阿奇霉素对有无幽门螺杆菌感染慢性阻塞性肺疾病急性加重预防作用的临床研究

目的：探讨阿奇霉素（AZ）对有无幽门螺杆菌（HP）感染慢性阻塞性肺疾病（COPD）急性加重的预防作用。方法：前瞻性选择2015年1月~2015年12月来我院接受治疗的COPD稳定期患者138例为研究对象。根据患者有无HP感染分为HP阳性组（HP+，n=32）和HP阴性组（HP-，n=106）。根据AZ及安慰剂（PL）使用情况又分为：HP+/AZ组、HP+/PL组、HP-/AZ组、HP-/PL组，各18例、14例、56例和50例。应用C-13呼气试验检测系统进行HP检测，判断HP阳性或阴性。所有患者入组时应用肺功能仪进行肺功能检测，主要指标有FEV1、FEV1占预计值百分比、FVC、FVC占预计值百分比、FEV1/FVC。按照GOLD分级将COPD患者分为I期、II期、III期、IV期。CRP水平，sTNFR75水平，3个月、6个月后CRP水平及sTNFR75水平测定应用ELISA试剂盒采用酶联免疫吸附法测定。以无COPD急性加重人数/分组总人数作为无COPD急性加重患者比例，并记录1~12月份各组无COPD急性加重患者比例。采用Kaplan-Meier法绘制无COPD急性加重患者比例曲线、Log-rank法进行无COPD急性加重患者比例曲线比较。结果：COPD患者HP阳性组（HP+/AZ、HP+/PL）与HP阴性组（HP-/AZ、HP-/PL）在性别、年龄、有吸烟史例数、有嗜酒史例数、过去1年住院史、FEV1、FEV1占预计值比例、FVC、FEV1/FVC、GOLD等级、基础CRP水平、基础sTNFR75水平方面差异无统计学意义（P＞0.05），研究对象具有可比性。HP+/AZ组首次出现急性加重时间为（10.24±4.65）个月，HP+/PL组首次出现急性加重时间为（7.52±3.38）个月，HP-/AZ组首次出现急性加重时间为（8.05±4.68）个月，HP-/PL组首次出现急性加重时间为（5.52±5.18）个月。Log-rank显示，HP+/AZ组与HP+/PL组、HP-/AZ组、HP-/PL组之间差异有统计学意义（P＜0.05），其余组间差异无统计学意义（P＞0.05）。HP+/AZ组、HP+/PL组、HP-/AZ组、HP-/PL组COPD患者，3个月、6个月CRP水平与基础水平相比差异有统计学意义（P＜0.05）； HP+/AZ组COPD患者3个月、6个月sTNFR75水平与基础水平相比差异有统计学意义（P＜0.05）。HP+/PL组、HP-/AZ组、HP-/PL组COPD患者，3个月、6个月CRP及sTNFR75水平与HP+/AZ组相比差异有统计学意义（P＜0.05）。结论：AZ对HP感染的COPD急性加重患者具有预防作用，这或许与肿瘤坏死因子通路有关。

Clinical Study of Azithromycin on the Prevention of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with or without Helicobacter Pylori infection

Objective: To investigate the preventive effect of azithromycin (AZ) on acute exacerbation of chronic obstructive pulmonary disease (COPD) with or without Helicobacter pylori (HP). Methods: 138 patients with stable?COPD in our hospital from Jan 2015 to Dec 2015 were selected as study subjects. The patients were divided into HP positive group (HP+, n=32) and HP negative group (HP-, n=106) according to whether or not the patients had HP infection. According to the use of AZ and placebo (PL), they were divided into group HP+/AZ, group HP+/PL, group HP-/AZ and group HP-/PL, each with 18 cases, 14 cases, 56 cases and 50 cases. The C-13 breath test system was used for HP test to determine whether HP was positive or negative. All patients into the group, the use of lung function instrument for pulmonary function test, the main indicators were FEV1, FEV1, accounting for the expected percentage, FVC, FVC, accounting for the expected value of percentage, FEV1/FVC. According to the GOLD classification, COPD patients were divided into I, II, III and IV phases. CRP levels, sTNFR75 levels, levels of CRP and sTNFR75 after 3 and 6 months were measured by enzyme-linked immunosorbent assay using the ELISA kit. The proportion of patients without acute exacerbation of COPD / group as the proportion of patients without COPD exacerbation was recorded, and the proportion of patients without acute exacerbation of COPD in 1~12 months was recorded. The proportion curve of acute exacerbation of no COPD was drawn by Kaplan-Meier, and the proportion curve of acute exacerbation of non COPD patients was compared by Log-rank method. Results: HP patients with COPD positive group (HP+/AZ, HP+/PL) and HP negative group (HP-/AZ, HP-/PL) in gender, age, smoking history, drinking history of the number of cases, the number of cases over the past 1 years in history, FEV1, FEV1%, FVC, FEV1/FVC, GOLD, CRP, the level of basic level the basal sTNFR75 level, the difference was not statistically significant (P>0.05), and comparability study. The HP+/AZ group appeared for the first time for the time of acute exacerbation (10.24±4.65) months, HP+/PL group appeared for the first time for the time of acute exacerbation (7.52±3.38) months, HP-/AZ group appeared for the first time for the time of acute exacerbation (8.05±4.68) months, HP-/PL group appeared for the first time for the time of acute exacerbation (5.52±5.18) months. Log-rank showed that the difference between the HP+/AZ group and the HP+/PL group, the HP-/AZ group and the HP-/PL group was statistically significant (P<0.05), but there was no significant difference between the other groups (P>0.05). HP+/AZ group, HP+/PL group, HP-/AZ group, HP-/PL group of patients with COPD, 3 months and 6 months, CRP levels were compared with the basal level was statistically significant (P<0.05); HP+/AZ group of 3 COPD patients and 6 months sTNFR75 level compared with the basic level of the difference was statistically significant (P<0.05). The levels of CRP and sTNFR75 in group HP+/PL, group HP-/AZ and group HP-/PL COPD at 3 months and 6 months were significantly different from those in group HP+/AZ (P<0.05), respectively.Concluson: AZ is effective in preventing COPD exacerbations in patients with HP seropositivity, possibly by modulating TNF pathways related to HP infection.