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血清趋化因子白细胞介素8对慢性阻塞性肺疾病急性加重的预测价值
张景熙*,范韵鑫,白冲
0
(海军军医大学(第二军医大学) 长海医院呼吸与危重症医学科, 上海 200433
*通信作者)
摘要:
目的 探讨血清趋化因子白细胞介素(IL)-8对慢性阻塞性肺疾病(COPD)急性加重的预测价值。方法 纳入2015年9月至2016年5月在我院初诊或未进行规范化治疗的急性加重期COPD患者112例,根据血清IL-8水平将其分为高IL-8组(≥62 pg/mL)和低IL-8组(<62 pg/mL),比较两组患者的血常规检查指标,血清免疫球蛋白E(IgE)、IL-8、IL-6、肿瘤坏死因子α(TNF-α)、超氧化物歧化酶水平和呼出气一氧化氮以及肺功能检查指标。随访1年,记录患者自随访开始至第1次出现中重度急性加重的时间及随访期间急性加重次数。血清IL-8和各变量间的单因素分析采用Spearman相关分析,用Cox回归分析两组患者急性加重的相对危险度(RR),用Kaplan-Meier曲线分析随访12个月两组无急性加重患者所占比例的差异和风险比(HR)。结果 高、低IL-8组患者分别为47例和65例,IL-8水平[中位数(下四分位数,上四分位数)]分别为170.00(111.00,472.00)pg/mL和22.40(7.90,34.45)pg/mL。高IL-8组过敏性鼻炎患者比例高于低IL-8组[51.06%(24/47)vs 10.77%(7/65),P<0.01],COPD评估测试(CAT)评分高于低IL-8组(24.81±5.10 vs 19.38±4.27,P<0.01),既往急性加重次数多于低IL-8组[1.5(1.0,2.5)vs 1.0(0.0,1.5),P<0.01]。吸入支气管扩张剂前,高IL-8组用力呼气中期流速(FEF25%-75%)、FEF25%-75%占预计值的百分比、用力呼气75%用力肺活量流速(FEF75%)、FEF75%占预计值的百分比均低于低IL-8组[(0.73±0.55)L/min vs(1.26±1.15)L/min、(23.89±16.64)% vs(35.21±26.88)%、(0.32±0.19)L/min vs(0.57±0.53)L/min、(25.32±13.27)% vs(39.97±29.42)%,P均<0.05]。患者血清IL-8水平与一氧化碳弥散量占预计值的百分比(DLCO% Pred)呈负相关(r=-0.402 1,P=0.001 8),且高IL-8组DLCO% Pred低于低IL-8组[(51.52±26.41)% vs(72.98±18.70)%,P=0.029]。随时间累积高IL-8组急性加重的风险高于低IL-8组,RR为3.750(95% CI:1.200~11.716,P=0.029);高IL-8组距第1次发生急性加重的中位时间较低IL-8组短,HR为3.066(95% CI:1.053~8.927,P=0.039)。结论 血清IL-8水平增高对COPD急性加重具有一定预测价值,可能与COPD急性加重患者合并过敏体质和小气道功能、弥散功能受损加重有关。
关键词:  慢性阻塞性肺疾病  急性加重  趋化因子类  白细胞介素8
DOI:10.16781/j.0258-879x.2018.05.0480
投稿时间:2017-11-29修订日期:2018-03-06
基金项目:国家自然科学基金(81100017,81670016).
Predicting value of serum chemokine interleukin 8 for acute exacerbation of chronic obstructive pulmonary disease
ZHANG Jing-xi*,FAN Yun-xin,BAI Chong
(Department of Respiratory and Critical Care Medicine, Changhai Hospital, Navy Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To explore the predictive value of serum chemokine interleukin (IL)-8 for acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods A total of 112 COPD patients with acute exacerbation, who were initially diagnosed or did not receive standardized treatment in our hospital from Sep. 2015 to May 2016, were included in this study. According to serum level of IL-8, the patients were divided into high IL-8 group (≥ 62 pg/mL) and low IL-8 group (<62 pg/mL). The blood test results, serum levels of immunoglobulin E (IgE), IL-8, IL-6, tumor necrosis factor α (TNF-α), and superoxide dismutase (SOD), fractional exhaled nitric oxide (FeNO) and pulmonary function parameters were compared between the two groups. The interval time between beginning of follow-up and the first moderate to severe acute exacerbation and the times of acute exacerbation were recorded and compared between the two groups during one-year follow-up. Univariate analysis between serum IL-8 and variables was performed by Spearman correlation analysis. Cox regression was used to analyze the relative risk (RR) of acute exacerbation of the COPD patients in the two groups. Kaplan-Meier curve was used to analyze the proportion of the patients without acute exacerbation and hazard ratio (HR) during the follow-up in the two groups. Results The median levels of IL-8 were 170.00 (111.00, 472.00) pg/mL and 22.40 (7.90, 34.45) pg/mL in the high IL-8 group (n=47) and low IL-8 group (n=65), respectively. The proportion of allergic rhinitis cases and COPD assessment test (CAT) score were significantly higher in the high IL-8 group than those in the low IL-8 group (51.06%[24/47] vs 10.77%[7/65], P<0.01; 24.81±5.10 vs 19.38±4.27, P<0.01). The acute exacerbation times were significantly more in the high IL-8 group than those in the low IL-8 group (1.5[1.0, 2.5] vs 1.0[0.0, 1.5], P<0.01). Before inhaling bronchodilators, the high IL-8 group had significantly lower forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%), FEF25%-75% as percentage of predicted, forced expiratory flow at 75% of forced vital capacity (FEF75%) and FEF75% as percentage of predicted versus the low IL-8 group ([0.73±0.55] L/min vs[1.26±1.15] L/min,[23.89±16.64]% vs[35.21±26.88]%,[0.32±0.19] L/min vs[0.57±0.53] L/min, and[25.32±13.27]% vs[39.97±29.42]%, all P<0.05). The serum IL-8 level was significantly negatively correlated with diffusion capacity for carbon monoxide as percentage of predicted (DLCO%Pred; r=-0.402 1, P=0.001 8), and the DLCO%Pred was significantly lower in the high IL-8 group than that in the low IL-8 group ([51.52±26.41]% vs[72.98±18.70]%, P=0.029). The cumulative risk of acute exacerbation was significantly higher in high IL-8 group than that in the low IL-8 group, with RR being 3.75 (95% confidence interval[CI] 1.200-11.716, P=0.029). The median interval time to the first acute exacerbation was significantly shorter in the high IL-8 group than that in the low IL-8 group (HR=3.066, 95% CI 1.053-8.927, P=0.039). Conclusion Serum IL-8 can be used as a predictive biomarker for acute exacerbation of COPD patients, which may involve allergic constitution, small airway function deterioration, and decreased diffuse capacity among these patients.
Key words:  chronic obstructive pulmonary disease  acute exacerbation  chemokines  interleukin 8