抽象
一名43岁男性患者有6个月的咳嗽、呼吸短促和发烧病史。他稍有用力就呼吸困难。这名患者在一家牛饲料工厂工作,他注意到下班后投诉更多。他的症状可能是由于接触了植酸酶引起的过敏性肺炎。植酸酶是一种添加到牛饲料中的酶,用于强化骨骼和减少磷的排泄。
体格检查发现双基性肺裂,限制性通气缺陷(一氧化碳弥散能力下降),典型x线表现,支气管肺泡灌洗液淋巴细胞增多症,工作场所暴露试验阳性。血液检查显示植酸酶免疫球蛋白G水平高。
植酸酶接触的治疗和戒烟后病人症状变得自由和肺功能恢复正常。植酸酶应被视为职业过敏的原因在饲料行业肺炎。
案例报告
没有事先生病43年之久的男子被提到我们对未成年人劳累,发烧及不适(尤其是疲劳)咳嗽和气短症状部门的门诊。He had lost 8 kg of weight since his complaints had started 6 months earlier and had been a non-smoker for 20 yrs. There was a relationship between his complaints and his working hours. He had worked in a factory that produces cattle feed for >20 yrs where his role was to take samples of the cattle feed at different departments on different floors for quality control. He noticed that after having taken samples on one particular floor, 6–8 h later, his complaints started. The next morning the complaints had almost disappeared. He had no symptoms during the holidays. None of his colleagues (n = 21) had similar symptoms.
体检时脉搏和血压正常。肺部听诊时可听到正常的呼吸声,但伴有双基底爆裂声。红细胞沉降率为33 mm·h−1c反应蛋白为11 mg·L−1(正常范围:< 10mg·L−1)。血液白细胞,总免疫球蛋白(Ig)E,抗核抗体和特异性IgE常见过敏原均内的参考值。
胸片显示特别是在较低的肺野增加不明确的实质混浊。该high-resolution computed tomography of the thorax showed a uniform distribution of ill-defined centrilobular nodules with mainly ground-glass pattern (fig. 1⇓)。
肺功能测试,根据欧洲共同体对煤和钢的预测值1,显示出与一氧化碳降低扩散容量温和限制性图案。该vital capacity (VC) was 4.6 L (82% predicted), total lung capacity (TLC) was 6.0 L (75% pred) and diffusing capacity of the lungs (Dl)为6.2 mmol·min−1·帕−1(51%预解码值)。During exercise testing on a cyclometer the patients’ maximum load was 180 W (77% pred) and oxygen tension decreased during exercise from 10.99 kPa to 7.19 kPa.
特定的工厂车间,气雾化植酸酶(汽化的植酸酶的帘幕)在封闭系统中被添加到动物饲料通过传送带。当取样品,病人没戴呼吸防护装置。
因为他的症状与他的植酸酶工作的暴露试验是在工作场所进行。During this test the patient took samples of pig's feed for 10 min from the area where the feed is carried through a curtain of vaporised phytase by a conveyor. He did not do any other work on that particular day.
He developed progressive dyspnoea on exertion, fever (up to 38.5°C) with malaise, nausea and vomiting 6 h after the exposure. The following morning bronchoalveolar lavage (BAL) was performed2。升高的细胞的总数量(40×106 cells·mL−1),特别是嗜中性粒细胞(37.6%)和淋巴细胞(38%)的数目,以降低的CD4 / 0.53 CD8比率。巨噬细胞(21%)的嗜酸性粒细胞和(4%)的百分数都升高。
To demonstrate inhalable phytase concentrations in the air, especially on that particular floor, airborne inhalable dust was sampled on Teflon filters (10 filters, 2.8–7.6 h sampling time) on various floors of the factory with stationary Gilian pumps (Sensidyne, Clearwater, FL, USA) and PAS-6 sampling heads (IRAS, Utrecht, The Netherlands). The dust was weighed, extracted and measured with a sandwich enzyme immunoassay based on黑尼日尔肌醇六磷酸酶特异的兔抗体3.,但与植酸酶,在工厂使用,生产中里氏木霉(Finase®升;贝恩迈耶梳邦再也,马来西亚)作为标准。该里氏木霉用于生产Finase®的菌株所含的基因用于从3-肌醇六磷酸酶泡盛曲霉。使用抑制实验用兔抗体,由两个曲霉属的植酸酶之间的交叉反应性可以证明(数据未显示)。With Finase® L as a standard, the limit of detection was 1.3 ng·mL−1(or 3.4 ng·m−38小时取样)。On the floor of the factory where Finase® L was added, the inhalable dust concentration was 0.5–1.1 mg·m−3while the phytase concentration was 8.7–38.4 µg·m−3(16.5 - -38.7µg·毫克−1,n = 8). On the other floors, phytase concentrations were much lower (6–58 ng·m−3,1- - - - - -18 ng·mg−1,n = 2). IgG and IgE levels against different antigens4(table 1⇓)通过UNICAP 100(Phadia,弗赖堡,德国)患者的血清中进行测量。
该patient was treated with steroids (prednisone, 30 mg·day−1) for 1 week and with beclomethasone 200 µg twice daily by aerosol inhalation. The patient's symptoms decreased. While at work, he started to wear a protective mask (Arteli Virgo FFP3/v-EN149;2001-FFP3-CE-0086). A repeated chest radiograph and lung function test 2 months after treatment were normalised. The VC had improved to 5.8 L (103% pred), TLC was 7.6 L (90% pred) and Dl7.5摩尔·敏吗−1·帕−1(62%预解码值)。
讨论
病人的病史,bibasal听诊肺部发出爆裂声,限制性肺功能模式为一氧化碳扩散能力下降,氧张力减少努力,辐射特性,增加了特定的免疫球蛋白g植酸酶,和积极的曝露试验(包括球结果),所有支持的诊断过敏性肺炎(HP)5- - - - - -7。此外,治疗和接触对植酸酶释放后的临床症状改善强烈建议HP由于植酸酶的吸入。据我们所知,这从未有过报道。
植酸酶是一种酶,催化水解植酸,一种存在于谷物和大豆中的磷酸盐储存模式,无机磷酸盐。单胃动物(猪和家禽)只能部分利用这种形式的磷。为了提高这些动物对磷的生物利用度,饲料中添加了真菌植酸酶。这导致减少了无机磷的添加需求,减少了粪便磷的排泄8,9。
我们的数据显示,与植酸酶接触和病人的症状之间有很强的关系。即使暴露试验是在工作场所,而不是一个实验室,积极激发试验,从工厂和患者的高度特异性IgG的曝光测量数据进行泡盛曲霉植酸酶生产的里氏木霉对于植酸酶和疾病之间的关系,有力的论据。
虽然患者有对植酸酶产品极高的IgG水平,他只针对中等IgG水平烟熏鱼和模具混合物。因此,它似乎是不可能的HP是由“模子”或“模具污染”造成的。
戴着呼吸装置,如HP一种保护措施的积极作用尚未证实10。在职业性哮喘中,佩戴呼吸装置可以减轻呼吸道症状,但不能提供完全的保护11,12。在我们的病例中,患者在接受治疗后和戴上防护口罩后没有表现出任何呼吸道症状。
以前没有研究或病例报告描述了HP和植酸酶或其他磷酸水解之间的关系。然而,也有描述植酸酶的原因(过敏性)呼吸道症状少数研究。这样做的原因可能是植酸酶作为添加剂一直只从90年代初期使用。Doekeset al。13描述了暴露于植酸酶黑曲霉可引起IgE过敏、职业性哮喘等呼吸道症状。奥康纳et al。14经特异性支气管挑战证实,植酸酶可引起职业性哮喘。此外,鲍尔et al。9证实粉状植酸酶源自黑曲霉是一种高致敏性物质,近日,卡瓦列罗et al。15结果表明,来自Peniophora和Trichoderma的植酸酶在动物饲料行业工作者中引起了ige介导的过敏。在本例中,致敏的植酸酶为an泡盛曲霉3-植酸酶表达里氏木霉。通过对开发的兔抗体在职场中检测到这种酶黑曲霉植酸酶。作为这些酶的氨基酸序列是> 97%相同,也难怪这些抗体,另外,患者的IgG抗体反应,以来自两个物种植酸酶。Airborne phytase concentrations at the patient's workplace reached 38.4 µg·m−3这远远高于,例如,蛋白酶在洗涤剂工业中的浓度16。这种暴露在夜间仅采集样本10分钟后就出现严重症状,而高抗原暴露也可能是该患者发病机制中的重要一步。HP主要是由高污染地区的病原体引起的。在我们的案例中,与工厂内的其他地方相比,工作区域含有高水平的病原体。
相较于已经在文献中描述的情况下,我们的病人没有发展介导的过敏植酸酶,但过敏性肺炎的免疫球蛋白E。
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- 收到2008年3月7日。
- 接受2009年1月5日。
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