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

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CRP0.5(2.3)比2(2.5)，P<0.05]、IL-62.3(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。

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

ObjectiveTo 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. MethodsA 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. ResultsThe 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. ConclusionElevated 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.