大气颗粒物及多环芳烃暴露与慢性阻塞性肺疾病患者全身性氧化应激水平

目的：研究环境大气颗粒物及多环芳烃（polycyclic aromatic hydrocarbons, PAHs）暴露对慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）患者全身性氧化应激水平的影响。方法：招募45名居住在北京大学医学部半径5 km范围内的COPD患者作为研究对象，采用定组研究方法，于2014年11月至2015年5月对研究对象进行两次临床随访。通过肺功能检查测定第1秒用力呼气容积占预计值百分比（即FEV1%预计值），用于评估COPD患者病情的严重程度。收集患者尿样，分别采用高效液相色谱（high performance liquid chromatography, HPLC）法和酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）法测定尿样中的全身性氧化应激指标丙二醛（malondialdehyde, MDA）和8-羟基脱氧鸟苷（8-hydroxyl-2′-deoxyguanosine, 8-OHdG）水平，同时，通过本课题组于校园内自行建立的空气污染监测站点连续收集研究期间该区域的环境大气污染物浓度以获得人群污染物暴露水平。利用线性混合效应模型，分别通过单污染物模型、双污染物模型和分层分析来研究大气污染物对COPD患者尿样中MDA和8-OHdG水平的影响。结果：滞后2 d（lag2）的超细颗粒物（ultrafine particles, UFP）和PAHs浓度与尿样中MDA水平呈显著正相关（P＜0.05），UFP和PAHs每升高四分位间距（interquartile range, IQR）浓度，MDA浓度分别升高28%（95%CI: 4%~57%）和36%（95%CI: 4%~77%）， 控制黑碳（black carbon, BC）的影响后，UFP和PAHs与MDA的关联强度略有升高。以COPD的严重程度进行分层分析后发现，多数污染物在疾病程度较轻的COPD患者中具有更强的氧化应激效应。在FEV1%预计值≥50%的COPD患者中发现，UFP每升高IQR浓度，尿样中MDA浓度升高98%（95%CI: 38%~186%），BC、UFP和PAHs每升高IQR浓度，尿样中8-OHdG浓度分别升高87%（95%CI: 32%~166%）、69%（95%CI: 24%~130%）和156%（95%CI: 66%~294%）。本研究未观察到细颗粒物（fine particulate matter, PM2.5）与尿样中氧化应激指标的显著关联。结论：大气污染物暴露可加重COPD患者全身性氧化应激水平，其中UFP和PAHs的效应更为显著，并且污染物对于疾病程度较轻的COPD患者氧化应激效应更强。

Effects of exposure to ambient particulate matter and polycyclic aromatic hydrocarbons on oxidative stress biomarkers in the patients with chronic obstructive pulmonary disease

Objective：To investigate the effects of exposure to ambient particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) on systemic oxidative stress biomarkers in chronic obstructive pulmonary disease (COPD) patients. Methods: A panel of forty-five diagnosed and stable COPD patients, whose residences were within 5 kilometers from Peking University Health Science Center (PKUHSC), were recruited and followed up twice between November 2014 and May 2015. The lung function index percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), was measured to reflect the severity of COPD patients. The systemic oxidative stress biomarkers malondialdehyde (MDA) and 8-hydroxyl-2′-deoxyguanosine (8-OHdG) in their urine samples were measured using high performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. Concentrations of ambient air pollutants and levels of meteorological factors were measured continuously through the air pollution-monitoring station located in PKUHSC. PM2.5 samples, which were used for measuring the concentrations of PAHs, were collected by PM2.5 high volume air sampler. We constructed linear mixed-effects models, including single-pollutant model, 2-pollutant models and stratification analysis, to estimate the effects of air pollutants on urinary MDA and 8-OHdG after adjusting for confounding factors. Results: In our COPD-patient panel, the associations between ultrafine particles (UFP) and PAHs and urinary MDA were statistically significant at lag2 (P<0.05). For an interquartile range (IQR) increase in UFP and PAHs, respective increases of 28% (95%CI: 4%－57%) and 36% (95%CI: 4%－77%) in urinary MDA were observed, and the effects became stronger after adjusting for the concentration of black carbon (BC). The COPD patients were divided into 2 groups stratified by FEV1%pred. Most air pollutants had stronger effects of systemic oxidative stress in the COPD patients of FEV1%pred≥50%. In this group, we observed that an IQR increase in UFP was associated with a 98% (95%CI: 38%－186%) increase in urinary MDA, and an IQR increase in BC, UFP and PAHs were associated with respective increases of 87% (95%CI: 32%－166%), 69% (95%CI: 24%－130%) and 156% (95%CI: 66%－294%) in urinary 8-OHdG. We didn’t find significant associations between fine particulate matter (PM2.5) and urinary oxidative stress biomarkers. Conclusion: Our results suggested that exposure to air pollutants, especially UFP and PAHs, was responsible for exacerbation of systemic oxidative stress in COPD patients. Most air pollutants had stronger effects of systemic oxidative stress in mild to moderate COPD patients.