慢阻肺急性加重患者外周血单核细胞CD64，TLR2及TLR4水平表达与预后的关系研究

目的　研究慢阻肺急性加重（AECOPD）患者外周血单核细胞CD64和Toll样受体2(TLR2)和Toll样受体4(TLR4)与预后的关系。方法　将南京医科大学附属江苏盛泽医院2017.06~2020.06间收治的96例慢阻肺急性加重（AECOPD）患者纳为研究对象，同时将30例稳定期COPD患者纳为稳定组，30例健康志愿者纳为对照组。采集三组外周静脉血，检测单核细胞亚群CD64，TLR2和TLR4的表达水平，分析其与炎症标志物降钙素原（PCT）、白细胞介素-6（IL-6）、白细胞计数（WBC）及肺功能间的相关性，随访6个月，统计AECOPD组中再次急性复发的患者，绘制受试者特征工作曲线（ROC），分析外周血单核细胞亚群CD64表达，TLR2和TLR4在AECOPD急性复发中的预测价值。结果　COPD组以及AECOPD组外周血CD64水平（32.69±6.43，39.69±7.79 vs 26.74±5.14），TLR2水平（169.79±29.07，181.15±22.44 vs 140.03±28.74）以及TLR4水平（186.25±34.15，200.58±33.47 vs 153.65±35.14）均高于对照组，差异均有统计学意义（F=51.774，26.957，2.488，均P<0.05），AECOPD组外周血CD64，TLR2以及TLR4水平均高于COPD组，差异具有统计学意义（t=4.466，2.249，2.037，均P<0.05）；随访6个月，96例AECOPD患者中共20例患者因再次急性复发入院，再次复发者首次入院时外周血TLR2（249.66±40.52 vs 163.21±35.64）、TLR4（253.66±36.85 vs 186.69±45.21）及CD64（53.69±13.58 vs 35.41±14.47）水平均高于无复发者，差异均有统计学意义（t=9.379，6.105，5.089，均P=0.000）。相关性分析提示，AECOPD患者外周血CD64与其吸烟史，IL-6，PCT水平呈正相关（r=0.36，0.33，0.31,均P<0.05），与FEV1/FVC呈负相关（r=-0.45, P<0.05）。TLR2与其PCT水平呈正相关（r=0.34, P<0.05），与FEV1/FVC呈负相关（r=-0.35, P<0.05），TLR4与其他临床指标无相关性（r=0.07，0.11，0.13，0.13，-0.17，-0.23，-0.26，0.29, 均P >0.05）。绘制ROC曲线发现，血清CD64，TLR2及TLR4在预测AECOPD患者再次急性复发中均具有良好的应用效能，各指标单独应用时以TLR2应用效能最高，其AUC=0.805，95%CI(0.679~0.931)，三指标联合应用的预测效能最高，AUC=0.833，95%CI(0.703~0.964)。结论　AECOPD患者外周血CD64，TLR2及TLR4水平均较COPD者明显升高，且其在预测患者半年内再次急性复发中具有良好的效能。

Relationship between the Expression of CD64,TLR2 and TLR4 Levels in Peripheral Blood Monocytes in Patients with Acute Aggravation of COPD

Objective　To study the relationship of peripheral blood mononuclear cell subsets CD64, Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR2) expressions with the prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods　96 cases of AECOPD, 30 cases of stable COPD and 30 healthy individuals in Jiangsu Shengze Hospital Affiliated to Nanjing Medical University from June 2017 to June 2020 wereenrolled, and set as AECOPD group, COPD group and control group, respectively. Peripheral venous blood of three groups was collected, and the expression levels of monocyte subsets CD64, TLR2 and TLR4 were measured, thereafter their correlation with inflammatory markers procalcitonin (PCT), interleukin-6 (IL-6), white blood cell count (WBC) and lung function was discussed. All patients completed a six-month follow-up. The acute recurrence rate of AECOPD was recorded. Then receiver operating characteristic (ROC) curve was used to evaluate the predictive value of peripheral blood monocyte subsets CD64, TLR2 and TLR4 in acute recurrence of AECOPD. Results　Compared with control group, COPD group and AECOPD group had significantly higher levels of peripheral blood CD64 (32.69±6.43, 39.69±7.79 vs 26.74±5.14), TLR2 (169.79±29.07, 181.15±22.44 vs 140.03±28.74) and TLR4 (186.25± 34.15, 200.58±33.47 vs 153.65±35.14), the differences were statistically significant (F=51.774，26.957，2.488, all P<0.05). Compared with COPD group, AECOPD group had significantly higher levels of peripheral blood CD64, TLR2 and TLR4, the differences were statistically significant (t=4.466, -2.249, -2.037, all P<0.05). During the six-month follow-up period, a total of 20 of the 96 patients with AECOPD were admitted to hospital for a second acute relapse. Compared with those without recurrent, patients with acute recurrent had significantly higher levels of peripheral blood TLR2 (249.66±40.52 vs 163.21±35.64) and TLR4 (253.66±36.85 vs 186.69±45.21), CD64 (53.69±13.58 vs 35.41±14.47), the differences were statistically significant (t=-9.379, -6.105, 5.089, all P=0.000). Correlation analysis showed that CD64 was positively correlated with smoking history (t=0.36, P<0.05), PCT (r=0.31, P<0.05) and IL-6 (r=0.33, P<0.05) levels in peripheral blood of AECOPD patients, and negatively correlated with forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) of AECOPD patients (r=-0.45, P<0.05); TLR2 was positively correlated with PCT levels (r=0.34, P<0.05), and negatively correlated with FEV1/FVC (r=-0.35, P<0.05). TLR4 showed no clinical correlation with other indexes (r=-0.07, -0.11, 0.13, -0.13, -0.17, -0.23,-0.26,-0.29, all P>0.05). ROC curve of three indicators found that TLR2 had the highest efficacy in predicting the acute recurrence of AECOPD [AUC=0.805, 95%CI (0.679~0.931)], meanwhile, the combined detection of three indicators had significantly higher predictive efficacy for acute recurrence than that of the single detection [AUC=0.833, 95%CI (0.703~0.964)]. Conclusion　Peripheral blood levels of CD64, TLR2 and TLR4 are significantly elevated in patients with AECOPD compared to those with COPD patients, and all three indicators have good efficacy in predicting acute recurrence within six months.