作者：吉训恋，倪琼玮

单位：

570208 海南省海口市人民医院药学部；通信作者：倪琼玮，E-mail：nqwei79@hotmail.com

关键词：

慢性阻塞性肺疾病；肺部活化调节趋化因子；Clara 细胞蛋白 16；细胞间黏附分子 1；呼气冷凝液

Keywords：

Chronic obstructive pulmonary disease；Pulmonary activation regulated chemokine；Clara cell protein16；Intercellular adhesion molecule-1；Exhaled breath condensate

CLC：

R 563.9

DOI：

Funds：

海南省卫生计生行业科研项目（19A200163）

摘要：

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（PaCO 2 ）、动脉血氧分压（PaO 2 ）、第 1 秒用力呼气容积占预计值百分比（FEV 1 %）、第 1 秒用力呼气容积与用力肺活量比值（FEV 1 /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。

Abstract：

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 andICAM-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 EBCof patients with AECOPD. Methods　From June 2017 to June 2019，a total of 159 patients with COPD were selected from thePeople's Hospital of Haikou，including 99 cases with AECOPD（served as A group）and 60 cases with stable COPD（servedas 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 andC；clinical data was compared between good prognosis subgroup and poor prognosis subgroup，and influencing factors of short-term 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 ofpatients merged with 2 or more comorbidities，serum levels of CRP and PCT，CCL18，CC16 and ICAM-1 in EBC in poorprognosis subgroup were statistically significantly higher than those in good prognosis subgroup（P<0.05）；there was nostatistically significant difference in male ratio，age，course of disease，BMI，smoking rate，drinking rate，using time ofhormone，duration of mechanical ventilation，incidence of consciousness disorder，WBC，NLR，PaCO 2 ，PaO 2 ，FEV 1 %or FEV 1 /FVC between the two groups（P>0.05）.Multivariate Logistic regression analysis results showed that，merged with2 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 independentinfluencing 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% and63.64%，respectively. Conclusion　CCL18，CC16 and ICAM-1 in EBC significantly elevated in patients with COPD，and theabove three significantly increased in patients with AECOPD compared to those in patients with stable COPD；CCL18，CC16and ICAM-1 in EBC are independent influencing factors of short-term prognosis in patients with AECOPD，and the above threehave some predictive value on the short-term prognosis.

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