Air Pollution Exposure Laboratory, Department of Medicine, Vancouver Coastal Health Research Institute, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
Centre for Heart Lung Innovation, St. Paul's Hospital, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
Thorax. 2020 Aug;75(8):640-647. doi: 10.1136/thoraxjnl-2020-214561. Epub 2020 May 28.
Exposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways.
Fourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators.
In human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV.
Short-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion.
NCT02017431.
暴露于空气污染与哮喘发病率和死亡率的增加有关。为了了解将空气污染和过敏原暴露与哮喘病理生理学联系起来的病理过程，我们研究了共暴露于柴油机排气（DE）和空气过敏原对人体气道中免疫调节蛋白的影响。
14 名过敏原致敏的参与者完成了这项随机、双盲、交叉、对照暴露研究。每个参与者都在不同的日期进行了四次暴露（过敏原单独暴露、DE 和过敏原共暴露、颗粒耗尽的 DE（PDDE）和过敏原共暴露以及假暴露），每次暴露之间间隔 4 周洗脱期。血清和支气管肺泡灌洗液（BAL）用于检测模式识别分子、细胞因子、趋化因子和炎症介质。
在人体气道中，过敏原单独暴露导致表面活性剂蛋白 D（SPD；p=0.02）积累。与单独过敏原暴露相比，共暴露于过敏原和 DE 并没有引起 SPD 的相同增加；减少颗粒恢复了过敏原诱导的 SPD 积累。与没有颗粒减少相比，可溶性晚期糖基化终产物受体更高。在全身循环中，单独过敏原 4 小时后 SPD 和 club 细胞蛋白 16（CC16）有短暂增加。PDDE 增强了 CC16，但 DE 没有。BAL 中的嗜酸性粒细胞百分比（p<0.005）、嗜酸性粒细胞趋化因子-3（eotaxin-3；p<0.0001）、白细胞介素 5（IL-5；p<0.0001）和胸腺激活调节趋化因子（p=0.0001）均在 BAL 中增加。BAL 中的 IL-5、SPD 和嗜酸性粒细胞百分比与 FEV 降低相关。
短期共暴露于空气过敏原和 DE 会改变肺部的免疫调节蛋白；表面活性剂水平取决于颗粒耗竭。
NCT02017431。
