COPD频繁急性加重表型与炎性因子相关性研究

Correlation between frequent exacerbation phenotype of chronic obstructive pulmonary disease and inflammatory markers

目的研究COPD频繁急性加重表型的特点,寻找有效识别该表型的生物标志物,并可预测急性加重风险。方法此研究为一项前瞻性研究,纳入从2014年4月至2018年4月期间由北京大学首钢医院呼吸与危重症医学科收治的符合标准的COPD患者共190例,按照入选前一年的急性加重次数分为频繁急性加重组(98例)和非频繁急性加重组(92例),分别选取急性加重期(AE期)以及稳定期两个时期,记录基础CAT评分、血中降钙素原、C-反应蛋白在2组患者之间有无统计学差异;分别测定血中及呼出气冷凝液(EBC)中白介素-8(IL-8)、白三烯B4(LTB4)、8-异前列腺素(8-iso-PG)和血嗜酸性粒细胞(EOS),对比2组患者在不同时期各组数据有无统计学差异;将血EOS按不同计数方式(绝对值以及百分比)进行分组,分别对比上述各项数据,寻找有统计学意义的指标;随访两年,记录年急性加重频率。结果所有患者AE期血及EBC中的IL-8、LTB4、8-iso-PG和EOS中位数均高于稳定期,且有统计学意义(P<0.05);2组患者中AE期的IL-8(EBC)、稳定期的8-iso-PG(血)、随访两年的年急性加重次数分布差异均有统计学意义,AE期的IL-8(EBC)和随访期两年的年急性加重次数与不同加重次数分组呈正相关(P<0.05)。将患者按血EOS绝对值100个细胞/µL(0.1)、300个细胞/µL(0.3)为界值分组后,稳定期的8-iso-PG(EBC)、LTB4(血)与分组呈显著正相关(P<0.05)。将血EOS按百分比2%分组后,稳定期的LTB4(血)仍随血EOS百分比增高而增高,具有统计学意义(P<0.05),但未发现其与分组之间呈正相关。EOS不论以计数亦或百分比分组,与三年内的年急性加重频率之间均无相关性。结论COPD患者在急性加重期多项炎性指标均较其稳定期水平升高,其中急性加重期EBC中IL-8可能成为预测频繁急性加重表型的生物标志物。血嗜酸性粒细胞按不同分组方法得出结论有差异,稳定期EBC中的8-iso-PG、血中的LTB4可能与嗜酸性粒细胞增多表型相关。血嗜酸性粒细胞并不能良好的预测急性加重的风险。

ObjectiveTo characterize the phenotype of frequent acute exacerbations of chronic obstructive pulmonary disease (COPD), and to find biomarkers that can effectively identify this phenotype and predict the risk of acute exacerbations.MethodsThis was a prospective study that included 190 COPD patients admitted to the Department of Respiratory and Critical Care Medicine of Peking University Shougang Hospital. The patients were divided into a frequent exacerbation group (98 cases) and an infrequent exacerbation group (92 cases) according to the frequency of acute exacerbations in the year before enrollment. Then, the patients in the acute exacerbation period and stable period were monitored in each group. The levels of interleukin-8 (IL-8), leukotriene B4 (LTB4), 8-isoprostane (8-iso-PG), and eosinophils (EOS) in blood and exhaled breath condensate (EBC) were measured, and the data in different periods were analyzed between the two groups. Blood EOS were analyzed according to different counting methods (absolute value and proportion). Statistically significant indicators were identified. The frequency of acute exacerbations was recorded in a follow-up period of two years.ResultsThe median values of IL-8, LTB4, 8-iso-PG, and EOS in blood and EBC in patients who were in the acute exacerbation period were significantly higher than those in the stable stage (P<0.05). There were significant differences in the distribution of IL-8 in EBC during acute exacerbation, 8-iso-PG in blood during the stable period, and the frequency of acute exacerbations during the two-year follow-up period between the two groups. IL-8 in EBC during acute exacerbation and the annual frequency of acute exacerbations in the two years of follow-up were positively correlated with different groups (P<0.05). After grouping patients according to the absolute value of blood EOS of 100 cells/µL (0.1) and 300 cells/µL (0.3), the 8-iso-PG in EBC and LTB4 in blood during the stable stage were significant positively correlated with the different groups. After grouping blood EOS by a percentage of 2%, LTB4 in blood during the stable stage still increased significantly with the increase of blood EOS (P<0.05);however, no positive correlation was found between them. There was no correlation between EOS and the annual frequency of acute exacerbations within the three years, no matter grouped by count or percentage.ConclusionIn patients with COPD, multiple inflammatory indicators are higher in the acute exacerbation phase than in the stable phase. Among them, IL-8 in EBC during the acute exacerbation period may become a biomarker that predicts the frequent acute exacerbation phenotype. The significance of blood EOS is different according to grouping methods. The 8-iso-PG in EBC and LTB4 in blood during the stable phase may be associated with eosinophilia phenotype. Blood eosinophils are not a good predictor of the risk of an acute exacerbation.