支气管肺泡灌洗液组织蛋白酶S与慢性阻塞性肺疾病严重程度的关系

Association between cathepsin S in bronchoalveolar lavage fluid and severity of chronic obstructive pulmonary disease

摘要:

目的 探讨慢性阻塞性肺疾病(COPD)患者支气管肺泡灌洗液(BALF)中组织蛋白酶S在综合评估分组中的价值。方法 入选2014年4月至2017年4月在上海市第六人民医院呼吸内科门诊随诊的COPD稳定期患者46例,根据COPD综合评估(CAT)结果分为4组:A组[CAT<10分、第1秒用力呼气容积(FEV1)占预计值百分比≥50％且近1年急性加重次数<2次]11例,B组(CAT≥10分、FEV1占预计值百分比≥50％且近1年急性加重次数<2次)7例,C组(CAT<10分、FEV1占预计值百分比<50％或近1年急性加重次数≥2次)13例,D组(CAT≥10分、FEV1占预计值百分比<50％或近1年急性加重次数≥2次)15例。同期纳入肺功能正常的健康自愿者29例作为对照组。酶联免疫吸附测定法(ELISA)测定BALF中组织蛋白酶S。高分辨率CT测量低衰减区域(LAA)占全肺体积的百分比(LAA％)。采用SPSS 16.0统计软件进行数据分析。结果 COPD组BALF中组织蛋白酶S水平显著高于对照组；组织蛋白酶S水平在不同病情严重程度中表现为:D组>C组>B组>A组(P<0.01)；在不同肺气肿程度中表现为:LAA 3级>LAA 2级>LAA 1级>LAA 0级(P<0.01)。单因素分析提示,LAA分级可显著影响组织蛋白酶S水平(F＝5.141,P<0.001)。相关分析结果提示,COPD患者BALF中蛋白酶S水平与前1年急性加重频率(r=0.142,P=0.003)、CAT评分(r=0.309,P=0.017)、LAA％(r=0.497,P<0.001)呈显著正相关。结论 组织蛋白酶S水平能够反映COPD严重程度,可作为判断COPD病情严重度的标志物,具有一定的治疗指导作用。

Abstract:

Objective To investigate the value of cathepsin S in bronchoalveolar lavage fluid (BALF) in comprehensive assessment of the patients with chronic obstructive pulmonary disease (COPD). Methods A total of 46 patients with stable COPD were included as the study (COPD) group, who paid follow-up visits at the Department of Respiratory Medicine of our Hospital from April 2014 to April 2017. They were divided, based on COPD assessment test (CAT) results, into group A(n=11), B(n=7), C(n=13), and D(n=15). Group A was assigned as CAT scored <10, the ratio of forced expiratory volume in the first second (FEV1) to the expected value ≥50%, and the frequency of acute exacerbations during last year less than twice. Group B as CAT scored ≥10, the ratio ≥50%, and the frequency less than twice. Group C as CAT scored <10, the ratio <50%, or the frequency more than twice. Group D as CAT scored ≥10, the ratio < 50%, or the frequency more than twice. As the control group, 29 healthy volunteers were taken from the same frame with normal lung function. The levels of cathepsin S in BALF were determined with enzyme-linked immunosorbent assay (ELISA). High-resolution CT (HRCT) was used to measure the percentage ratio of low-attenuation area (LAA) to total lung area (LAA%). Results BALF cathepsin S levels in the COPD group were significantly higher than that of the control group. BALF cathepsin S levels related to the severity of the disease as group D > group C > group B > group A (P<0.01) and to the degree of emphysema as LAA grade 3 > LAA grade 2 > LAA grade 1 > LAA grade 0 (P<0.01). The results of univariate analysis showed that LAA classification significantly affected the level of cathepsin S (F＝5.141,P<0.001). Correlation analysis indicated that BALF cathepsin S level in COPD patients correlated positively to the frequency of acute exacerbation in the previous year (r=0.142, P=0.003), CAT score (r=0.309, P=0.017) and LAA% (r=0.497, P<0.001). Conclusion The BALF cathepsin S level reflects the severity of COPD and can be used as a biomarker in the assessment and treatment of COPD.