特发性肺纤维化患者肺泡灌洗液和血清中Napsin A、KL-6、SP-A、SP-D表达的意义及与肺功能相关性

目的特发性肺纤维化(IPF)是一种不明原因的慢性进行性间质性肺疾病。其发病率、死亡率均较高。但IPF的发病机制至今尚未完全清楚,临床上对此病发生发展的掌握不够,检验指标的敏感性及特异性不高,从而影响诊断及临床判断的准确性。因此寻找IPF发生发展的生物标记物成为近年来较为热门的研究方向。方法挑选2017年3月-2019年3月间在我院就诊并诊断明确的30例IPF患者入组IPF观察组,20例临床症状类似的I期肺结节病患者作为阴性对照组。采用双抗体夹心酶联免疫吸附(ELISA)法检测IPF和I期肺结节病对照组BALF和血清中Napsin A/KL-6/SP-A/SP-D水平,并对患者的肺功能进行检测,评估上述生物标记物与肺纤维化病程进展的相关性。结果IPF组患者的血清/肺泡灌洗液中Napsin A/KL-6/SP-A/SP-D水平均明显高于由I期肺结节病阴性对照组(P<0.05)。灌洗液中Napsin A/KL-6/SP-D含量与肺通气功能呈负相关(P<0.05),而Napsin A/KL-6含量与弥散功能呈现负相关(P<0.05)。血清中Napsin A/KL-6/SP-A/SP-D水平均与肺通气功能呈负相关(P<0.05),Napsin A/KL-6血清含量与肺弥散功能呈明显负相关(P<0.05),与肺泡灌洗液检测结果一致。结论Napsin A/KL-6/SP-A/SP-D在IPF患者灌洗液中的含量亦显著升高。其中血清Napsin A/KL-6水平相关度最高,高水平的血清及灌洗液中Napsin A/KL-6浓度提示IPF病灶进展,且与肺通气功能及弥散指标呈负相关,可作为诊断IPF严重程度判断的指标之一。而SP-A、SP-D也可以作为IPF早期的一种早期预测指标,敏感性特异性差于Napsin A/KL-6,但SP-D对于肺功能下降、肺纤维化早期炎症反应,优于SP-A。

Significance of expression of Napsin A,KL 6,SP-A and SP-D in alveolar lavage fluid and serum of patients with idiopathic pulmonary fibrosis and its correlation with pulmonary function

Objective Idiopathic pulmonary fibrosis is an interstitial pulmonary disease with unknown cause,chronic and progressive fibrosis,and its incidence and mortality are high.However,the pathogenesis of IPF is not completely clear,the clinical grasp of the development of the disease is not enough,and the sensitivity and specificity of the test indexes are not high,thus affecting the accuracy of diagnosis.Finding biomarkers for the occurrence and development of IPF has become a hot research direction in recent years.Methods 30 patients with IPF diagnosed and treated were selected as the IPF group and 20 patients with stage I pulmonary sarcoidosis with similar clinical symptoms as the control group.The levels of Napsin A/KL-6/SP-A/SP-D in IPF and stage I pulmonary sarcoidosis were detected by double antibody sandwich enzyme-linked immunosorbent assay(ELISA)in BALF and serum,and the pulmonary function of the patients was detected to evaluate the correlation with the above indexes.Results The results showed that the levels of Napsin A/KL-6/SP-A/SP-D in serum and lavage fluid of patients in the IPF group were significantly higher than those in the control group.The level of Napsin A/KL-6/SP-D in lavage fluid was negatively correlated with pulmonary ventilation function(P<0.05),and the level of Napsin A/KL-6 was negatively correlated with diffusion function(P<0.05).The level of serum Napsin A/KL-6/SP-A/SP-D was negatively correlated with pulmonary ventilation function(P<0.05).Conclusion The levels of Napsin A/KL-6/SP-A/SP-D increase significantly in alveolar lavage fluid of IPF patients.The high level of Napsin A/KL-6 in serum and lavage fluid indicates the progress of IPF,which can be used as one of the indexes to judge the severity of IPF.The high level of Napsin A/KL-6 concentration in serum and lavage fluid indicates the progress of IPF focus,and is negatively correlated with pulmonary ventilation function and diffusion index,which can be used as one of the indexes to judge the severity of IPF.SP-A and SP-D can also be used as an early predictive index of IPF,but the sensitivity and specificity of them are lower than that of Napsin A and KL-6.