Ke li wu kong qi wu ran, xi tong yan zheng yu si wang lu: yi xiang Taiwan dui lie yan jiu

Ph.D.Background: Exposure to particulate matter (PM) air pollution is associated with increased risks of cardiovascular morbidity and mortality. However, the underlying mechanisms are not fully understood and PM-induced systemic inflammation has been hypothesized as a main pathway. In a large Taiwanese cohort, we investigated: (1) the association between long-term exposure to PM with an aerodynamic diameter less than 2.5 μm (PM₂.₅) and mortality; (2) the association between long-term exposure to PM₂.₅ and systemic inflammation; (3) whether the effects of PM₂.₅ exposure were modified by physical activity (PA); and (4) the association between systemic inflammation and mortality.Methods: We studied adult participants from a cohort consisting of Taiwanese residents who participated in a standard medical examination program from 1996 to 2014. Twoyear average concentrations of ambient PM2.5 were estimated at each participant`s address using a spatio-temporal model based on satellite-derived aerosol optical depth data. All-cause mortality was ascertained from the Taiwan National Death File. Systemic inflammation was measured by two markers, high-sensitivity C-reactive protein (CRP) and peripheral white blood cell (WBC) count. Differential WBC counts in addition to total WBC count were used in systemic inflammation-mortality analysis. Information on PA was collected by questionnaire. Mixed-effects linear regression, multivariable linear regression and Cox proportional hazard regression were used when appropriate.Results: (1) A total of 297,702 participants were included in PM₂.₅-mortality analysis and 4347 cases of death were identified. Every 5 μg/m³ increment in 2-year average PM₂.₅ was associated with a 5% increased risk of all-cause mortality [hazard ratio (HR): 1.05, 95% confidence interval (CI): 1.03, 1.07] after adjustment for a wide range of potential confounders. (2) A total of 30,034 participants with 39,096 measurements and 359,067 participants with 782,404 measurements were included in the PM₂.₅-CRP analysis and PM2.5-WBC analysis, respectively. Every 5 μg/m3 PM2.5 increment was associated with 1.31% increase in CRP (95% CI: 1.00%, 1.63%) and 0.19% (95% CI: 0.17%, 0.21%) increase in WBC count after adjustment for confounders; (3) PA was associated with reduced risk of death and decreased CRP and WBC count. No consistent interactions between PM2.5 and PA were detected. (4) Among 392,853 study participants included in WBC-mortality analysis, higher total WBC count, neutrophil, monocyte and neutrophil/lymphocyte ratio were associated with increased risk of death. Lymphocyte was negatively associated with the risk of death in women, but not in men.Conclusions: Our study showed that long-term PM₂.₅ exposure is associated with increased systemic inflammation levels and increased systemic inflammation is associated with increased risk of mortality. Long-term PM2.5 exposure is also directly associated with increased risk of mortality. In addition, the adverse effects of PM₂.₅ exposure are not modified by habitual PA. These findings support that PM-induced inflammation is a major biological mechanism underlying the adverse effects of PM air pollution. We advocate global strategies on air pollution mitigation and PA promotion to prevent premature death.背景: 顆粒物（PM）空氣污染和心血管疾病發病率和死亡率相關聯，但是，潛在作用機制尚不明確。PM 導致的系統炎症可能是一個重要機制。本研究基於一項台灣人群隊列，旨在調查：（1）長期暴露於細顆粒物（空氣動力學直徑小於 2.5微米的顆粒物，PM₂.₅）與死亡率的關系；（2）長期暴露於 PM₂.₅ 與系統驗證的關系； （3）PM2.5 的效應是否會被日常體力活動（PA）增強；以及（4）系統炎症與死亡率的關系。方法: 研究對像來自一項台灣的大項隊列研究。該研究由 1996 年至 2014 年之間參加一項標准醫學體檢項目的台灣居民組成。時空模型被用於計算位於每個研究對像地址的 2 年平均室外 PM₂.₅ 濃度。該模型的建立基於由衛星遙感技術測量的大氣氣溶膠光學厚度數據。全死因死亡率來源於台灣居民死因數據。系統炎症通過高敏 C 反應蛋白（CRP）和白細胞（WBC）計數兩項指標測量。除 WBC 總計數外，WBC 分類計數亦被用於系統炎症和死亡率的研究分析。研究對像日常 PA的信息則由問卷收集。根據不同的數據，統計分析使用混合效應線性回歸模型﹑多元線性回歸模型或 Cox 風險比例回歸模型。結果: （1）一共 297,702 研究對像被納入到 PM₂.₅ 和死亡率的分析。研究期間觀測到 4347 个死亡案例。在校正混雜因素後，PM2.5 濃度每上升 5 微克/立方米（μg/m3），全死因死亡風險升高 5%【風險比（HR）:1.05，95%置信區間（CI）: 1.03，1.07】；（ 2）30,034 名和 359,067 名研究對像分布被納入到 PM₂.₅ 和 CRP 以及 PM₂.₅ 和 WBC 計數的研究中。PM₂.₅ 濃度每上升 5 μg/m³，CRP 和 WBC 計數分別上升 1.31% (95% CI: 1.00%, 1.63%)和 0.19% (95% CI: 0.17%, 0.21%)；（ 3）日常 PA 和全死因死亡風險以及 CRP/WBC 均呈負相關。本研究沒有觀測到顯著的PM2.5 和 PA 交互作用；（4）在 392,853 名納入到 WBC-死亡率分析的研究對像中，WBC 總計數﹑中性粒細胞﹑單核細胞以及中性粒細胞/淋巴細胞比值均和全死因死亡風險正相關。淋巴細胞則和死亡風險負相關，該相關只在女性研究對像中呈現。結论: 本研究發現長期暴露於 PM₂.₅ 能激活機體系統炎症，而系統炎症水平的升高會導致死亡風險的升高。同時，PM2.5 和死亡風險直接相關。此外，我們發現日常 PA 不會增強 PM₂.₅ 空氣污染的有害效應。本研究支持系統炎症是連接 PM空氣污染和死亡的重要機制的假說。降低空氣污染和增加體育鍛煉應作為預防過早死亡的有力措施而廣泛推廣。Zhang, Zilong."November 2017."Thesis Ph.D. Chinese University of Hong Kong 2018.Includes bibliographical references (leaves 116-133).Abstracts also in Chinese.Title from PDF title page (viewed on 19, April, 2021).Zhang, Zilong