O'Sullivan S, Dahlen S E, Larsson K, Larsson B M, Malmberg P, Kumlin M, Palmberg L
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Thorax. 1998 Dec;53(12):1041-6. doi: 10.1136/thx.53.12.1041.
Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear.
Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E4 (LTE4) and 9 alpha, 11 beta-PGF2, the earliest appearing urinary metabolite of prostaglandin D2 (PGD2), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure.
Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p < 0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and prechallenge levels of LTE4 (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p < 0.01) and 9 alpha, 11 beta-PGF2 (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p < 0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively.
The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.
健康受试者急性暴露于猪舍灰尘中会导致支气管对乙酰甲胆碱的反应性增加，但不会引起急性支气管收缩。半胱氨酰白三烯和肥大细胞在支气管反应性增加中的作用尚不清楚。
10名非哮喘受试者在猪场称猪时暴露于猪灰尘中3小时。在进入猪场之前、进入猪场后长达12小时以及暴露前5天和暴露后当天的同一时间收集尿液。作为全身白三烯产生和肥大细胞活化的指标，测量尿中白三烯E4（LTE4）和9α,11β -前列腺素F2（9α,11β -PGF2，前列腺素D2（PGD2）最早出现的尿代谢产物）的水平。在暴露前5天和暴露后当天测定支气管对乙酰甲胆碱的反应性。
乙酰甲胆碱PD20FEV1从暴露前的1.32毫克（95%可信区间0.22至10.25）降至暴露后的0.38毫克（95%可信区间0.11至1.3）（p < 0.01）。与支气管反应性增加相关的是，暴露于猪灰尘当天，LTE4的激发后和激发前水平之间存在显著平均差异（差异为38.5纳克/毫摩尔肌酐（95%可信区间17.2至59.8）；p < 0.01），9α,11β -PGF2也有显著差异（差异为69纳克/毫摩尔肌酐（95%可信区间3.7至134.3）；p < 0.05）。暴露于猪灰尘导致鼻灌洗液中细胞总数增加24倍，IL -8水平增加12倍。暴露后鼻灌洗液中LTB4和LTE4水平也分别增加了5.5倍和2倍。
本研究结果表明，半胱氨酰白三烯和其他肥大细胞介质有助于吸入有机猪灰尘后支气管反应性增加的发生。
