柴油尾气增加过敏性患者过敏原诱导的下气道炎症：一项对照暴露人类研究
2016/04/28
摘要
背景：研究表明交通相关空气污染会增加过敏与气道疾病。然而，尤其在人体肺内由柴油尾气引起的过敏反应是否增强还未被证实，以及这种明显协同作用的潜在机制也未得到证实。
目的：验证过敏性患者吸入柴油尾气2小时后经节段性过敏原激发可能会增加下气道过敏性炎症以及免疫细胞活化的假设。
方法：18名盲选的过敏性受试者通过随机的方式暴露于滤过的空气或300 µg PM2.5/m3的柴油尾气。暴露1小时后，进行节段性过敏原激发试验作为稀释对照；2天后，利用支气管肺泡灌洗技术从被激发的肺段取得标本。标本用来分析过敏性炎症（嗜酸性粒细胞、Th2细胞因子）的标志物和修饰基因，以及获得性免疫细胞活化。顺序对照的混合效应模型将单独、联合暴露效应的终点指标进行比较。
结果：柴油尾气协同增强过敏原介导的气道嗜酸性粒细胞、白介素5（IL-5）和嗜酸性粒细胞阳离子蛋白（ECP）的增加；并且T1型谷胱甘肽巯基转移酶（GSTT1）缺失型基因型与IL-5效应增强明显相关。单独暴露于柴油尾气也增加了非过敏性炎症标志物和单核细胞趋化因子（MCP）-1，但抑制了巨噬细胞和髓源性树突状细胞的活化。
结论：吸入环境相关浓度的柴油尾气会增加过敏性患者过敏原诱导的下气道过敏性炎症，并且GSTT1基因型会增强该效应。过敏性患者是一类更容易受到柴油尾气的有害气道效应的人群。
Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study
Carlsten C, Blomberg A, Pui M, Sandstrom T, Wong SW, Alexis N, Hirota J.
Thorax ; 2016; 71: 35–44.
ABSTRACT
Rationale: Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood.
Objective: To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.
Methods: 18 blinded atopic volunteers were exposed to filtered air or 300 mg PM2.5/m3 of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.
Results: Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.
Conclusions: Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.
背景：研究表明交通相关空气污染会增加过敏与气道疾病。然而，尤其在人体肺内由柴油尾气引起的过敏反应是否增强还未被证实，以及这种明显协同作用的潜在机制也未得到证实。
目的：验证过敏性患者吸入柴油尾气2小时后经节段性过敏原激发可能会增加下气道过敏性炎症以及免疫细胞活化的假设。
方法：18名盲选的过敏性受试者通过随机的方式暴露于滤过的空气或300 µg PM2.5/m3的柴油尾气。暴露1小时后，进行节段性过敏原激发试验作为稀释对照；2天后，利用支气管肺泡灌洗技术从被激发的肺段取得标本。标本用来分析过敏性炎症（嗜酸性粒细胞、Th2细胞因子）的标志物和修饰基因，以及获得性免疫细胞活化。顺序对照的混合效应模型将单独、联合暴露效应的终点指标进行比较。
结果：柴油尾气协同增强过敏原介导的气道嗜酸性粒细胞、白介素5（IL-5）和嗜酸性粒细胞阳离子蛋白（ECP）的增加；并且T1型谷胱甘肽巯基转移酶（GSTT1）缺失型基因型与IL-5效应增强明显相关。单独暴露于柴油尾气也增加了非过敏性炎症标志物和单核细胞趋化因子（MCP）-1，但抑制了巨噬细胞和髓源性树突状细胞的活化。
结论：吸入环境相关浓度的柴油尾气会增加过敏性患者过敏原诱导的下气道过敏性炎症，并且GSTT1基因型会增强该效应。过敏性患者是一类更容易受到柴油尾气的有害气道效应的人群。
(马利 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（Carlsten C, Blomberg A, Pui M, Sandstrom T, Wong SW, Alexis N, Hirota J.Thorax ; 2016; 71: 35–44.）
（Carlsten C, Blomberg A, Pui M, Sandstrom T, Wong SW, Alexis N, Hirota J.Thorax ; 2016; 71: 35–44.）
Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study
Carlsten C, Blomberg A, Pui M, Sandstrom T, Wong SW, Alexis N, Hirota J.
Thorax ; 2016; 71: 35–44.
ABSTRACT
Rationale: Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood.
Objective: To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects.
Methods: 18 blinded atopic volunteers were exposed to filtered air or 300 mg PM2.5/m3 of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points.
Results: Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells.
Conclusions: Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust.
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