慢性阻塞性肺疾病急性加重期患者呼气冷凝液中肺部活化调节趋化因子、Clara细胞蛋白16、细胞间黏附分子1水平变化及其与患者短期预后的关系研究

Changes and Relations to Short-term Prognosis of CCL18,CC16 and ICAM-1 in Exhaled Breath Condensate of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

背景目前,关于血清肺部活化调节趋化因子(CCL18)、Clara细胞蛋白16(CC16)、细胞间黏附分子1(ICAM-1)与慢性阻塞性肺疾病(COPD)关系的研究较多,但关于其在慢性阻塞性肺疾病急性加重期(AECOPD)患者呼气冷凝液(EBC)中的变化研究报道较少。目的分析AECOPD患者EBC中CCL18、CC16、ICAM-1水平变化及其与患者短期预后的关系。方法选取2017年6月-2019年6月海口市人民医院收治的COPD患者159例,其中急性加重期99例(A组),缓解期60例(B组);另选取本院同期体检健康者60例作为C组。根据短期预后将99例AECOPD患者分为预后良好亚组24例和预后不良亚组75例。比较A、B、C组受试者EBC中CCL18、CC16、ICAM-1水平;比较预后良好亚组、预后不良亚组患者临床资料,AECOPD患者短期预后的影响因素分析采用多因素Logistics回归分析;绘制受试者工作特征曲线(ROC)以评价EBC中CCL18、CC16、ICAM-1水平对AEPOCD患者短期预后的预测价值。结果A组受试者EBC中CCL18、CC16、ICAM-1水平高于B、C组,B组受试者EBC中CCL18、CC16、ICAM-1水平高于C组(P<0.05)。预后不良亚组患者合并症数量≥2个者所占比例,血清C反应蛋白(CRP)、降钙素原(PCT)水平及EBC中CCL18、CC16、ICAM-1水平高于预后良好亚组(P<0.05);两组患者男性比例、年龄、病程、体质指数(BMI)、吸烟率、饮酒率、激素使用时间、机械通气时间、意识障碍发生率、白细胞计数(WBC)、中性粒细胞与淋巴细胞比值(NLR)、动脉血二氧化碳分压(PaCO2)、动脉血氧分压(PaO2)、第1秒用力呼气容积占预计值百分比(FEV1%)、第1秒用力呼气容积与用力肺活量比值(FEV1/FVC)比较,差异无统计学意义(P>0.05)。多因素Logistic回归分析结果显示,合并症数量≥2个〔OR=2.252,95%CI(1.744,3.760)〕,血清CRP〔OR=2.210,95%CI(1.737,3.580)〕、PCT〔OR=2.049,95%CI(1.687,3.325)〕水平及EBC中CCL18〔OR=2.773,95%CI(1.857,4.336)〕、CC16〔OR=2.678,95%CI(1.801,3.985)〕、ICAM-1〔OR=1.923,95%CI(1.589,3.012)〕水平是AECOPD患者短期预后的独立影响因素(P<0.05)。ROC曲线分析显示,EBC中CCL18、CC16、ICAM-1水平预测AECOPD患者短期预后的曲线下面积(AUC)分别为0.856〔95%CI(0.435,0.902)〕、0.820〔95%CI(0.401,0.842)〕、0.705〔95%CI(0.380,0.758)〕,灵敏度分别为89.90%、82.83%、76.77%,特异度分别为78.79%、70.71%、63.64%。结论COPD患者EBC中CCL18、CC16、ICAM-1水平明显升高,且急性加重期患者高于稳定期患者;EBC中CCL18、CC16、ICAM-1水平是AECOPD患者短期预后的独立影响因素,对AECOPD短期预后具有一定预测价值。

Background There are many reports about relations of serum levels of CCL18,CC16 and ICAM-1 with chronic obstructive pulmonary disease(COPD),however there are few reports about changes of CCL18,CC16 and ICAM-1 in exhaled breath condensate(EBC)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Objective To analyze the changes and relations to short-term prognosis of CCL18,CC16 and ICAM-1 in EBC of patients with AECOPD.Methods From June 2017 to June 2019,a total of 159 patients with COPD were selected from the People’s Hospital of Haikou,including 99 cases with AECOPD(served as A group)and 60 cases with stable COPD(served as B group),meanwhile a total of 60 healthy people admitted to this hospital for physical examination were selected as C group.All of the 99 patients with AECOPD were divided into good prognosis subgroup(n=24)and poor prognosis subgroup(n=75)according to short-term prognosis.Comparison of CCL18,CC16 and ICAM-1 in EBC was conducted among groups A,B and C;clinical data was compared between good prognosis subgroup and poor prognosis subgroup,and influencing factors of shortterm prognosis in patients with AECOPD were analyzed by multivariate Logistic regression analysis;predictive value of CCL18,CC16 and ICAM-1 in EBC in short-term prognosis of patients with AECOPD was evaluated by ROC curve.Results CCL18,CC16 and ICAM-1 in EBC in A group were statistically significantly higher than those in groups B and C,meanwhile CCL18,CC16 and ICAM-1 in EBC in B group were statistically significantly higher than those in C group(P<0.05).Proportion of patients merged with 2 or more comorbidities,serum levels of CRP and PCT,CCL18,CC16 and ICAM-1 in EBC in poor prognosis subgroup were statistically significantly higher than those in good prognosis subgroup(P<0.05);there was no statistically significant difference in male ratio,age,course of disease,BMI,smoking rate,drinking rate,using time of hormone,duration of mechanical ventilation,incidence of consciousness disorder,WBC,NLR,PaCO2,PaO2,FEV1%or FEV1/FVC between the two groups(P>0.05).Multivariate Logistic regression analysis results showed that,merged with 2 or more comorbidities〔OR=2.252,95%CI(1.744,3.760)〕,serum levels of CRP〔OR=2.210,95%CI(1.737,3.580)〕and PCT〔OR=2.049,95%CI(1.687,3.325)〕,CCL18〔OR=2.773,95%CI(1.857,4.336)〕,CC16〔OR=2.678,95%CI(1.801,3.985)〕and ICAM-1〔OR=1.923,95%CI(1.589,3.012)〕in EBC were independent influencing factors of short-term prognosis in patients with AECOPD(P<0.05).ROC curve analysis showed that,AUC,sensibility and specificity of CCL18 in EBC in predicting short-term prognosis in patients with AECOPD was 0.856〔95%CI(0.435,0.902)〕,89.90%and 78.79%,respectively,those of CC16 in EBC were 0.820〔95%CI(0.401,0.842)〕,82.83%and 70.71%,respectively,those of ICAM-1 in EBC were 0.705〔95%CI(0.380,0.758)〕,76.77%and 63.64%,respectively.Conclusion CCL18,CC16 and ICAM-1 in EBC significantly elevated in patients with COPD,and the above three significantly increased in patients with AECOPD compared to those in patients with stable COPD;CCL18,CC16 and ICAM-1 in EBC are independent influencing factors of short-term prognosis in patients with AECOPD,and the above three have some predictive value on the short-term prognosis.