Air Pollution Exposure Laboratory, Division of Respiratory Medicine, Department of Medicine, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Unit of Integrative Metabolomics, Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden; and.
Ann Am Thorac Soc. 2024 Dec;21(12):1715-1722. doi: 10.1513/AnnalsATS.202311-955OC.
Growing evidence suggests that air pollution exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) that is associated with an increased prothrombotic state and adverse cardiovascular outcomes. However, much of this work is based on observational data or human exposure studies involving younger participants. The biological causality and mechanism of air pollution-induced prothrombotic response in patients with COPD remain to be explored. The main aim of this work was to investigate the impact of short-term diesel exhaust (DE) exposure on circulating prothrombotic markers-fibrinogen and plasminogen activator inhibitor-1 (PAI-1)-and urinary eicosanoids in patients with COPD. Twenty-nine research participants were recruited in this randomized, double-blind, crossover, controlled human exposure study to DE. Participants included former smokers with and without mild or moderate COPD (ex-smokers [ES] and COPD group) and healthy never-smokers without COPD (nonsmoker [NS] group). Each participant was exposed to DE (300 μg/m of particulate matter with an aerodynamic diameter ≤2.5 μm) and filtered air for 2 hours on different occasions, in randomized order, separated by a 4-week washout. Blood and urine samples were collected before and 24 hours after each exposure. Plasma fibrinogen and serum PAI-1 concentrations were quantified using enzyme-linked immunosorbent assays. Urinary eicosanoid concentrations were quantified using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Linear mixed-effects models were used for statistical comparisons. Participants with COPD showed an increase in plasma fibrinogen (effect estimate, 1.27 [1.06-1.53]; = 0.01) after DE relative to filtered air, but no significant DE-associated change in serum PAI-1 (0.95 [0.87-1.04]; = 0.26). In never-smokers and ex-smokers without COPD, fibrinogen (NS group, 1.10 [0.99-1.23]; = 0.08; ES group, 0.86 [0.68-1.09]; = 0.08] and PAI-1 (NS group, 1.12 [0.96-1.32]; = 0.15; ES group, 0.90 [0.79-1.03]; = 0.13) were not changed after DE exposure. Participants with COPD showed a DE-attributable increase in urinary thromboxane B2 (TXB) metabolite concentrations as follows: 11-dehydro-TXB (1.45 [1.02-2.08]; = 0.04) and 2,3-dinor-TXB (1.45 [1.05-2.00]; = 0.03). Participants with COPD had increased plasma fibrinogen and urinary TXB metabolites after short-term DE exposure, suggesting they may be more susceptible to a pollution-attributable prothrombotic response than healthy control subjects or ex-smokers without COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).
越来越多的证据表明，空气污染暴露是慢性阻塞性肺疾病（COPD）的一个主要危险因素，与血栓形成状态增加和不良心血管结局有关。然而，这项工作的大部分是基于观察性数据或涉及年轻参与者的人体暴露研究。空气污染引起 COPD 患者血栓形成反应的生物学因果关系和机制仍有待探索。这项工作的主要目的是研究短期柴油机废气（DE）暴露对 COPD 患者循环血栓形成标志物纤维蛋白原和纤溶酶原激活物抑制剂-1（PAI-1）以及尿类二十烷酸的影响。29 名研究参与者被招募到这项随机、双盲、交叉、对照的人体 DE 暴露研究中。参与者包括有或没有轻度或中度 COPD 的前吸烟者（ES 组和 COPD 组）和没有 COPD 的健康从不吸烟者（NS 组）。每个参与者都在不同的时间以随机顺序暴露于 DE（300μg/m 的粒径小于等于 2.5μm 的颗粒物）和过滤空气 2 小时，间隔 4 周洗脱期。暴露前和暴露后 24 小时采集血液和尿液样本。使用酶联免疫吸附试验定量血浆纤维蛋白原和血清 PAI-1 浓度。使用超高效液相色谱-串联质谱法定量尿类二十烷酸浓度。使用线性混合效应模型进行统计比较。与过滤空气相比，COPD 患者在 DE 暴露后血浆纤维蛋白原增加（效应估计值 1.27[1.06-1.53]； = 0.01），但血清 PAI-1 无明显 DE 相关变化（0.95[0.87-1.04]； = 0.26）。在从不吸烟者和没有 COPD 的前吸烟者中，纤维蛋白原（NS 组 1.10[0.99-1.23]； = 0.08；ES 组 0.86[0.68-1.09]； = 0.08）和 PAI-1（NS 组 1.12[0.96-1.32]； = 0.15；ES 组 0.90[0.79-1.03]； = 0.13）在 DE 暴露后没有变化。COPD 患者的尿血栓素 B2（TXB）代谢物浓度有 DE 归因增加，如下：11-脱氢-TXB（1.45[1.02-2.08]； = 0.04）和 2,3-二去氢-TXB（1.45[1.05-2.00]； = 0.03）。与过滤空气相比，COPD 患者在短期 DE 暴露后血浆纤维蛋白原和尿 TXB 代谢物增加，这表明他们可能比健康对照组或没有 COPD 的前吸烟者更容易发生与污染相关的血栓形成反应。这项临床试验已在 www.clinicaltrials.gov 注册（NCT02236039）。
