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1 大气污染对慢性阻塞性肺疾病住院影响的 # Meta- 分析李春艳 1, 周丽婷 1, 叶琳 1 2**, 王树越 (1. 吉林大学公共卫生学院劳动卫生与环境卫生学教研科室, 吉林长春 ; 2. 吉林大学中日联谊医院急诊科, 吉林长春 ) 摘要 : 目的 : 采用 Meta- 分析的方法系统评价大气污染对慢性阻塞性肺疾病 (COPD) 住院影响, 为城市大气污染物健康危险度评价工作提供依据方法 : 全面检索 Pubmed Medline 医学数据库中国期刊全文数据库 (CNKI) 万方数据库和维普数据库, 搜集国内外关于空气污染暴露对 COPD 住院影响的病例交叉研究和时间序列研究, 提取文献中相关的数据采用 RevMan 5.0 统计软件评价国内外大气污染物暴露与 COPD 住院人次的暴露 - 反应关系结果 : 共纳入 11 篇文献, 累计病例 1,128,241 例 Meta 分析结果显示, 大气 PM2.5 PM10 SO2 NO2 O3 每升高 10 μg/m3,co 每升高 1mg/m3 居民 COPD 住院百分比分别上升 0.05% 0.08% 0.09% 0.24% 0.05% 0.18% 结论: 大气污染物对居民 COPD 住院产生影响关键词 : 大气污染物 ; 慢性阻塞性肺疾病 ; 病例交叉研究 ; 时间序列研究 ;Meta- 分析中图分类号 :R56 Effect of Air Pollution on Daily Hospitalization of COPD:Meta-analysis LI Chunyan 1, ZHOU Liting 1, YE Lin 1, WANG Shuyue 2 (1. Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun , China; 2. Department of Emergency, China-Japan Union, Jilin University, Changchun , China) Abstract: To evaluate the relationship between air pollution and daily hospitalization for chronic obstructive pulmonary disease (COPD) with Meta-analysis, and the exposure-effects relationship recommended in the present paper can be applied to the health risk assessment of air pollution in cities. Methods Time-series and case-crossover on the exposure-effects relationship between short-term exposure to particulate matter with aerodynamic diameters less than 10um and 2.5μm (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) and daily hospitalization for COPD were retrieved from PubMed, Medline, Chineses periodical full text database (CNKI), Wanfang database and Vip information database. Based on reviewing full text, the data were selected, evaluated and accessed. RevMan 5.0 software was used to perform the exposure-effects relationship between air pollution and COPD admission. Results A tolal of 11 studies were available for this analysis, including 1,128,241 patients. The Meta-analysis results of exposure-effects relationship between air pollution and COPD admission showed per 10ug/m3 increase in PM2.5, PM10, SO2, NO2, O3 and PM10 concentrations the relative risk estimates increased by 0.05%(95%CI:0.02%~0.13%);0.08%(95%CI: 0.03%~0.27%);0.09%(95%CI:0.03%~0.32%) 0.24%(95%CI:0.21%~0.26%);0.05% (95%CI:0.01%~0.17%)and per 1mg/m3 increase in CO concentrations the relative risk estimates increased by 0.18%(95%CI:0.12%~0.29%). Conclusion We concluded that air pollution were significantly associated with COPD hospitalization. 基金项目 : 吉林大学白求恩医学部医学科研支持计划资助课题 ( ); 吉林省科技发展计划项目 ( JC) 作者简介 : 李春艳 (1987-), 女, 内蒙古锡林浩特市人, 硕士研究生, 主要从事环境与健康关系的研究通信联系人 : 叶琳 (1960-), 女, 吉林省长春市人, 教授, 主要从事环境与健康关系的研究. yel@jlu. edu.cn - 1 -

2 45 Key words: Air pollution; chronic obstructive pulmonary disease (COPD); case-crossover; Time-series; Meta-Analysis 0 引言慢性阻塞性肺疾病 (Chronic obstructive pulmonary disease,copd) 是一种以不完全可逆的气道受限且呈进行性发展为特征的疾病, 多与肺部对有害颗粒及气体的异常炎症反应相关 [1] 据世界卫生组织推测,2030 年 COPD 将成为仅次于缺血性心脏病和脑血管疾病的全球第三大死因 [2] 研究显示大气颗粒物及气态污染物与 COPD 发病和死亡存在显著相关性 [3-5] 目前国内外关于大气污染暴露与 COPD 住院人次关系的研究报道结果不尽相同, 本研究收集国内外已发表的有关大气污染与 COPD 暴露 - 效应关系的文献并进行 Meta- 分析, 系统评价大气污染与居民 COPD 住院人次的暴露 - 效应关系, 为进行大气污染物的危险度评价和疾病归因负担的估计奠定基础, 也为环境决策制定者进一步制定大气污染物限量标准和环保政策提供理论依据 1 材料与方法文献检索通过计算机联机检索, 应用 Endnote 文献检索软件, 对 Pubmed Medline 医学数据库中国期刊全文数据库 (CNKI) 万方数据库和维普数据库等进行文献检索中文检索词为空气污染慢性阻塞性肺疾病 (COPD) 颗粒物 PM2.5/PM10 SO 2 NO 2 O 3 CO 英文检索词为 :(1)air pollution, particles, ambient particulate matter/ PM10/ PM2.5,sulfur dioxide/so 2,nitrogen dioxide/ NO 2,ozone/ O 3,carbon monoxide/ CO;(2)chronic obstructive pulmonary disease/ COPD, emergency hospital admissions/ hospitalizations;(3) time-series, case-crossover, cohort study 并对检出文献的参考文献进行二次检索, 收集国内外公开发表的大气污染与居民 COPD 住院人次关系的文献 1.2 文献纳入标准 (1)2004 年 ~2014 年公开发表的关于大气污染物对居民 COPD 住院影响的流行病学文献, 语言为中文或英文 ;(2)COPD 诊断标准参考国际疾病分类第九次修订版 (ICD-9) 页 ;(3) 研究对象为自然人群 ;(4) 各文献对居民每日 COPD 住院人次与大气污染物水平进行定量的暴露 - 反应关系描述, 且研究数据直接表示或可间接转化 ( 对数线性模型 ) 为大气污染物每升高 10 μg/m 3 或 1mg/m 3, 居民每日 COPD 住院人次增加的百分比 ;(5) 采用的研究方法为病例交叉研究或时间序列研究 ;(6) 采用单污染物模型的研究结果 ;(7) 选取的文献中采用的统计分析模型主要为广义相加模型 (generalized additive model,gam) 和广义线性模型 (generalizedline model,glm) 的时间序列研究 1.3 文献排除标准 (1) 诊断不符合 COPD 诊断要求 ;(2) 数据不完整, 文献中并未提供相对误差及 95%CI 等数据 ; 重复发表 ;(3) 统计方法不恰当的文献 ;(4) 重复发表发表年限较早综述性的文献 1.4Meta- 分析采用 Revman 5.0 软件进行 Meta- 分析对纳入文献进行异质性分析, 选择固定效应或随机效应模型合并效应值统计分析结果以 PM2.5 PM10 SO 2 NO 2 O 3 浓度每上升 10 μg/m 3-2 -

3 85 及 CO 浓度每上升 1mg/m 3 居民 COPD 住院人次上升的百分比 ΔMi 及其 95%CI 来表示, 或用公式 β=ln(or) 转化为效应值 β, 表示为大气污染物浓度每上升 10 μg/m 3 或 1mg/m 3, 居民 COPD 住院人次增加的百分比及其 95%CI 检验水准设定为结果 2.1 纳入文献基本情况根据以上文献纳入和排除标准, 共纳入文献 11 篇, 涉及加拿大台湾香港英国美国五个研究国家及地区, 累计病例 1,128,241 例入选文献的基本情况 ( 见表 1) 表 1 大气污染物对居民 COPD 日入院人次影响的流行病学研究入选文献基本情况 - 3 -

4 第一作者 / 发表时间研究地点 / 时间污染物日平均浓度 ΔMi 95% CI Hong Qiu (2013) [6] 香港, PM ± ( ,-0.050) NO ± (-0.287,0.24) O ± 24.3* ( -0.02,0.385) SO ± (-1.14,0.095) I-Ming Lee 台湾, PM ± (0.142,0.34) (DMT 25 C(2007) [7] NO ± (0.11,0.320) CO 0.77± (0.116,0.23) O ± (0.176,0.295) I-Ming Lee 台湾, PM ± (0.318,0.496) (DMT 25 C(2007) [7] SO ± (0.089,0.258) NO ± (0.579,0.782) CO 0.77± (0.267,0.403) O ± (0.103,0.298) Ko, F. W(2007) [8] 香港, NO 51.2± (0.007,0.014) PM ± (0.008,0.013) O ±16.2* (0.008,0.015) SO ± (0.001,0.014) PM ± (0.010,0.017) Medina-Ramón, M 美国, O ±9.2* (0.0031,0.0066) (DMT 23 C(2006) [9] Medina-Ramón, M 美国, O ±6.3* ( , ) (DMT 23 C(2006) [9] PM ± (0.0030,0.0088) Sauerzapf, V(2009) [10] 英国, CO 0.19± (0.001,0.019) NO ± (0.023,0.22) Tian, L(2014) [11] 香港, PM ± (0.037,0.059) NO ± (0.018,0.038) Tsai, S. S 台湾, PM ± (0.077,0.148) (DMT 23 C(2013) [12] Tsai, S. S ( DMT 23 C ) 台湾, PM ± (0.01,0.067) (2013) [12] WQ Gan(2013) [13] 加拿大, PM ± (0.104,0.174) NO ± (0.113,0.19) Yang C. Y 台湾, PM ± (0.093,0.155) (DMT 20 C(2007) [14] NO ± (0.147,0.207) CO 1.33± (0.164,0.245) O ± (0.111,0.18) Yang C. Y 台湾, SO ± (0.015,0.121) (DMT 20 C(2007) [14] Y Yang, Q (2005) [15] 加拿大, CO 0.71± (0.02,0.122) NO ± (0.04,0.182) PM ± (0.048,0.19) Yue Chen(2004 ) [16] 加拿大, PM ± (0.03,0.140) PM ± (0.017,0.108) - 4 -

5 90 95 注 :1. ΔMi 值表示为 PM2.5 PM10 SO 2 NO 2 O 3 浓度每上升 10 μg/m 3,CO 浓度每上升 1mg/m 3 时居民 COPD 住院人次上升的百分比 ;2. PM2.5 PM10 SO 2 NO 2 CO 为 24h 监测浓度,O 3 为 8h 监测浓度 ; 3. DMT: 日平均温度 2.2 大气污染物对居民 COPD 每日住院人次影响 Meta 分析结果显示,PM2.5 PM10 SO 2 NO 2 O 3 CO 纳入文献的各研究间均存在异质性 (P<0.05), 采用随机效应模型进行估计合并后效应值分别为 0.05%(95%CI: 0.02%~0.13%); 0.08%(95%CI:0.03%~0.27%);0.09%(95%CI:0.03%~0.32%);0.24% (95%CI:0.21%~0.26%); 0.05%(95%CI:0.01%~0.17%);0.18%(95%CI:0.12%~0.29%) 即 PM2.5 PM10 SO 2 NO 2 O 3 每升高 10 μg/m 3,CO 每升高 1mg/m 3 居民 COPD 住院百分比分别上升 0.05% 0.08% 0.09% 0.24% %( 见图 1- 图 6) 100 图 1 PM2.5 每升高 10μg/m 3 对居民 COPD 住院影响的森林图 105 图 2 PM10 每升高 10μg/m 3 对居民 COPD 住院影响的森林图 - 5 -

6 图 3 SO 2 每升高 10μg/m 3 对居民 COPD 住院影响的森林图 110 图 4 NO 2 每升高 10μg/m 3 对居民 COPD 住院影响的森林图图 5 O 3 每升高 10μg/m 3 对居民 COPD 住院影响的森林图 - 6 -

7 115 图 6 CO 每升高 1mg/m 3 对居民 COPD 住院影响的森林图 3 讨论 COPD 发病在发达及发展中国家具有普遍性 [17-18] 研究显示长期暴露于有毒气体和颗粒物与 COPD 疾病进展相关 [19], 但目前并没有充分的评估标准对这一因果关系进行评价 [20] Meta- 分析目的在于增大研究样本含量, 减少误差, 增加研究的检验效能, 可以有效的评价大气污染对居民 COPD 住院的影响本次大气污染物对于居民 COPD 住院影响的定量研究中, 我们纳入 11 篇关于暴露于六种大气污染物 ( 包括 PM2.5 PM10 SO 2 NO 2 O 3 CO) 对居民每日 COPD 住院人次影响的研究, 包括六个时间序列研究及五个病例对照研究 Meta- 分析结果显示, 暴露于大气污染物 PM2.5 PM10 SO 2 NO 2 O 3 CO 与居民 COPD 每日住院人次之间存在明显的相关性其中,PM2.5 PM10 SO 2 NO 2 O 3 每升高 10 μg/m3,co 每升高 1mg/m3 居民 COPD 住院百分比分别上升 0.05%(95%CI:0.02%~0.13%);0.08%(95%CI:0.03%~0.27%); 0.09%(95%CI:0.03%~0.32%);0.24%(95%CI:0.21%~0.26%); 0.05%(95%CI: 0.01%~0.17%),0.18%(95%CI:0.12%~0.29%) 由此可见, 暴露于 PM2.5 PM10 SO 2 NO 2 O 3 和 CO 不同程度增加了居民 COPD 发病风险本研究针对大气污染物暴露对 COPD 发病影响进行了系统性定量评价, 建立的暴露 - 反应关系可以为城市大气污染物健康危险度评价工作提供依据 4 结论 135 大气污染物 PM2.5 PM10 SO 2 NO 2 O 3 CO 的升高不同程度的增加了居民 COPD 每日住院人数, 其中以 NO 2 和 CO 对 COPD 住院影响最为显著 [ 参考文献 ] (References) 140 [1] GOLD Executive Committee. Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease (Revised 2011) [OEB/OL]. www. goldcopd. com, /

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