BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China.
Hebei Technology Innovation Center of Human Settlement in Green Building (TCHS), Shenzhen Institute of Building Research Co., Ltd., Xiongan, China.
Part Fibre Toxicol. 2022 Oct 24;19(1):65. doi: 10.1186/s12989-022-00503-9.
Exposure to particulate matter air pollution is associated with an increased risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not yet understood. Enhanced platelet and pro-thrombotic activity in COPD patients may explain their increased cardiovascular risk. We aim to explore whether short-term exposure to ambient particulate matter is associated with pro-thrombotic changes in adults with and without COPD, and investigate the underlying biological mechanisms in a longitudinal panel study. Serum concentration of thromboxane (Tx)B2 was measured to reflect platelet and pro-thrombotic activity. Lipoxygenase-mediated lipid peroxidation products (hydroxyeicosatetraenoic acids [HETEs]) and inflammatory biomarkers (interleukins [ILs], monocyte chemoattractant protein-1 [MCP-1], tumour necrosis factor alpha [TNF-α], and macrophage inflammatory proteins [MIPs]) were measured as potential mediating determinants of particle-associated pro-thrombotic changes.
53 COPD and 82 non-COPD individuals were followed-up on a maximum of four visits conducted from August 2016 to September 2017 in Beijing, China. Compared to non-COPD individuals, the association between exposure to ambient ultrafine particles (UFPs) during the 3-8 days preceding clinical visits and the TxB2 serum concentration was significantly stronger in COPD patients. For example, a 10/cm increase in the 6-day average UFP level was associated with a 25.4% increase in the TxB2 level in the COPD group but only an 11.2% increase in the non-COPD group. The association in the COPD group remained robust after adjustment for the levels of fine particulate matter and gaseous pollutants. Compared to the non-COPD group, the COPD group also showed greater increases in the serum concentrations of 12-HETE (16.6% vs. 6.5%) and 15-HETE (9.3% vs. 4.5%) per 10/cm increase in the 6-day UFP average. The two lipid peroxidation products mediated 35% and 33% of the UFP-associated increase in the TxB2 level of COPD patients. UFP exposure was also associated with the increased levels of IL-8, MCP-1, MIP-1α, MIP-1β, TNF-α, and IL-1β in COPD patients, but these inflammatory biomarkers did not mediate the TxB2 increase.
Short-term exposure to ambient UFPs was associated with a greater pro-thrombotic change among patients with COPD, at least partially driven by lipoxygenase-mediated pathways following exposure. Trial registration ChiCTR1900023692 . Date of registration June 7, 2019, i.e. retrospectively registered.
暴露于颗粒物空气污染与慢性阻塞性肺疾病（COPD）患者的心血管死亡率增加有关，但潜在机制尚不清楚。COPD 患者的血小板和促血栓形成活性增强可能解释了其心血管风险增加。我们旨在探讨短期暴露于环境颗粒物是否与有和没有 COPD 的成年人的促血栓形成变化有关，并在一项纵向面板研究中研究潜在的生物学机制。测量血栓烷（Tx）B2 的血清浓度以反映血小板和促血栓形成活性。测量脂氧合酶介导的脂质过氧化产物（羟二十碳四烯酸[HETEs]）和炎症生物标志物（白细胞介素[ILs]、单核细胞趋化蛋白-1 [MCP-1]、肿瘤坏死因子 alpha [TNF-α]和巨噬细胞炎症蛋白[MIPs]）作为与颗粒相关的促血栓形成变化的潜在中介决定因素。
2016 年 8 月至 2017 年 9 月期间，在中国北京，最多对 53 名 COPD 患者和 82 名非 COPD 患者进行了 4 次随访。与非 COPD 个体相比，暴露于临床就诊前 3-8 天环境超细颗粒（UFPs）与 COPD 患者 TxB2 血清浓度之间的相关性更强。例如，在 COPD 组中，6 天平均 UFP 水平每增加 10/cm，TxB2 水平增加 25.4%，而非 COPD 组仅增加 11.2%。在调整细颗粒物和气态污染物水平后，COPD 组的相关性仍然很强。与非 COPD 组相比，COPD 组的 12-HETE（16.6%比 6.5%）和 15-HETE（9.3%比 4.5%）血清浓度也分别增加了 10/cm 的 6 天 UFP 平均值。这两种脂质过氧化产物介导了 COPD 患者中 UFP 相关 TxB2 水平增加的 35%和 33%。UFPs 暴露也与 COPD 患者中白细胞介素-8、MCP-1、MIP-1α、MIP-1β、TNF-α和白细胞介素-1β水平的升高有关，但这些炎症生物标志物并没有介导 TxB2 的增加。
短期暴露于环境 UFPs 与 COPD 患者的促血栓形成变化更大有关，至少部分原因是暴露后脂氧合酶介导的途径。试验注册 ChiCTR1900023692. 登记日期 2019 年 6 月 7 日，即回溯性注册。
