Department of respiratory and critical care medicine,Gulou clinical medical college,Nanjing University of traditional Chinese Medicine,Nanjing
目的：探究在真实世界中支气管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中趋化因子CCL2(Chemokine (C-C motif) ligand 2)和GAP评分对IPF预后的判断价值以及两者之间的相关性。方法：回顾性分析了2017年1月至2019年12月在南京大学医学院附属鼓楼医院住院确诊为IPF的患者35例,同期收集了因慢性咳嗽(Chronic cough,CC)就诊、但无其他肺部疾病或其他器官疾病的门诊患者10例。比较两组患者的性别、年龄、用力肺活量(Forced vital capacity, FVC)、一氧化碳弥散量(Diffusing capacity for carbon monoxide,DLCO)(CC组除外)、血气分析等指标的差异,同时检测血清中CCL2以及BALF中CCL2的浓度,分析不同GAP组别间CCL2的差异、患者生存时间的差别以及在CCL2与GAP评分之间的相关性。结果：与对照组相比,IPF组氧合指数、FVC%均降低(p<0.05),血清和BALF中CCL2均升高(p<0.05)。与对照组相比,IPF组BALF中淋巴细胞降低、中性粒细胞增加、巨噬细胞无差异。在相关性方面,BALF中CCL2与FVC%(r=-0.488,p<0.01)、DLCO%( r=-0.581,p<0.01)均呈负相关,然而血清中CCL2与FVC%(r=-0.088,p=0.617)、DLCO%(r=-0.178,p=0.320)相关性不强。并且受试者操作特征曲线分析(Receiver operating characteristic curve, ROC)曲线显示,BALF中CCL2水平大于等于363.74pg/ml时,患者死亡率增加。随后依据GAP评分对IPF患者分期,结果显示血清中CCL2水平在IPF组(I、II、III期)中无差异,但在BALF中,除了I期与对照组之间CCL2水平差异不明显外,IPF组II期与对照组、III期与对照组、IPF组(I、II、III期)之间CCL2水平均有明显不同(p<0.05)。在肺功能中,II期和III期较I期FVC%、DLCO%均显著下降(p<0.05),II期和III期之间FVC%、DLCO%差异不大。进一步生存分析显示,II期和III期患者生存期显著低于I期患者(p<0.05),但II期和III期之间生存期无明显差别。探讨BALF中CCL2与GAP评分相关性发现两者存在强烈正相关(r=0.847,P<0.01)。结论：本研究结果不仅验证了BALF中CCL2和GAP评分对预测IPF预后的价值,同时首次揭示了不同GAP分期中BALF中CCL2水平具有差异性、且BALF中CCL2与GAP评分具有强相关性。
Objective: To explore the prognostic value of chemokine CCL2 (C-C motif) and gap score in bronchoalveolar lavage fluid (BALF) in the real world.Methods: 35 patients with IPF hospitalized in Gulou Hospital Affiliated to Medical College of Nanjing University from January 2017 to December 2019 were analyzed retrospectively. At the same time, 10 outpatients with chronic cough (CC) but no other lung diseases or other organ diseases were collected. The differences of gender, age, forced vital capacity (FVC), diffusion capacity for carbon monoxide (DLCO) (except CC group) and blood gas analysis between the two groups were compared. At the same time, the concentrations of CCL2 in serum and BALF were detected, and the differences of CCL2 between different gap groups were analyzed The difference of survival time and the correlation between CCL2 and gap score. Results: compared with the control group, the oxygenation index and FVC% in IPF group decreased (P < 0.05), and CCL2 in serum and BALF increased (P < 0.05). Compared with the control group, there was no difference in lymphocytes, neutrophils and macrophages in BALF in IPF group. In terms of correlation, CCL2 was negatively correlated with FVC% (r = -0.488, P < 0.01) and DLCO% (r = -0.581, P < 0.01) in BALF, but there was no strong correlation between CCL2 and FVC% (r = -0.088, P = 0.617) and DLCO% (r = -0.178, P = 0.320) in serum, and receiver operating characteristic curve (ROC) The curve shows that when the level of CCL2 in BALF is greater than or equal to 363.74pg/ml, the mortality of patients increases. Then, according to the gap score for the staging of IPF patients, the results show that the level of CCL2 in serum has no difference in IPF group (phase I, II and III), but in BALF, except that there is no significant difference in CCL2 level between phase I and control group, phase III and control group, IPF group (phase I, II and III) The levels of CCL2 were significantly different between the two groups (P < 0.05). In pulmonary function, FVC% and DLCO% in stage II and III were significantly lower than those in stage I (P < 0.05), and there was little difference in FVC% and DLCO% between stage II and III. further survival analysis showed that the survival time of stage II and III patients was significantly lower than that of stage I patients (P < 0.05) , but there was no significant difference in survival between stage II and stage III. it was found that there was a strong positive correlation between CCL2 and gap score in BALF (r = 0.847, P < 0.01).Conclusion: This study further verified that CCL2 and gap scores in BALF can predict the prognosis of IPF. At the same time, it was the first time to explore the difference of CCL2 level in BALF in different gap stages, and there is a strong correlation between CCL2 and gap scores in BALF.