幽门螺旋杆菌感染与稳定期慢性阻塞性肺疾病患者病情及预后的关系

Correlation between Helicobacter pylori infection and disease condition and prognosis of stable chronic obstructive pulmonary disease

目的研究稳定期慢性阻塞性肺疾病(简称慢阻肺)患者幽门螺旋杆菌(HP)感染与病情及预后的关系。方法本研究为队列研究。采用非随机抽样法,选择2018年1月至2020年9月期间柳州市人民医院收治的120例稳定期慢阻肺患者,采用14C尿素呼气试验检测HP放射性计数,≥100 dpm/mmol的患者为HP阳性组(48例),<100 dpm/mmol的患者为HP阴性组(72例)。另取50名一般资料与慢阻肺患者匹配的健康志愿者作为对照组。采用肺功能仪检测第1秒用力呼气容积(FEV1)/用力肺活量(FVC)及FEV1%pred,采用荧光定量聚合酶链反应检测外周血核因子κB(NF-κB)的mRNA表达水平,采用酶联免疫吸附法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)的含量,随访慢阻肺患者的急性加重情况。结果HP阳性组患者的FEV1%pred、FEV1/FVC分别为(57.10±9.99)%、(51.69±11.45)%,均低于对照组及HP阴性组(均P<0.05)。HP阳性组外周血NF-κB mRNA表达水平及血清TNF-α、IL-1β、ICAM-1的含量分别为1.43±0.27、(29.67±6.05)μg/L、(6.75±1.24)μg/L、(351.20±85.17)μg/L,均高于对照组及HP阴性组(均P<0.05)。HP阳性组中HP放射性计数与FEV1%pred、FEV1/FVC呈负相关(r值分别为-0.40、-0.33,均P<0.05),与外周血NF-κB mRNA表达水平及血清TNF-α、IL-1β、ICAM-1含量呈正相关(r值分别为0.48、0.48、0.43、0.46,均P<0.05)。经K-M曲线分析,HP阳性组的未急性加重率低于HP阴性组(χ2=4.76,P<0.05);经受试者工作特征曲线分析,HP放射性计数对稳定期慢阻肺患者急性加重具有预测价值,预测的曲线下面积为0.731,95%CI为0.628~0.833,敏感度、特异度分别为75.61%和76.47%。结论HP感染与稳定期慢阻肺患者肺功能减退、炎症反应激活、急性加重的发生风险增加有关,检测HP放射性计数对预后具有预测价值。

Objective To identify the correlation between Helicobacter pylori(H.pylori)infection and the condition and prognosis of stable chronic obstructive pulmonary disease(COPD).Methods It was a retrospective cohort study involving 120 patients with stable COPD admitted in Liuzhou People′s Hospital who were non-randomly enrolled from January 2018 to September 2020.The radioactive carbon count was measured by 14C urea breath test for diagnosing H.pylori infection.Patients with the radioactive carbon count≥100 dpm/mmol were enrolled in H.pylori-positive group(n=48),and those with the radioactive carbon count<100 dpm/mmol were enrolled in H.pylori-negative group(n=72).Another 50 healthy volunteers age-matched with COPD patients were selected as control group.FEV1/FVC(the forced expiratory volume in one second/forced vital capacity)and FEV1%pred(a derived value of FEV1%)were measured by a pulmonary function analyzer.The expression of nuclear factor-κB(NF-κB)mRNA in peripheral blood was detected by Real time-quantitative PCR(RT-qPCR)technology.The contents of TNF-α,IL-1βand ICAM-1 were detected by Enzyme-linked immunosorbent assay(ELISA).The acute exacerbation of COPD was followed up.Results FEV1%pred and FEV1/FVC in H.pylori-positive group were(57.10±9.99)%and(51.69±11.45)%,which were significantly lower than those in control group and H.pylori-negative group(all P<0.05).The expression level of NF-κB mRNA and the contents of serum TNF-α,IL-1β,and ICAM-1 were 1.43±0.27,(29.67±6.05)μg/L,(6.75±1.24)μg/L,and(351.20±85.17)μg/L,respectively,which were significantly higher than those of control group and H.pylori-negative group(all P<0.05).In H.pylori-positive group,the radioactive carbon count was negatively correlated with FEV1%pred(r=-0.40),and FEV1/FVC(r=-0.33),but positively correlated with the expression level of NF-κB mRNA(r=0.48),TNF-α(r=0.48),IL-1β(r=0.43),and ICAM-1(r=0.46)(all P<0.05).Kaplan-Meier survival curve analysis showed that the non-acute exacerbation rate and cumulative survival rate in H.pylori-positive group were significantly lower than those of H.pylori-negative group(both P<0.05).ROC curves visualized that the radioactive carbon count in 14C urea breath test had a predictive value for the acute exacerbation and survival of stable COPD patients,with the predicted area under the curve of 0.731(95%CI:0.628-0.833),and the sensitivity and specificity of 75.61%and 76.47%,respectively.Conclusions H.pylori infection is significantly correlated with the decreasing pulmonary function,activation of inflammatory reaction,and increasing risk of acute exacerbation.Detection of the radioactive carbon count in 14C urea breath test has a predictive value for the prognosis of stable COPD.