慢性阻塞性肺疾病频繁发作患者常见表型临床特征及痰炎性因子分析

Analysis of clinical features and inflammatory factors in induced sputum in common phenotypes of COPD with frequent exacerbations

目的分析频繁发作和非频繁发作的慢性支气管炎（chronic bronchitis，CB）、肺气肿、哮喘-慢性阻塞性肺疾病重叠综合征（asthma-chronic obstructive pulmonary disease overlap syndrome，ACOS）患者临床特征及诱导痰炎性细胞、递质的异质性。方法将我院2016年11月至2017年9月收治的91例慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）急性加重期患者分为CB、肺气肿或ACOS表型，其中频繁发作者44例，非频繁发作者47例。分析其临床资料、诱导痰炎性细胞、γ干扰素、肿瘤坏死因子α、白细胞介素4、白细胞介素13的差异。结果频繁发作患者第1秒用力呼气容积占预计值百分比（forced expiratory volume in the first second as percentage of predicted value，FEV1%）为（47.0±13.1）%，明显低于非频繁发作患者的（56.2±10.2）%，两者比较差异有统计学意义（P=0.000）。频繁发作患者第1秒用力呼气量占用力肺活量的百分比（forced expiratory volume for the first second percentage of FVC，FEV1/FVC%）为（54.3±9.3）%，明显低于非频繁发作患者的（60.1±7.3）%，两者比较差异有统计学意义（P=0.001）。频繁发作患者中GOLDⅢ、Ⅳ级的患者比例、诱导痰中中性粒细胞百分比、肿瘤坏死因子α、γ干扰素水平明显高于非频繁发作患者（P均〈0.05）。其中FEV1/FVC%、肿瘤坏死因子α是COPD患者频繁发作的独立危险因子（P值分别为0.032、0.021）。CB表型频繁发作患者FEV1%[（47.9±14.9）%]比非频繁发作患者[（57.2±10.9）%]显著降低（P=0.049）；CB表型频繁发作患者FEV1/FVC%为（53.4±9.5）%，明显低于非频繁发作患者的（60.3±6.9）%，两者比较差异有统计学意义（P=0.022）。CB表型频繁发作患者诱导痰中中性粒细胞百分比、肿瘤坏死因子α水平较非频繁发作患者明显增高（P均〈0.01）。肺气肿表型频繁发作患者与非频繁发作患者相比病程更长（P〈0.05）、FEV1%和FEV1/FVC%更低（P均〈0.05）、GOLDⅢ级患者比例及诱导痰TNF-α更高，但痰炎症细胞数量、比例及γ干扰素、白细胞介素4、白细胞介素13水平比较差异均无统计学意义（P均〉0.05）。ACOS表型频繁发作患者GOLDⅢ级比例、诱导痰IL-13水平明显高于非频繁发作患者（P均〈0.05）。结论肺功能、疾病严重程度、病程以及痰中性粒细胞百分比、肿瘤坏死因子α或白细胞介素13有助于判断频繁发作高风险的患者。

Objective To compare the clinical characteristics of chronic bronchitis （CB）, emphysema （EM）, asthma - chronic obstructive pulmonary disease overlapping syndrome （ACOS） with frequent exacerbations （FE） or infrequent exacerbations （iFE）and induced sputum inflammatory cells and the heterogeneity of the transmitter.MethodsNinety-one cases of chronic obstructive pulmonary disease（COPD）with acute exacerbation were divided into CB, EM or ACOS phenotype, among which 44 were frequent, and 47 were non frequent.The clinical data, induced sputum inflammatory cells, interferon-γ（IFN-γ）, tumor necrosis factor-α（TNF-α）, interleukin（IL）-4, IL-13 were analyzed. ResultsThe FEV1% was （47±13.1）%, significantly lower than that of non frequent episodes （（56.2±10.2）%）, and the difference was statistically significant（P=0.049）. The FEV1/FVC% was （54.3±9.3）%, significantly lower than that of non frequent episodes （60.1±7.3）%, and there was a significant difference between them （P=0.001）. The proportion of patients with GOLD III and IV, the percentage of neutrophils in induced sputum, tumor necrosis factor -α（TNF-α） and interferon -γin the patients with frequent episodes were significantly higher than those with non frequent episodes （P〈0.05）. Among them, FEV1/FVC% and TNF-αwere independent risk factors for COPD patients （P=0.032, 0.021）. The FEV1% of patients with CB phenotypic frequent episodes were （47.9±14.9）%, significantly lower than that of non frequent episodes （（57.2±10.9）% ）（P=0.000）, and FEV1/FVC% was （53.4±9.5）% in patients with CB frequent episodes, significantly lower than that of non frequent episodes （（60.3±6.9）%）, and the difference was statistically significant （P=0.022）, while the level of N%, TNF-α in induced sputum were significantly higher in CB phenotype subjects with FE than those in subjects with iFE（P〈0.01）. Patients with frequent episodes of emphysema had longer duration of disease （P〈0.05）, lower FEV1% and FEV1/FVC%（P〈0.05）, the proportion of GOLD III patients and the induced sputum TNF-αwere higher, but there was no significant difference in the number and proportion of phlegm inflammatory cells, interferon -γ, interleukin 4 and interleukin 3.The level of GOLD III and the IL-13 level of induced sputum in patients with frequent ACOS phenotype were significantly higher than those in patients with non frequent episodes （P〈0.05）.ConclusionThe lung function, the severity of the disease, the course of the disease, and the percentage of sputum neutrophils, tumor necrosis factor -α, or interleukin 13 are helpful in diagnosing patients with high risk of frequent episodes.