特发性肺纤维化急性加重期证候与血清生物标志物的相关性研究

Study on Correlation Between Syndromes of Acute Exacerbation of Idiopathic Pulmonary Fibrosis and Serum Biomarkers

目的通过分析特发性肺纤维化急性加重期(AE-IPF)患者证候与血清生物标志物的关系,为中医辨证治疗提供参考。方法采用观察性研究设计,收集2019年3月至2019年11月三个中心的AE-IPF患者76例,其中痰热壅肺证26例、痰浊阻肺证50例,并纳入健康志愿者10例作为对照。采用ELISA测定患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平,分析与中医证候的相关性。结果AE-IPF患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平均显著高于健康对照组。血清CCL18、HMGB1、KL-6、MMP-7和SP-D水平在痰热壅肺证和痰浊阻肺证患者间无显著性差异(P>0.05),而血清SP-A水平存在显著性差异(P<0.05)。结论血清SP-A与AE-IPF证候存在一定的相关性,血清SP-A的浓度升高,与痰热壅肺证关系越密切,反之,血清SP-A浓度降低,则与痰浊阻肺证关系越密切。AE-IPF痰热壅肺证患者的预后可能较痰浊阻肺证患者更差。

Objective To analyze the correlation between Traditional Chinese Medicine(TCM) syndromes of acute exacerbation of idiopathic pulmonary fibrosis(AE-IPF) and serum bio-markers to provide references for the TCM syndromes differentiation.Methods An observational study was adopted. From March 2019 to November 2019, 76 AEIPF patients from three centers were included, which included 26 cases with phlegm-heat syndrome and 50 cases with phlegm-turbid lung syndrome. Ten healthy volunteers were also been enrolled as control at the same time. Serum biomarkers, including CCL18, HMGB1, KL-6, MMP-7, SP-A, SP-D were tested in both IPF patients and healthy volunteers by ELISA. Results The levels of serum CCL18, HMGB1, KL-6, MMP-7, SP-A and SP-D in AE-IPF patients were significantly higher than that in healthy volunteers. There were significant differences in serum SP-A level between phlegm-heat syndrome and phlegm obstruction syndrome with no statistical difference in serum CCL18,HMGB1, KL-6, MMP-7, SP-D.Conclusion A higher level in serum SP-A may suggest differentiation of phlegm-heat syndrome with a lower level indicating phlegm-turbidity syndrome. AE-IPF patients with phlegm-heat syndrome may have a worse condition and prognosis.