组织蛋白酶S与慢性阻塞性肺疾病肺功能及CT表型的关系

The association between Cathepsin S and pulmonary function and CT phenotypes in patients with chronic obstructive pulmonary disease

目的探讨慢性阻塞性肺疾病(慢阻肺)患者BALF中组织蛋白酶S在评估肺功能及CT表型中的价值。方法纳入2014年4月至2017年4月在上海市第六人民医院东院呼吸内科收治的慢阻肺稳定期患者46例,按GOLD分级分为Ⅰ级12例、Ⅱ级6例、Ⅲ级14例以及Ⅳ级14例。同期以胸痛伴慢性咳嗽或声音嘶哑为自觉症状在我院自愿进行纤维支气管镜及BALF检查,经各项检查证实为健康者29名,作为对照组。酶联免疫吸附测定法(ELISA)测定BALF中组织蛋白酶S和γ-干扰素的水平。高分辨率CT测量低衰减区域(LAA)占全肺体积的百分比(LAA%)、2倍气道壁厚度与气道直径比(2T/D)、管壁面积占总横截面积比(WA)。结果对照组、GOLD Ⅰ、Ⅱ、Ⅲ、Ⅳ级患者BALF中组织蛋白酶水平分别为(0.5±0.3)、(2.3±0.9)、(3.1±1.2)、(4.3±1.5)和(5.5±1.7)μg/L,各组间差异有统计学意义(F=6.639,P=0.000);各组组织蛋白酶S水平为GOLD Ⅳ组>GOLD Ⅲ组>GOLD Ⅱ组>GOLD Ⅰ组>健康对照组(均P<0.05);LAA 3级>LAA 2级>LAA 1级>LAA 0级(均P<0.01);组织蛋白酶S与FEV1/FVC、FEV1占预计值%、DLCO占预计值%呈显著负相关(均P<0.05),与RV/TLC%、LAA%、2T/D、WA和γ-干扰素呈显著正相关(均P<0.05)。结论组织蛋白酶S水平反映慢阻肺气流受限程度及肺气肿表型,并可能通过γ-干扰素参与到慢阻肺肺气肿和气流受限的发病机制中。

Objective To explore the value of cathepsin S in the bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD) in the evaluation of pulmonary function and CT phenotypes. Method From April 2014 to April 2017, 46 patients with stable COPD were enrolled, and 29 healthy volunteers served as the control group. The patients were divided into 4 subgroups: GOLD Ⅰ(n=12), GOLD Ⅱ(n=6), GOLD Ⅲ(n=14), GOLD Ⅳ(n=14). The levels of cathepsin S and IFN-γ in BALF were determined by enzyme-linked immunosorbent assay (ELISA). The percentage ratio of low attenuation area to total lung area (LAA%), two times the ratio of airway wall thickness to outer diameter(2T/D), and the ratio of wall area to total cross-sectional area (WA) were measured by HRCT. Results There were significant differences in the levels of cathepsin S in BALF between the groups (F=6.639, P=0.000). BALF cathepsin S levels were as follows: GOLD Ⅳ grou P>GOLD Ⅲ grou P>GOLD Ⅱ grou P>GOLD group Ⅰ>healthy control group (P value were all<0.05);LAA grade 3>LAA grade 2>LAA grade 1>LAA grade 0 (P value were all<0.05). Correlation analysis showed that BALF cathepsin S levels were correlated negatively with FEV1/FVC, FEV1% predicted, and DLCO%(r value was -0.065、-0.576、-0.392, respectively, P value were all<0.05), and but positively with RV/TLC%, LAA%, 2T/D, WA and IFN-γ(r value was 0.695, 0.497, 0.142, 0.309, 0.148, respectively, P value were all<0.05). Conclusion The levels of cathepsin S were associated with the degree of airflow limitation and emphysema phenotype in COPD.