管激发试验诊断ＴＤＩ职业性哮喘一例报告北京市劳动卫生职业病防治研究所（朝外东大桥北，１０００２０）袁忠孝，洪屹ＴＤＩ，又名二异氰酸甲苯酯，用于制造聚氨酯树脂及其它泡沫塑料，是常见的化学致敏物。本文报道通过职业型支气管激发试验确诊为ＴＤＩ职业...     

邻苯二甲酸酐哮喘动物模型的被动皮肤过敏试验

对８份邻苯二甲酸酐（ＰＡ）致敏豚鼠血清进行被动皮肤过敏（ＰＣＡ）试验及ＰＣＡ抑制试验，证实血清中存在ＰＡ特异性ＩｇＥ及ＩｇＧ型抗体。通过宫内被动致敏观察也可证实胎鼠体内存在ＰＡ特异性抗体。这种ＰＡ特异性抗体的存在与ＰＡ嘟喘的生成机制的密切关系。     

乙二胺所致哮喘的临床免疫学研究

对5例EDA哮喘患者做了非特异性支气管激发试验,结果气道反应性轻度增高2例,中度增高3例。8例EDA哮喘患者做了特异性支气管激发试验,结果全部阳性,其中7例为迟发相反应,1例为双相反应。而普通哮喘组和正常对照组激发试验全部阴性。激发试验前后测定了总补体、组胺,作了嗜酸细胞计数。激发后EDA哮喘组嗜酸细胞明显增加,并有统计学意义(P<0.05),与普通哮喘组和正常对照组激发后嗜酸细胞计数比有显著差异(P<0.01)。EDA哮喘组激发后组胺释放增加(P<0.05)。EDA哮喘组总补体均未见有意义的改变。EDA-BSA皮内试验结果表明,EDA哮喘4例为阳性,普通哮喘组1例为阳性,而对照组无1例阳性。EDA-BSA作抗原,以酶联免疲分析证明了EDA哮喘组有3例有特异性IgG抗体,而其他两组未发现特异性IgG抗体,EDA哮喘组未检出特异性IgE抗体。     

邻苯二甲酸酐哮喘实验动物模型制备及病理学观察

45只体重250—300克的豚鼠用邻苯二甲酸酐—牛血清白蛋白注射免疫,15只正常豚鼠作对照。吸入邻苯二甲酸酐—人血清白蛋白后,实验组有40只动物(88%)出现哮喘发作。用其中4只哮喘动物血清给正常未致敏豚鼠做被动转移试验,亦同样诱发致哮喘。哮喘动物的病理学观察表现为支气管壁的嗜酸性粒细胞浸润,管腔中有由嗜酸性粒细胞、粘液及少许脱落的上皮细胞组成的栓塞,肺泡腔扩大,肺泡壁变薄等一系列符合一般变应性哮喘的形态学改变。     

二苯甲烷二异氰酸酯哮喘患者的气道反应性与免疫学研究

10例MDI哮喘病人进行了支气管组胺激发试验(BHPT),4例阳性,6例阴性,后者有4例已脱离MDI工作1～3年;对照人员BHPT全部阴性。12例MDI哮喘病人测定了血清总IgE、MDI-HSA(人血清白蛋白)结合物的特异性IgE(S-IgE)和特异性IgG(S-IgG)抗体含量,均显著高于对照组,阳性率分别为66.7％、91.7％和91.7％。10例MDI哮喘病人进行MDI-HSA皮肤挑刺试验,7例阳性,均伴有S-IgE增高;其中呈双相反应的3例,还伴有BHPT阳性和S-IgG增高。未检出血清沉淀素抗体。T细胞ANAE阳性率与对照组无差别(P>0.05)。结果表明,MDI哮喘的发病机理与IgE、IgG介导的变态反应有关,细胞免疫反应无明显影响。     

Exposure assessment and sensitisation in workers exposed to organic acid anhydrides

Objectives: To clarify whether the intensity of exposure to organic acid anhydrides (OAAs) is associated with the risk of sensitisation to these allergens. Methods: The investigations were carried out in three different manufacturing plants (A, B, and C) where OAAs were used in the production of epoxy resins. Methyltetrahydrophthalic acid anhydride (MTHPA) was used in all three plants. The exposure assessment included stationary and ambient air monitoring (OAAs in the air) and biological monitoring (metabolites in urine). In plant A 20, in plant B 86 and in plant C 113 employees were examined by a physician (anamnesis, skin-prick test, specific IgE, spirometry). In plants B and C, the exposure areas were classified as high, medium, and low, without the results of the exposure assessment being known. Results: The ambient air concentrations (in μg/m³) of MTHPA were 37.2 and 58.5 in plant A (number of samples n=2), ranged from <0.5–26.2 in plant B (n=5) and from 2.1–57.9 in plant C (n=3) with stationary air collecting, and from 8–45 (n=6), from <4.7–35.7 (n=3) and from 2–37.8 (n=3) with personal air collection. The metabolites of OAAs in urine (in nmol/mmol creatinine) ranged from 5.7–645 (median of MTHPA: 346) in plant A, from <1–213 (median of MTHPA: 10.1) in plant B and from 0.1–830 (median of the sum of the OOA metabolites: 108.6) in plant C. The prevalence of sensitisation was 35% in plant A, 21% in plant B and 29% in plant C. A higher prevalence in the highly exposed areas, however, could not be seen. Levels of IgE specific for conjugates of MTHPA were not associated with the metabolites in the end of shift urine. Levels of IgG specific for conjugates of MTHPA, however, were associated with the metabolites in the end of shift urine. Conclusions: The data showed that biological monitoring is a useful tool in the exposure assessment of OAAs. Comparing the prevalence of sensitisation and the results of biological monitoring, between the three plants, we found that sensitisation increased with increasing exposure. Within a plant a higher risk of sensitisation in persons working in highly exposed areas at the time of the examination could not be seen, possibly due to frequent job rotation. Received: 2 August 1999 / Accepted: 29 January 2000     

Respiratory and other hazards of isocyanates

Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m³) and 20 ppb (0.14 mg/m³), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1 % of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.Abbreviations ACH acetylcholine - BALF bronchoalveolar lavage fluid - CGRP calcitonin gene-related peptide - cpm counts per minute - DMSO dimethylsulfoxide - EAST enzyme allergo sorbent test - FEV ₁ forced expiratory volume in one second - HDI hexamethylene diisocyanate - HSA human serum albumin - IGV intrahoracic gas volume, measured by bodyplethysmography - IVC inspiratory vital capacity - LC ₅₀ lethal concentration for 50% of tested animals - MDI diphenylmethane diisocyanate - PD _50(100)/PC _50(100) dose/concentration causing a change of 50% (100%) of the parameter indicated - ppb (ppm) parts per billion (million) - RAST radio allergo sorbent test - Raw airway resistance, measured by bodyplethysmography - sRaw specific airway resistance, measured by bodyplethysmography - TDI toluene diisocyanate - TLV threshold limit value These studies were partly supported by the Ministry of Research and Technology, Federal Republic of Germany, grant 07 ALL 16     

哮喘严重程度与血清特异性IgE的关系分析

目的了解不同严重程度哮喘患儿过敏原状况,指导临床防治。方法采用酶联免疫吸附法检测73例不同严重程度哮喘患儿血清过敏原特异性IgE抗体。结果所研究患儿过敏原特异性IgE抗体的阳性率以屋尘和螨虫阳性率最高(屋尘74.0%。户尘螨63·0%);各组患儿总IgE抗体阳性结果差异有统计学意义(2=37·7869,p<0·0001);各组患儿检出过敏原种类差异有统计学意义(2=208437,p=0·0001)。结论屋尘和户尘螨是3岁以上儿童哮喘发作的主要诱因;支气管哮喘患儿的哮喘严重程度与其血清总IgE水平的高低呈正相关;对多种抗原表现特异性IgE阳性者往往病情较重。     

谷物粉尘致豚鼠哮喘模型支气管肺泡灌洗液细胞学和肺组织病理学观察

本文对比观察了用谷尘、青霉菌提取液和卵蛋白致敏并激发后阳性反应豚鼠支气管肺泡灌洗液（ＢＡＬＦ）内细胞学和肺组织病理学变化。结果发现激发试验阳性的谷尘组、青霉菌组和卵蛋白组哮喘模型ＢＡＬＦ内嗜酸细胞数分别为３６．０４±１１．２２％，３２．２１±８．２４％和３０．５０±１０．２０％，均非常显著地高于反应阴性组（１２．５０±７．２９％）和对照组（９．７５±４．０３％），Ｐ＜０．０１。光镜下见反应阳性动物支气管、细支气管痉挛以及壁内和腔内大量炎细胞浸润和粘液栓塞等。电镜下可见以嗜酸细胞为主的炎性细胞及其胞浆内大量特异性颗粒及脱颗粒后形成的空泡等，提示嗜酸细胞在谷物粉尘所致豚鼠哮喘的发病过程中起着重要的作用。