慢性阻塞性肺疾病频繁急性发作的牙周及唾液指标筛查的研究

Screening of periodontal and salivary parameters in patients with frequent acute exacerbation of chronic obstructive pulmonary disease

目的筛选与慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)频繁急性发作风险相关的牙周指标及唾液炎症与细菌指标,为临床提供参考。方法收集2016年12月至2017年5月于首都医科大学附属北京朝阳医院呼吸科就诊的COPD稳定期患者38例[男性31例,女性7例,年龄(63.7±8.6)岁]检测患者的牙周指标并收集唾液。应用酶联免疫吸附测定法检测唾液样本中炎症因子水平,并应用基于16SrRNA基因的高通量测序方法检测样本中的细菌组成。随访所有患者12个月内COPD急性发作次数,并将患者分为频繁急性发作组(≥2次/年,10例)和非频繁急性发作组(<2次/年,28例)。结果单因素分析结果显示,频繁急性发作组年龄[(69.0±7.3)岁]显著高于非频繁急性发作组[(61.8±8.3)岁](P=0.02),余留牙数≤26颗的百分比[100%(10/10)]显著高于非频繁急性发作组[43%(12/28)](P=0.02),菌斑指数≤2.5的百分比(2/10)显著低于非频繁急性发作组[71%(21/28)](P=0.01);频繁急性发作组唾液炎症因子白细胞介素6(interleukin-6,IL-6)≤60 ng/L百分比、C反应蛋白(C-reactive protein,CRP)≤1 550μg/L百分比、基质金属蛋白酶8(matrix metalloproteinase-8,MMP-8)≤140μg/L百分比及纤维蛋白酶原(fibrinogen,Fib)≤90 mg/L百分比(分别为10%、30%、30%及30%)与非频繁急性发作组(上述指标分别为71%、71%、86%及71%)相比,差异均有统计学意义(P<0.05);频繁急性发作组与非频繁急性发作组相比,唾液中的绿弯菌门、厌氧绳菌刚、厌氧绳菌目、棒杆菌目、厌氧绳菌科、组织菌科、纤毛菌科、棒杆菌科、纤毛菌属、Moryella、Lachnoanaerobaculum及棒杆菌属的相对丰度差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,炎症因子IL-6>60 ng/L和细菌目水平棒杆菌目相对丰度>0.2在两组中差异均有统计学意义(P<0.05)。结论定期检测COPD患者唾液中炎症因子IL-6水平和唾液细菌棒杆菌目的相对丰度可以作为COPD频繁急性发作的相关指标。

Objective To screen the risk factors of patients with frequent acute exacerbation of chronic obstructive pulmonary disease(COPD)by detecting the clinical indicators of periodontitis and the level of bacterial and inflammatory markers in saliva.Methods Thirty-eight COPD patients in their stable period were recruited and detected from Beijing Chao-Yang Hospital,Capital Medical University during December 2016 to May 2017.The periodontal index were recorded.The levels of inflammatory factors in saliva samples were examined by using enzyme linked immunosorbent assay(ELISA).The bacteria composition in the saliva samples were identified by using 16SrRNA gene pyrosequencing.All patients were followed up and monitored for acute exacerbation of COPD for 12 months.The patients were divided into frequent acute exacerbation group(≥2 times/year,n=10)and non frequent acute exacerbation group(<2 times/year,n=28).Results In univariate analysis,the patients′average age of frequent acute exacerbation group(69.0±7.3)was significantly older than that of non-frequent acute exacerbation group(61.8±8.3)(P=0.02).The numbers of remaining teeth≤26[100%(10/10)]was significantly higher and plaque index≤2.5(2/10)in frequent acute exacerbation group was significantly lower compared with the remaining teeth≤26[43%(12/28)]and the plaque index≤2.5[71%(21/28)]in non-frequent acute exacerbation group(P=0.02,P=0.01).The proportions of salivary inflammatory factors interleukin-6(IL-6)level≤60 ng/L(10%),C-reactive protein(CRP)level≤1 550μg/L(30%),matrix metalloproteinase-8(MMP-8)level≤140μg/L(30%)and fibrinogen level≤90 mg/L(30%)in frequent acute exacerbation group were significantly lower compared with salivary inflammatory factors IL-6 level≤60 ng/L(71%),CRP level≤1 550μg/L(71%),MMP-8 level≤140μg/L(86%)and fibrinogen level≤90 mg/L(71%)in non-frequent acute exacerbation group(P<0.05).The differences of relative abundances of salivary bacteria,such as species of Chloroflexi,Anaerolineae,Anaeroales,Corynebacteriales,Anaerolineaceae,Tissierellaceae,Leptotrichiaceae,Corynebacteriaceae,Leptotrichia,Moryella,Lachnoanaerobaculum and Corynebacterium between frequent acute exacerbation group and non-frequent acute exacerbation group were significantly different(P<0.05).In multivariate logistics regression analysis,the level of IL-6>60 ng/L and the relative abundance of Corynebacteriales>0.2 had significant difference(P<0.05).Conclusions The level of IL-6 and the relative abundance of Corynebacteriales might be the markers of frequent acute exacerbation in COPD patients.