YKL-40水平预测慢性阻塞性肺疾病急性加重风险的意义研究

Significance of YKL-40 Levels in Predicting the Risk of Acute Exacerbation in Chronic Obstructive Pulmonary Disease

目的:探讨甲壳质酶蛋白40(YKL-40)水平以及CXC趋化因子配体9(CXCL9)水平预测慢性阻塞性肺疾病(COPD)急性加重风险的意义。方法:2019年10月至2021年10月,选择本院呼吸与危重症医学科150例COPD患者(女性38例,男性112例)和150例正常人作为研究对象。ELISA法测定血清YKL-40、CXCL9水平,计算住院时间。本次住院治疗后1年内追踪COPD急性加重次数。结果:与对照组相比,在COPD病例中血清YKL-40水平显著升高(22.23±15.35ng/mL vs 63.96±13.66ng/mL,t=24.79,P<0.0001),而CXCL9水平无显著变化(17.92±9.01ng/mL vs 19.29±9.84ng/mL,t=1.26,P=0.210)。血清YKL-40随着COPD病例的GOLD分级升高而升高(1-2级:51.82±12.82ng/mL;3级:63.26±4.59ng/mL;4级:76.86±7.59ng/mL,F=96.92,P<0.0001)。与mMRC评分≤2的COPD患者相比,mMRC评分为2~3或≥3的COPD患者的血清YKL-40水平上调(58.35±15.37ng/mL vs 64.55±10.60ng/mL、68.79±12.66ng/mL,P<0.05)。在COPD患者中,血清YKL-40与FEV1(r=-0.668,P<0.001)和FEV1/FVC(r=-0.167,P=0.041)之间存在显著的负相关,以及血清YKL-40与IL-6(r=0.257,P=0.002)、TNF-α(r=0.522,P<0.001)和CRP(r=0.231,P=0.006)呈正相关。与住院时间≤8d的COPD患者相比,住院时间8~13d和≥13d的COPD患者血清YKL-40水平上调(57.31±15.82ng/mL vs 64.96±9.98ng/mL、69.79±11.58ng/mL,P<0.05)。急性加重次数≤2次患者入院时血清YKL-40水平显著低于急性加重次数>2次患者(58.77±15.66ng/mL vs 69.58±9.08ng/mL,t=5.17,P<0.001)。多元线性回归显示血清YKL-40与FEV1%呈负相关(OR=0.700,95%CI=-0.958,-0.272),和与住院时间≥13d呈正相关(OR=1.125,95%CI=1.007,1.472)。结论:入院时血清YKL-40水平与COPD患者的严重程度和不良预后呈正相关。

Objective:To explore the significance of chitin enzyme protein 40(YKL-40)and CXC chemokine ligand 9(CXCL9)in predicting the acute exacerbation risk of chronic obstructive pulmonary disease(COPD).Methods:From October 2019 to October 2021,150 COPD patients(38 females and 112 males)and 150 normal people were selected as the research objects.Serum YKL-40 and CXCL9 levels were measured by ELISA,and the hospitalization time was calculated.Follow up the number of acute exacerbations of COPD within one year after this hospitalization.Results:Compared with the control group,the serum YKL-40 level in COPD patients increased significantly(22.23±15.35 ng/ml vs 63.96±13.66 ng/ml,t=24.79,P<0.0001),while the level of CXCL9 did not change significantly(17.92±9.01 ng/ml vs 19.29±9.84 ng/mL,t=1.26,P=0.210).Serum YKL-40 increased with the increase of GOLD grade in COPD patients(grade 1-2:51.82±12.82 ng/ml;Grade 3:63.26±4.59 ng/ml;Grade 4:76.86±7.59 ng/mL,F=96.92,P<0.0001).Compared with COPD patients with mMRC score≤2,the serum YKL-40 level of COPD patients with mMRC score of 2~3 or≥3 was increased(58.35±15.37 ng/ml vs 64.55±10.60 ng/ml,68.79±12.66 ng/mL,P<0.05).In COPD patients,serum YKL-40 was negative correlated with FEV1(r=-0.668,P<0.001)and FEV1/FVC(r=-0.167,P=0.041),and serum YKL-40 was positively correlated with IL-6(r=0.257,P=0.002),TNF-α(r=0.522,P<0.001)and CRP(r=0.231,P=0.006).Compared with COPD patients whose hospitalization time was≤8 d,the serum YKL-40 level of COPD patients whose hospitalization time was 8~13 d and≥13 d was increased(57.31±15.82 ng/ml vs 64.96±9.98 ng/ml,69.79±11.58 ng/mL,P<0.05).The level of serum YKL-40 in patients with acute exacerbation≤2 times was significantly lower than that in patients with acute exacerbation>2 times(58.77±15.66 ng/ml vs 69.58±9.08 ng/ml,t=5.17,P<0.001).Multiple linear regression showed that serum YKL-40 was negatively correlated with FEV1%(OR=0.700,95%CI=-0.958,-0.272)and positively correlated with hospitalization time≥13 d(OR=1.125,95%CI=1.007,1.472).Conclusion:The level of serum YKL-40 at admission is positively correlated with the severity and poor prognosis of COPD patients.