淋巴细胞和Ⅲ型前胶原氨基端肽与肺气肿合并肺纤维化的关系

Correlation of lymphocytes and PⅢNP with the combined pulmonary fibrosis and emphysema

目的：观察肺气肿合并肺纤维化（CPFE）淋巴细胞亚型的分布和Ⅲ型前胶原氨基端肽（PⅢNP）水平及纤维化程度，探讨其炎症反应、免疫状态与肺纤维化（PF）的关系。方法：对2005—03／2007—03西安交通大学第一附属医院收治的21例CPFE、25例特发性肺纤维化（IPF）19例对照进行如下检测：光镜下观察肺活检标本的病理改变；对支气管肺泡灌洗液（BALF）进行炎细胞计数和分类；流式细胞术（FCM）检测BALF中T淋巴细胞亚型；放射免疫法检测BALF和血清PⅢNP水平。结果：活检病理结果发现，IPF组纤维化率高于CPFE组（P〈0．01），但两组纤维化率与是否吸烟均不相关（P〉0．05）；BALF炎细胞分类结果显示CPFE组细胞总数和淋巴细胞比例均高于IPF组和对照组（P〈0．05，P〈0．01）；FCM检测BALF发现CPFE组CD8＋T淋巴细胞百分比高于IPF组和对照组（P〈0．05）；CPFE组和IPF组CD4＋／CD8＋比值均明显低于对照组（P〈0．01）；三组之间CD4＋的百分率无统计学差异；CPFE组与IPF组血清PⅢNP检测值均高于对照组（P〈0．01），其中CPFE组血清PⅢNP检测值显著低于IPF组（P〈0．01）。BALF与血清PⅢNP水平呈正相关（γ=0．82）。结论：CPFE的PF病变具有自身特点和发展规律，香烟烟雾刺激可能并非其直接或主要致纤维化因素；CPFE肺组织局部具有较IPF和对照明显且以CD8＋T淋巴细胞增高为主的炎性反应，抗淋巴细胞炎症和免疫调节治疗可能有助于改善病情；血清PⅢNP可用作早期发现CPFE和监测PF治疗的指标。

AIM： To approach the relationships among inflammation, immune response, and fibrosis in combined pulmonary fibrosis and emphysema （CPFE） through the observation of distributions of lymphocyte subtypes, the variation of Pro-collagen III N-terminal peptide （PIIINP） expression and the severity of pulmonary fibrosis （PF） in CPFE. METHODS： From March 2005 to March 2007, 21 diagnosed cases of CPFE, 2.5 diagnosed cases of idiopathic pulmonary fibrosis （IPF） and 19 cases of controls were involved in the study from the First Affiliated Hospital of Xi＇an Jiaotong University. The patients were subjected to the following investigations including pathological changes in lung tissue biopsy specimens by light microscopy, counting and classification of inflammatory cells out of bronchoalveolar lavage fluids （BALF）, determination of Tlymphocyte subtypes by flow cytometry （FCM）, and detection of PIIINP level in BALF and blood serum by radioimmunoassay. RESULTS： The pathological data showed higher degree of fibrosis in IPF group than that in CPFE group （ P〈0.01）, but the level of fibrosis in the two Zgroups had nothing to do with smoking status （ P 〉 0.05）. The inflammatory cells and lymphocyte cells in BALF were more in CPFE group than those in IPF and control groups （ P 〈0. 05, P 〈 0. 01 respectively）. The FCM showed CPFE group had more CD8＋ T- lymphocytes than IPF and control groups （ P 〈 0. 05 ）, whereas CPFE and IPF groups showed significantly lower CD4 ＋/CD8 ＋ ratio than the control group （ P〈0.01 ）. There was no significantly statistical difference in the percentage of CD4 ~ T-lymphocytes among the three groups （P 〉 O. 05 ）. CPFE and IPF groups exhibited significantly higher level of blood PIIINP than the control group （P〈0.01）, while IPF group showed markedly higher level of blood PIIINP than CPFE group （ P 〈 0.01 ）. BALF and blood level of PIIINP were positively correlated （γ = 0.82）. CONCLUSION： The pulmonary fibrosis in CPFE shows intrinsic characteristics, with smoking not being the major or direct PF-driven factor. The CPFE group showed significant inflammation predomi- nated by T-lymphocytes, especially CD8 ＋ T-lymphocyte, as compared with the IPF and control groups, hence pointing to the fact that a novel anti-lymphocytes and immune regulation strategy may be useful for disease intervention. Blood serum PIIINP may be used as a marker for early detection of CPFE and also as a monitor for efficacy of treatments.