The risk factors for death in chronic obstructive pulmonary disease patients: a systematic review and Meta-analysis of cohort studies
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摘要:
目的 系统评价慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)患者死亡危险因素。 方法 检索PubMed、Cochrane Library、Web of Science、Embase、中国知网、维普网、万方数据知识服务平台和中国生物医学文献数据库有关COPD患者死亡危险因素的研究，再筛选文献、提取数据和质量评价，并进行荟萃分析。 结果 纳入15篇队列研究，纽卡斯尔-渥太华(Newcastle-Ottawa Scale, NOS)量表评分7~9分。荟萃分析结果显示：高龄(HR=1.074, 95% CI: 1.048~1.101, P＜0.001)、吸烟(HR=1.390, 95% CI: 1.298~1.490, P＜0.001)、低BMI(HR=1.434, 95% CI: 1.190~1.727, P＜0.001)、高改良英国医学研究学会呼吸困难指数(modified British medical research council, mMRC)(HR=1.597, 95% CI: 1.550~1.646, P＜0.001)、高Charlson共病指数(Charlson comorbidity index, CCI)(HR=1.191, 95% CI: 1.096~1.294, P＜0.001)、Ⅳ级COPD(HR=2.114, 95% CI: 1.681~2.658, P＜0.001)与COPD患者死亡关联有统计学意义。女性(HR=1.091, 95% CI: 0.781~1.522, P=0.610)、低去脂体重指数(fat free mass index, FFMI)(HR=3.025, 95% CI: 0.268~34.203, P=0.371)与COPD患者死亡关联无统计学意义。描述性分析结果显示高N端脑钠肽前体(N-terminal pro-brain nitric peptide, NT-proBNP)、铜绿假单孢菌(pseudomonas aeruginosa, PA)阳性可能是COPD患者死亡的危险因素。 结论 高龄、吸烟、低BMI、高mMRC、高CCI、Ⅳ级COPD是COPD患者死亡的独立危险因素，女性和低FFMI不是COPD患者死亡的危险因素，高NT-proBNP、PA感染与COPD患者的死亡关系还需进一步研究证明。 Abstract:Objective To systematically review the risk factors for death in chronic obstructive pulmonary disease (COPD) patients. Methods PubMed, Cochrane Library, Web of Science, Embase, CNKI, CBM, VIP and WanFang databases were searched to query the original studies. Then two researchers further screened the studies simultaneously, extracted the data and assessed study quality, and performed Meta-analysis. Results A total of 15 studies were included with Newcastle-Ottawa Scale (NOS) score were among 7 to 9. Meta-analysis showed that elderly people (HR=1.074, 95% CI: 1.048-1.101, P < 0.001), had a high Charlson comorbidity index (CCI) score (HR=1.191, 95% CI: 1.096-1.294, P < 0.001), low BMI (HR=1.434, 95% CI: 1.190-1.727, P < 0.001), smoking (HR=1.390, 95% CI: 1.298-1.490, P < 0.001), had a high modified British medical research council (mMRC) score (HR=1.597, 95% CI: 1.550-1.646, P < 0.001), had Ⅳ COPD (HR=2.114, 95% CI: 1.681-2.658, P < 0.001) were related to the mortality in COPD patients. There was no statistically significant difference between women (HR=1.091, 95% CI: 0.781-1.522, P=0.610), low fat free mass index (FFMI) (HR=3.025, 95% CI: 0.268-34.203, P=0.371) and COPD mortality. Descriptive analysis results showed that high N-terminal pro-brain nitric peptide (NT-proBNP), positive pseudomonas aeruginosa (PA) might be involved in the deaths of COPD patients. Conclusions Among COPD patients, those with advanced age, low BMI, had high CCI and mMRC index score, smoking and those with ⅣCOPO were more likly to have mortality outcomes. And the relationship between high NT-proBNP, PA infection and the mortality in COPD patients still needed further research. -
Key words:
- Chronic obstructive pulmonary disease /
- Death /
- Risk factors /
- Cohort studies /
- Systematic review
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图 3 CCI与COPD患者死亡关系的森林图
Figure 3. Forest map of the relationship between CCI and the mortality in COPD patients
表 1 纳入研究基本特征
Table 1. Basic characteristics about the literatures
纳入研究及发表年份(年) 国家 数据来源 样本量(n) 男/女(n) 年龄(岁) 随访时间(年) 暴露因素 校正因素 Marco等[10]，2019 西班牙 单中心 118 95/23 66.6±9.0 2.00 D、H 年龄、梗阻严重程度 de Blasio等[11]，2019 意大利 单中心 210 143/67 — 2.00 H 年龄、性别、6 min步行距离 Ho等[12]，2016 中国 单中心 104 98/6 74.2±6.9 3.00 A、D、E 年龄、性别、BMI Martínez-García等[13]，2013 西班牙 多中心 201 182/19 70.3±8.9 0.50 A、C、F、H BMI、加重次数 吕志强等[14]，2011 中国 单中心 352 287/65 75.0 1.00 C 年龄、性别 Eklöf等[15]，2020 丹麦 多中心 22 053 9 868/12 185 69.0 3.00 A、D、E、F 年龄、性别、吸烟 Holmgaard等[16]，2013 丹麦 单中心 462 230/232 — 3.00 A、C、D、F、G 年龄、性别、第1 s用力呼气容积 Brekke等[17]，2008 挪威 单中心 897 441/456 70.9 2.00 A、B、D 年龄、性别 Morasert等[18]，2020 泰国 单中心 358 309/49 — 住院期间 A COPD急性加重期、体温、平均动脉压 Oh等[19]，2018 韩国 多中心 629 615/14 — 2.00 A、B、D、F 年龄、性别、BMI Zhang等[20]，2020 中国 单中心 829 588/241 — 5.00 A、C 年龄、Charlson综合症 Høiseth等[21]，2012 挪威 单中心 99 52/47 71.5±9.0 2.00 A、B BMI、糖尿病、C反应蛋白 Holmgaard等[22]，2013 丹麦 单中心 460 — — 5.00 A、B、C、G 年龄、性别、COPD分期 Prudente等[23]，2018 巴西 单中心 133 92/41 — 3.00 A、C 年龄、性别、血氧饱和度 Mao等[24]，2020 中国 单中心 488 340/148 77.0 0.25 A C反应蛋白、呼吸衰竭 注：暴露因素：A：高龄；B：女性；C：高Charlson合并症指数(Charlson comorbidity index, CCI)；D：BMI；E：吸烟；F：高改良英国医学研究学会呼吸困难指数(modified British medical research council, mMRC)；G：Ⅳ级COPD；H：低去脂体重指数(fat free mass index, FFMI)。 
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表 2 纳入研究质量评价
Table 2. Quality evaluation about the literatures
纳入研究 人群选择(分) 组间可比性(分) 结果测量(分) 总分(分) (1) (2) (3) (4) (5) (6) (7) (8) Marco等[10] 1 1 1 1 2 1 1 1 9 de Blasio等[11] 1 0 1 1 2 1 1 1 8 Ho等[12] 1 1 1 1 2 1 1 1 9 Martínez-García等[13] 1 1 1 1 2 1 1 0 8 吕志强等[14] 1 1 1 1 2 1 1 1 9 Eklöf等[15] 1 1 1 1 2 1 1 1 9 Holmgaard等[16] 1 1 1 1 2 1 0 0 7 Brekke等[17] 1 1 1 1 2 1 1 0 8 Morasert等[18] 1 1 1 1 2 1 1 1 9 Oh等[19] 1 1 1 1 2 1 1 0 8 Zhang等[20] 1 1 1 1 2 1 1 1 9 Høiseth等[21] 1 1 1 1 2 1 1 0 8 Holmgaard等[22] 1 1 1 1 2 1 1 1 9 Prudente等[23] 1 1 1 1 2 1 1 1 9 Mao等[24] 1 1 1 1 2 1 1 1 9 注：(1)病例定义与诊断是否准确；(2)病例代表性；(3)对照的选择；(4)对照定义；(5)病例和对照组可比性；(6)暴露的调查和评估；(7)病例和对照的调查；(8)应答率。
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表 3 COPD患者死亡危险因素荟萃分析结果
Table 3. The result of Meta-analysis of the risk factors for mortality in the COPD patients
危险因素 纳入研究数(n) 异质检验结果 效应模型 荟萃分析结果 I2值 P值 HR(95%CI)值 P值 高龄 12[13-14, 16-25] 86.9% ＜0.001 随机效应模型 1.074(1.048~1.101) ＜0.001 女性 4[17, 20, 22-23] 63.5% 0.041 随机效应模型 1.091(0.781~1.522) 0.610 吸烟 3[13, 16-17] 0.0% 0.752 固定效应模型 1.390(1.298~1.490) ＜0.001 低BMI 4[11, 13, 17-18] 0.0% 0.448 固定效应模型 1.434(1.190~1.727) ＜0.001 高mMRC 3[14, 16, 20] 0.0% 0.702 固定效应模型 1.597(1.550~1.646) ＜0.001 高CCI 5[14, 17, 21, 23-24] 0.0% 0.602 固定效应模型 1.191(1.096~1.294) ＜0.001 Ⅳ级COPD 2[17, 23] 0.0% 0.762 固定效应模型 2.114(1.681~2.658) ＜0.001 低FFMI 2[11-12] 81.5% 0.020 随机效应模型 3.025(0.268~34.203) 0.371
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表 4 转换效应模型分析与发表偏倚结果
Table 4. Transformation effect model analysis and publication bias results
危险因素 效应模型HR(95%CI)值 Egger’s检验结果 固定效应模型 随机效应模型 t值 P值 高龄 1.058(1.054~1.063) 1.074(1.048~1.101) 1.45 0.177 女性 0.992(0.847~1.163) 1.091(0.781~1.522) 0.74 0.536 吸烟 1.390(1.298~1.490) 1.390(1.298~1.490) -0.33 0.796 低BMI 1.434(1.190~1.727) 1.434(1.190~1.727) 1.73 0.226 高mMRC 1.597(1.550~1.646) 1.597(1.550~1.646) -6.43 0.098 高CCI 1.191(1.096~1.294) 1.191(1.096~1.294) 2.32 0.103 Ⅳ级COPD 2.040(1.681~2.658) 2.040(1.681~2.658) — — 低FFMI 1.222(0.749~1.991) 3.025(0.268~34.203) — —
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