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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) ›› 2019, Vol. 12 ›› Issue (05) : 544 -549. doi: 10.3877/cma.j.issn.1674-6902.2019.05.002

论著

高原慢性阻塞性肺疾病稳定期血清SP-D水平与肺功能及炎症因子的临床意义
何军頵1, 徐红艳1, 曾以萍1, 邵佳1, 陈杰1, 申永春2, 文富强2,†()   
  1. 1. 610041　成都，西藏自治区人民政府驻成都办事处医院（四川大学华西医院西藏成办分院）　呼吸科
    2. 610041　成都，四川大学华西医院　生物治疗国家重点实验室　呼吸疾病研究室
  • 收稿日期:2019-05-05 出版日期:2019-10-20
  • 通信作者: 文富强
  • 基金资助:
    国家重点研发计划资助项目(No.2016YFC0903600, No.2016YFC1304500)

Clinical significance of serum surfactant protein D level in patients with stable phase of plateau chronic obstructive pulmonary disease and its relationship with pulmonary function and inflammatory factors

Junyun He1, Hongyan Xu1, Yiping Zeng1, Jia Shao1, Jie Cheng1, Yongchun Shen2, Fuqiang Wen2,†()   

  1. 1. Hospital of Chengdu Office of People′s Government of Tibetan Autonomous Region
    2. Department of Medical Informatics, West China Hospital of Sichuan University, Chengdu 610041, China
  • Received:2019-05-05 Published:2019-10-20
  • Corresponding author: Fuqiang Wen
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引用本文：

何军頵, 徐红艳, 曾以萍, 邵佳, 陈杰, 申永春, 文富强. 高原慢性阻塞性肺疾病稳定期血清SP-D水平与肺功能及炎症因子的临床意义[J]. 中华肺部疾病杂志(电子版), 2019, 12(05): 544-549.

Junyun He, Hongyan Xu, Yiping Zeng, Jia Shao, Jie Cheng, Yongchun Shen, Fuqiang Wen. Clinical significance of serum surfactant protein D level in patients with stable phase of plateau chronic obstructive pulmonary disease and its relationship with pulmonary function and inflammatory factors[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2019, 12(05): 544-549.

目的

探讨高原慢性阻塞性肺疾病(COPD)稳定期患者血清肺泡表面活性蛋白D(SP-D)的水平及与肺功能、炎症因子的临床意义。

方法

收集2016年5月至2017年12月在华西医院就诊的世居高原COPD稳定期的患者150例及健康对照组67例，收集两组的临床资料包括年龄、性别、体质指数(BMI)、吸烟指数及肺功能指标，包括FEV1(第1 s用力呼出气容积)、FEV1%(第1 s用力呼出气容积占预计值百分比)、FEV1/FVC%(第1 s用力呼出气容积/用力肺活量比值)，抽取静脉血测定SP-D、CRP(C反应蛋白)、IL-6(白介素6)、TNF-α(肿瘤坏死因子α)。比较两组之间及COPD稳定期的汉、藏族之间的血清SP-D、CRP、IL-6、TNF-α的浓度差异；并将血清SP-D与COPD稳定期患者的肺功能、全身炎症、CAT(COPD测试评分)、mMRC(改良英国医学研究学会呼吸困难指数)作相关性分析；作SP-D在COPD稳定期的多因素回归分析，并作SP-D在COPD稳定期的ROC分析。

结果

COPD稳定组的SP-D高于对照组[(12 524±8 796)vs.(9 288±5 640 ng/L)，P<0.05]、COPD稳定组的炎症指标如CRP[0.5(2.3)比2(2.5)，P<0.05]、IL-6[2.3(2.2)vs. 1.1(1.4)，P<0.05]、TNF-α[(5.5±2.7)vs.(7.8±6.7)，P<0.05]，均显著高于对照组。COPD稳定组的SP-D与CAT、mMRC评分呈正相关(r＝0.498，P<0.05；r＝0.512，P<0.05)，与炎症因子CRP、IL-6、TNF-α的水平呈正相关(r＝0.369，P<0.05；r＝0.454，P<0.05；r＝0.529，P<0.05)，与肺功能指标FEV1%、FEV1/FVC%呈负相关(r＝-0.404，P<0.05；r＝-0.171，P<0.05)。对COPD稳定期患者，汉、藏族在血清SP-D及炎症因子CRP、IL-6、TNF-α之间的浓度水平均无统计学差异(P>0.05)。对SP-D在COPD稳定期的多因素回归分析，没有发现与稳定期相关的指标，均P>0.05。在ROC统计中，SP-D的阈值为9 303.5，敏感度为0.576，特异度为0.616，SP-D对诊断COPD稳定期有一定诊断价值。

结论

血清SP-D升高可反应全身炎症水平，有助于评估高原COPD患者的肺功能程度及病情变化。对高原COPD病情的预测与评估有一定临床意义。

关键词: 高原, COPD稳定期, 肺泡表面活性蛋白D, 肺功能, 全身炎症反应
Objective

To investigate the serum level of surfactant protein D (SP-D) in the patients with stable phase of plateau chronic obstructive pulmonary disease (COPD) and its relationship with frequent exacerbator phenotype, lung function, and systemic inflammation.

Methods

A total of 150 patients living on plateau for generations with stable COPD hospitalized in West China Hospital of Sichuan University from May 2016 to December 2017 (the COPD group) and 67 healthy controls (the control group) were enrolled in this study. The clinical data of the two groups were collected including their age, gender, body mass index (BMI), the smoking index and the lung function indicators including the forced expiratory volume in one second (FEV1), FEV1%, FEV1/the forced vital capacity (FVC)%. Venous blood was taken to measure the SP-D, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factorα (TNF-α). The differences in the serum SP-D, CRP, IL-6, and TNF-α were analyzed between the Han and Tibetans in the stable phase of COPD and between the two groups. Correlation analyses were made between the serum SP-D and pulmonary function and systemic inflammation, CAT (COPD testing scores) and modified British Medical Research Council (mMRC) scores in the patients with stable COPD. Statistical multivariate regression analysis was made for the SP-D of the patients in the stable phase of COPD and its relationship with the Han and Tibetans. In ROC analysis, P<0.05 was considered as statistical significance.

Results

The SP-D of the COPD group was higher than that of the control group (12 524±8 796 vs. 9 288±5 640 ng/L, P<0.05), The inflammation indexes, such as CRP [0.5 (2.3) in the COPD group vs. 2 (2.5) in the control group, P<0.05], IL-6 [2.3(2.2) in the COPD group vs. 1.1(1.4) in the control group, P<0.05], and TNF-α(5.5±2.7 in the COPD group vs. 7.8±6.7 in the control group, P<0.05) had significant differences between the two groups. The SP-D of the COPD group was positively correlated with the CAT score (r=0.498, P<0.05), mMRC score (r=0.512, P<0.05), and the levels of inflammatory factors such as CRP (r=0.369, P<0.05), IL-6 (r=0.454, P<0.05) and TNF-α (r=0.529, P<0.05), and negatively correlated with the lung function indexes such as FEV1% (r=-0.404, P<0.05) and FEV1/FVC% (r=-0.171, P<0.05). There was no significant difference in serum SP-D and inflammatory factors of CRP, IL-6 and TNF-α between the Han and Tibetan patients in the stable COPD patients (P>0.05). The multivariate regression analysis showed that P>0.05 was found in the SP-D of the COPD patients, but no indicator related to the stable phase was found. In the ROC statistics, the threshold of SP-D was 9 303.5, the sensitivity was 0.576, and the specificity was 0.616. SP-D had certain diagnostic values for the diagnosis of COPD in the stable phase.

Conclusion

Elevated serum SP-D can reflect the systemic inflammatory levels, is helpful to assess the degree of pulmonary function, and diseases the changes in the patients with high-altitude COPD. It has a certain effect on the prediction and evaluation of plateau COPD.

Key words: Plateau, Chronic obstructive pulmonary disease, Surfactant protein D, Lung functions, Systemic inflammation
表1 COPD患者临床一般资料比较
临床资料 对照组(n＝67) 稳定组(n＝150) P值
年龄(岁，±s) 47.2±12.7 64.3±10.1 <0.001
性别[n(%)] 男 46(68.7) 107(71.3) 0.069
  女 21(31.3) 43(28.7)  
民族[n(%)] 汉 26(38.8) 56(37.3) 0.063
  藏 41(61.2) 94(62.7)  
BMI(kg/m2，±s) 24.6±3.7 23.2±4.2 0.024
吸烟指数(包/年) 380 740 <0.001
平素CAT评分(分，±s) 3.0±1.7 14.6±6.8 <0.001
平素mMRC评分(分，±s) 0.8±0.5 1.3±1.1 0.002
FEV1(L，±s) 2.9±0.8 1.4±0.7 <0.001
FEV1%预计值(%，±s) 99.3±19.1 55.0±21.6 <0.001
FEV1/FVC(%，±s) 85.7±7.0 57.1±17.2 <0.001
TNF-α(ng/L，±s) 5.5±2.7 7.8±6.7 0.018
SP-D(ng/L，±s) 9 288±5 640 12 524±8 796 0.012
CRP(mg/L，M(Q)) 0.5(2.3) 2(2.5) <0.001
IL-6(ng/L，M(Q)) 2.3(2.2) 1.1(1.4) <0.001
图1 COPD患者血清SP-D与FEV1%的关系
图2 COPD患者血清SP-D与CRP的关系
图3 COPD患者血清SP-D与TNF-α的关系
图4 COPD患者血清SP-D与CAT的关系
图5 COPD患者血清SP-D与mMRC的关系
表2 SP-D在COPD稳定期的多因素回归分析
临床资料 β P值
年龄 2.717 0.976
BMI -9.371 0.973
CAT评分 8.610 0.973
mMRC评分 -28.035 0.981
FEV1 8.852 0.994
FEV1% -2.133 0.973
FEV1/FVC -2.316 0.979
CRP -2.379 0.996
IL-6 1.068 0.989
TNF-α -20.321 0.974
SPD -0.001 0.996
表3 SP-D在诊断COPD稳定期的ROC分析结果
面积 标准误 P值 95%CI 阈值 敏感度 特异度 约登指数
0.604 0.040 0.012 0.526～0.681 9 303.500 0.576 0.616 0.193
图6 SP-D诊断COPD稳定期的ROC分析
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