大氣次微米懸浮微粒對人體心血管系統影響之研究

Studies on the Effects of Ambient Submicrometer Particles on Cardiovascular System Among Human Subjects

莊凱任(Kai-Jen Chuang)

指導教授 ： 詹長權

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/博士(2006年)

https://doi.org/10.6342/NTU.2006.01311

摘要

根據流行病學研究顯示，大氣懸浮微粒的暴露與人體心血管系統不良健康效應的產生、心血管疾病罹病率及死亡率的增加有顯著相關。粒徑較小的微粒如次微米微粒及其不同微粒成分對人體心血管系統的影響則有待釐清。為能了解微粒空氣污染物導致心血管疾病的致病機轉，過去許多個案小組研究針對微粒空氣污染物對心血管系統產生的各種影響包括發炎反應、氧化壓力的產生、凝血功能、自主神經功能等進行研究。微粒空氣污染物是否能同時導致心血管系統各種不良健康效應的發生也有待更進一步。本研究以個案小組研究方法，以患有呼吸道疾病、心血管疾病的病患、以及年輕健康的族群，對其短期暴露於次微米微粒空氣污染物、微粒成分包括硫酸鹽、硝酸鹽、有機碳、元素碳等與人體心血管相關生理指標如血壓、心跳、心跳速率變異性、血液發炎指標高敏感度C反應蛋白、血液凝血指標血纖維蛋白原、血液溶血指標血纖維蛋白溶解酶原活化劑抑制劑第一型及組織型血纖維蛋白溶解酶原活化劑、氧化壓力指標8-氫氧2'-去氧鳥糞核糖等指標變化之相關性進行研究。本研究發現大氣次微米微粒的暴露會導致心跳加快、血壓升高及自主神經功能失調。微粒成分中的硫酸鹽、硝酸鹽、有機碳成分會導致心血管系統凝血、發炎、氧化壓力的產生，以及自主神經功能失調。患有冠狀動脈疾病、高血壓的患者，以及肺功能不良的呼吸道疾病患者為微粒空氣污染物的易感受族群。本研究提供過去流行病學觀察的支持，並提供政府單位未來修訂空氣品質標準之參考依據。

關鍵字

空氣污染 ； 次微米微粒 ； 心血管系統 ； 流行病學

並列摘要

The epidemiological association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well documented in previous studies. The association between smaller PM, such as submicrometer particles, and its components and PM-related cardiovascular effects is still not clear. The plausible mechanisms linking particulate air pollution to cardiovascular events, including inflammation, oxidative stress, blood coagulation and autonomic dysfunction in humans have been separately but not concurrently investigated in previous panel studies. Therefore, the aim of this study was designed to investigate the effects of submicrometer particles and particulate matter components on human cardiovascular system and provide the potential biological evidence on PM-related health effects in humans.
There are parts in this study. Part I, we measured ambulatory systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) by a portable BP monitoring system and number concentrations of submicrometer particle with a size range of 0.02-1 μm (NC0.02-1) by a P-TRAK Ultrafine Particle Counter for 10 patients with lung function impairments. The study results revealed that NC0.02-1 exposures at 1-3 hours moving averages were associated with the elevation of SBP, DBP and HR. There were 1.40-3.40 mm Hg increases in SBP, 1.40-2.20 mm Hg increases in DBP and 0.28-3.50 beats/min increases in HR for 10,000 particles/cm3 increases in NC0.02-1 at 1-3 hour moving averages. Part II, we measured individual’s electrocardiographics (ECG) and PM exposures in 10 patients with coronary heart disease (CHD) and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of NN intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF, 0.04-0.15 Hz), high frequency (HF, 0.15-0.40 Hz) and LF/HF ratio. The pollution variables were mass concentrations of particle with a size range of 0.3-1.0 mm (PM0.3-1.0), 1.0-2.5 mm (PM1.0-2.5), and 2.5-10 mm (PM2.5-10). We used linear mixed-effects models to examine the association between PM exposures and log10-transformed HRV indices with key personal and environmental attributes being adjusted. We found PM0.3-1.0 exposures at 1-4 hours moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM0.3-1.0, there were 1.49-4.88% decreases in SDNN, and 2.73-8.25% decreases in r-MSSD. PM0.3-1.0 exposures were also associated with decreases in LF and HF for hypertensive patients at 1-3 hours moving averages but for cardiac patients at moving averages of 2 or 3 hours. By contrast, we found HRV was not associated with either PM1.0-2.5 or PM2.5-10. Part III, we recruited a panel of 46 patients with or at risk for cardiovascular diseases to measure their 24-hour HRV by ambulatory ECG. Fixed-site air-monitoring stations were used to represent study participants’ exposures to particles with aerodynamic diameters less than 10 mm (PM10) and 10 mm (PM2.5), and particulate components of sulfate, nitrate, organic carbon (OC) and elemental carbon (EC), and gaseous pollutants of nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3). We used linear mixed-effects models to analyze association between individual air pollutants and log10-transformed HRV with key personal and environmental attributes and co-pollutants being adjusted. We found HRV reduction was associated with sulfate, OC and PM2.5 but not with the other five pollutants in single-pollutant models. Sulfate and OC remained significant association with HRV reduction adjusting for PM2.5 in two-pollutant models. An interquartile increase in 3-hour to 4-hour averages of sulfate (14.6 mg/m3) is corresponded to decrease in 7.01-7.70% of SDNN, 14.19-18.18% of r-MSSD, 11.85-13.79% of LF and 16.03-20.77% of HF. An interquartile increase in 4-hour average of OC (7.8 mg/m3) was associated with 3.69%, 5.25% and 7.51% decrease in SDNN, r-MSSD and HF, respectively. Only sulfate remained significant association with HRV reduction adjusting for PM2.5, sulfate and OC in three-pollutant models. Part IV, we recruited a panel of 76 young and healthy students from a university in Taipei, measuring their high sensitivity-C-reactive protein (hs-CRP), 8-hydroxy-2’-deoxyguanosine (8-OHdG), plasminogen activator fibrinogen, inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA) and HRV on each participant for three times from April to June in the years 2004 and 2005. Ambient concentrations of gaseous air pollutants were measured at one air-monitoring station inside their campus, and particulate air pollutants were measured at one particulate matter Supersite monitoring station 1km from their campus. We used linear mixed-effects models to associate health outcomes with individual air pollutants at 1-day to 3-day averages adjusting for key personal attributes, temperature, humidity and co-pollutants. We found increases in hs-CRP, 8-OHdG, fibrinogen, PAI-1, and decreases in HRV indices were associated with increases in ambient concentrations of PM10 and PM2.5, sulfate, nitrate and O3 at 1-day to 3-day averages in single-pollutant models. The increase in 8-OHdG, fibrinogen and PAI-1, and HRV reduction remained significant association with 3-day averaged sulfate and O3 in two-pollutant models. There were moderate correlations (r = -0.3) between blood markers of hs-CRP, fibrinogen, PAI-1, and HRV indices in our participants.
Taken overall, our study findings provided evidence for the biological plausibility of PM related health effects on cardiovascular and autonomic system and supported previous hypothesis of pathophysiological pathways, including inflammation, oxidative stress, fibrinolysis and coagulation. Sulfate, nitrate and OC are the major components in PM contributing to cardiovascular effects in humans.

並列關鍵字

air pollution ； submicrometer particles ； cardiovascular system ； epidemiology

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