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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2025, Vol. 18 ›› Issue (05) : 702 -707. doi: 10.3877/cma.j.issn.1674-6902.2025.05.007

论著

中性粒细胞-白蛋白比值对慢性阻塞性肺疾病危重患者全因死亡风险的预测意义
周滇妹, 字楷, 文富强†()   
  1. 610041　成都，四川大学华西医院呼吸与危重症医学科
  • 收稿日期:2025-06-09 出版日期:2025-10-25
  • 通信作者: 文富强

Neutrophil percentage to albumin ratio as a predictor of all-cause mortality in critically ill patients with chronic obstructive pulmonary disease

Dianmei Zhou, Kai Zi, Fuqiang Wen†()   

  1. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
  • Received:2025-06-09 Published:2025-10-25
  • Corresponding author: Fuqiang Wen
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周滇妹, 字楷, 文富强. 中性粒细胞-白蛋白比值对慢性阻塞性肺疾病危重患者全因死亡风险的预测意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 702-707.

Dianmei Zhou, Kai Zi, Fuqiang Wen. Neutrophil percentage to albumin ratio as a predictor of all-cause mortality in critically ill patients with chronic obstructive pulmonary disease[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(05): 702-707.

目的

探讨中性粒细胞-白蛋白比值(neutrophil percentage to albumin ratio, NPAR)对慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)危重患者短期(28 d)及长期(365 d)全因死亡风险的预测价值。

方法

基于美国重症监护医学信息数据库(Medical Information Mart for Intensive Care Ⅳ，MIMIC-Ⅳ)，采用回顾性队列研究设计，纳入539例接受重症监护的COPD患者。根据NPAR四分位数将患者分为Q1~Q4组，主要研究终点为28 d及365 d全因病死率。采用Kaplan-Meier法绘制生存曲线并进行log-rank检验；通过单因素及多因素Cox比例风险回归模型分析NPAR与死亡风险的相关性。利用限制性立方样条(restricted cubic spline, RCS)分析NPAR与死亡风险的剂量-反应关系，若存在非线性关联，则采用两段线性回归模型确定关联转折点。通过亚组分析检验结果的稳健性。

结果

研究人群的中位年龄为71岁(63~79)，男性281例(52.1%)。生存分析显示，Q4组患者28 d及365 d累积生存率显著低于其他组别(log-rank检验，P<0.001)。经多因素校正后，Q4组患者28 d死亡风险[校正风险比(adjusted hazard ratio, aHR)＝1.61，95%CI：1.06~2.43，P＝0.024]及365 d死亡风险(aHR＝1.87，95%CI：1.32~2.65，P<0.001)显著高于Q1组。RCS分析显示NPAR与死亡率呈非线性U型关联(非线性检验P<0.001)，转折点分别为22.88 d(28 d)和22.29 d(365 d)。超过转折点后，NPAR每增加1个单位，28 d死亡风险增加4.4%(HR＝1.044，95%CI：1.027~1.062，P<0.001)，365 d死亡风险增加3.8%(HR＝1.038，95%CI：1.022~1.054，P<0.001)。亚组分析未发现显著交互作用(交互作用P>0.05)。

结论

NPAR是COPD危重患者短期及长期死亡风险的预测指标，其U型剂量-反应关系为临床风险分层和预后评估提供了新的量化依据。

关键词: 肺疾病，慢性阻塞性, 中性粒细胞-白蛋白比值, 死亡风险
Objective

To investigate the predictive value of the neutrophil percentage to albumin ratio (NPAR) for short-term 28 day and long-term 365 day all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD).

Methods

Using a retrospective cohort design based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ) database, we enrolled 539 COPD patients admitted to the intensive care unit (ICU). Patients were stratified into quartiles (Q1~Q4) according to NPAR levels. The primary endpoints were 28 day and 365 day all-cause mortality. Kaplan-Meier survival curves were constructed, and differences were assessed using the log-rank test. Univariate and multivariate Cox proportional hazards regression models were employed to evaluate the association between NPAR and mortality. Restricted cubic spline (RCS) analysis was used to examine the dose-response relationship; if a nonlinear association was detected, a two-piecewise linear regression model was applied to identify the inflection point. Subgroup analyses were performed to assess the robustness of the findings.

Results

The median age of the study population was 71 (63-79) years, with 281 (52.1%) male patients. Kaplan-Meier analysis revealed that the Q4 group had significantly lower cumulative survival rates at both 28 and 365 days compared to other groups (log-rank test, allP<0.001). After multivariate adjustment, the Q4 group exhibited significantly higher risks of 28-day mortality [adjusted hazard ratio (aHR)=1.61, 95%CI: 1.06~2.43, P=0.024] and 365-day mortality (aHR=1.87, 95%CI: 1.32~2.65, P<0.001) compared to the Q1 group. RCS analysis demonstrated a nonlinear U-shaped association between NPAR and mortality (nonlinearity P<0.001), with inflection points at 22.88 28 day and 22.29 365 day. Beyond these thresholds, each 1-unit increase in NPAR was associated with a 4.4% increase in 28 day mortality risk (HR=1.044, 95%CI: 1.027~1.062, P<0.001) and a 3.8% increase in 365 day mortality risk (HR=1.038, 95%CI: 1.022~1.054, P<0.001). Subgroup analyses showed no significant interaction effects (all interaction P>0.05).

Conclusion

NPAR is an independent predictor of short-and long-term all-cause mortality in critically ill COPD patients. The U-shaped dose-response relationship provides a novel quantitative basis for clinical risk stratification and prognostic assessment.

Key words: Chronic obstructive pulmonary disease, Neutrophil percentage to albumin ratio, Mortality
表1 按NPAR四分位数分组患者的临床特征比较
临床资料 总体(n＝539) Q1(n＝136) Q2(n＝136) Q3(n＝132) Q4(n＝135) P值
体质量(kg) 80.0(66.0, 94.6) 80.4(65.8, 93.2) 84.5(69.1, 95.9) 80.7(68.0, 96.7) 74.6(61.2, 89.6) 0.031
CCI 6(5, 9) 6(5, 8) 7(5, 9) 7(5, 9) 6(5, 9) 0.488
高血压[n(%)] 122(22.6) 30(22.1) 32(23.5) 26(19.7) 34(25.2) 0.743
糖尿病[n(%)] 175(32.5) 45(33.1) 48(35.3) 50(37.9) 32(23.7) 0.072
心肌梗死[n(%)] 133(24.7) 35(25.7) 40(29.4) 33(25.0) 25(18.5) 0.214
心力衰竭[n(%)] 240(44.5) 57(41.9) 74(54.4) 57(43.2) 52(38.5) 0.050
轻度肝病[n(%)] 104(19.3) 34(25.0) 22(16.2) 27(20.5) 21(15.6) 0.170
重度肝病[n(%)] 50(9.3) 15(11.0) 11(8.1) 11(8.3) 13(9.6) 0.829
肾脏疾病[n(%)] 139(25.8) 28(20.6) 41(30.1) 37 (28.0) 33(24.4) 0.290
恶性肿瘤[n(%)] 89(16.5) 16(11.8) 17(12.5) 27(20.5) 29(21.5) 0.052
APSⅢ 52(40, 66) 46(36, 63) 47(36, 60) 55(43, 67) 61(49, 79) 0.001
SAPSⅡ 42(34, 52) 39(29, 50) 38(33, 48) 44(37, 54) 48(39, 55) 0.001
SOFA 6(4, 9) 6(3, 8) 5(3, 8) 7(4, 9) 7(4, 11) 0.001
心率(次/min) 88(76, 100) 85(75, 98) 88(76, 99) 91(78, 102) 87(78, 102) 0.205
呼吸(次/min) 20(18, 23) 20(17, 22) 20(18, 22) 20(18, 23) 20(18, 24) 0.589
平均动脉压(mmHg) 75(69, 82) 76(72, 85) 76(69, 84) 74(69, 80) 72(67, 78) 0.001
脉氧饱和度(%) 96(95, 98) 96(95, 98) 96(95, 97) 96(95, 98) 96(94, 98) 0.478
血红蛋白(g/dl) 10.5(8.9, 12.1) 11.3(9.4，12.5) 11.0(9.3, 12.2) 10.4(8.9, 12.0) 9.7(8.5, 11.0) 0.001
血小板(109/L) 193(130, 262) 179(121, 227) 211(150, 282) 189(131, 264) 192(125, 289) 0.013
白细胞(109/L) 12.0(8.2, 17.2) 9.7(6.6，13.5) 11.7(8.0, 15.0) 12.6(9.1, 18.0) 14.6(10.0, 20.5) 0.001
中性粒细胞(109/L) 9.89(6.30，14.63) 6.90(4.66，10.87) 9.46(6.51，13.15) 10.70(7.32，16.33) 13.43(8.45，18.26) 0.001
白蛋白(g/dl) 3.1(2.6, 3.5) 3.6(3.2, 3.90) 3.4(3.1, 3.6) 3.0(2.7, 3.2) 2.4(2.1, 2.6) 0.001
血糖(mg/dl) 132(104, 177) 122(102, 148) 144(113, 182) 140(104, 182) 132(100, 174) 0.005
肌酐(mg/dl) 1.2(0.8, 1.9) 1.1(0.8, 1.7) 1.1(0.8, 1.9) 1.4(0.8, 2.1) 1.2(0.8, 1.9) 0.174
钙(mmol/L) 8.1(7.5, 8.8) 8.5(8.0, 9.1) 8.5(7.9, 8.9) 8.0(7.5, 8.7) 7.6(7.1, 8.1) 0.001
钾(mmol/L) 4.2(3.7, 4.7) 4.2(3.8, 4.7) 4.3(3.9, 4.9) 4.3(3.7, 4.7) 4.0(3.6, 4.4) 0.002
PT (s) 14.3(12.5, 17.6) 13.3(11.9, 16.5) 13.6(12.2, 17.3) 14.7(12.6, 17.8) 15.4(13.7, 18.3) 0.001
APTT(s) 31.2(27.9, 39.1) 30.4(27.6, 36.9) 30.1(27.9, 38.2) 31.6(27.9, 40.3) 32.3(28.8, 41.2) 0.212
ICU时长(d) 4(2, 8) 4(2, 8) 4(2, 8) 4(2, 8) 4(3, 8) 0.609
住院时长(d) 9(6, 17) 9(5, 18) 9(6, 14) 10(6, 17) 11(6, 18) 0.303
院内死亡[n(%)] 133(24.7) 29(21.3) 23(16.9) 34(25.8) 47(34.8) 0.005
28 d死亡[n(%)] 182(33.8) 36(26.5) 35(25.7) 47(35.6) 64(47.4) 0.001
90 d死亡[n(%)] 204(37.8) 40(29.4) 39(28.7) 54(40.9) 71(52.6) 0.001
365 d死亡[n(%)] 272(50.5) 51(37.5) 62(45.6) 71(53.8) 88(65.2) 0.001
表2 28 d全因病死率的Cox比例风险回归分析
组　别 模型1 模型2
HR(95%CI) P值 aHR(95%CI) P值
Q1 1.00(参考)   1.00(参考)  
Q2 0.95(0.60，1.51) 0.825 0.88(0.55，1.41) 0.603
Q3 1.40(0.91，2.16) 0.127 1.11(0.71，1.71) 0.654
Q4 2.06(1.37，3.10) 0.001 1.61(1.06，2.43) 0.024
表3 365 d全因病死率的Cox比例风险回归分析
组　别 模型1 模型2
HR(95%CI) P值 HR(95%CI) P值
Q1 1.00(参考)   1.00(参考)  
Q2 1.20(0.83，1.74) 0.330 1.14(0.78，1.65) 0.498
Q3 1.58(1.10，2.27) 0.013 1.31(0.91，1.89) 0.140
Q4 2.23(1.58，3.15) 0.001 1.87(1.32，2.65) 0.001
图1 NPAR与28 d(A)及365 d(B)全因病死率的限制性立方样条回归分析
表4 NPAR与28 d及365 d全因病死率关联的亚组分析
临床资料及亚组 28 d全因病死率 365 d全因病死率
[n(%)] HR(95%CI) P值 交互效应P值 [n(%)] HR(95%CI) P值 交互效应P值
性别       0.551       0.625
男 281(52.1) 1.04(1.02，1.07) 0.001   281(52.1) 1.04(1.02，1.06) 0.001  
女 258(47.9) 1.03(1.01，1.05) 0.003   258(47.9) 1.03(1.01，1.05) 0.001  
种族       0.314       0.893
白种人 352(65.3) 1.04(1.02，1.06) 0.001   352(65.3) 1.04(1.02，1.06) 0.001  
其他 187(34.7) 1.03(1.00，1.05) 0.051   187(34.7) 1.03(1.01，1.05) 0.003  
高血压 122(22.6) 1.06(1.03，1.09) 0.001 0.095 122(22.6) 1.05(1.03，1.08) 0.001 0.179
糖尿病 175(32.5) 1.03(0.99，1.06) 0.110 0.680 175(32.5) 1.02(0.99，1.05) 0.167 0.257
心肌梗死 133(24.7) 1.03(1.00，1.07) 0.060 0.753 133(24.7) 1.03(1.00，1.06) 0.037 0.591
心力衰竭 240(44.5) 1.04(1.01，1.06) 0.008 0.970 240(44.5) 1.03(1.01，1.05) 0.015 0.443
轻度肝脏疾病 104(19.3) 1.03(0.98，1.08) 0.217 0.692 104(19.3) 1.03(0.99，1.07) 0.114 0.798
重度肝脏疾病 50(9.3) 1.02(0.98，1.08) 0.338 0.566 50(9.3) 1.03(0.99，1.07) 0.168 0.754
肾脏疾病 139(25.8) 1.02(0.99，1.06) 0.128 0.453 139(25.8) 1.02(1.00，1.05) 0.093 0.339
恶性肿瘤 89(16.5) 1.01(0.97，1.04) 0.772 0.062 89(16.5) 1.01(0.98，1.04) 0.577 0.065
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