摘要

     背景：
     抗生素耐药性是一个重大的全球威胁。我们假设慢性阻塞性肺疾病（COPD）气道是一个与COPD微生物群相关的耐药基因（ARGs）库。
     目标：
     目的探讨慢性阻塞性肺病（COPD）患者和健康志愿者呼吸道标本的耐药基因谱。
     方法：
     以279个特异性ARGs为靶点的定量PCR检测了稳定期、加重期和恢复期（n=55；COPD-BEAT研究）COPD患者痰中的抗药性，在过去12个月内（超过研究）暴露于抗生素（n=7）或未暴露于抗生素（n=22）的健康对照组，以及来自COPD（n=8）和健康对照组（n=7）的支气管灌洗样本（EvA研究）。
      结果：
      稳定型COPD患者（35.2（1.6））的ARG平均（SEM）患病率高于健康对照组（27.6（1.7）；p=0.004），且与总细菌丰度相关（r2=0.23；p<0.001）。ARG阳性信号在COPD患者中的流行与COPD症状、肺功能及病情恶化时的变化无关。在COPD的高γ蛋白菌和高硬度组中，ARG的患病率在稳定状态下没有差异，但在稳定状态下，ARG的患病率从稳定到恶化到恢复显著下降（p=0.011），而细菌总数没有变化。在过去12个月内，COPD与健康、COPD微生物群亚群、痰和支气管镜检样本的ARG模式相似，与抗生素暴露无关。
      结论：
      ARGs在痰中高度流行，与健康人和COPD患者的细菌丰度大致成比例。因此，慢性阻塞性肺病似乎是一个精氨酸水库，由于高水平的细菌殖民。

BACKGROUND:

Antibiotic resistance is a major global threat. We hypothesised that the chronic obstructive pulmonary disease (COPD) airway is a reservoir of antimicrobial resistance genes (ARGs) that associate with microbiome-specific COPD subgroups.

OBJECTIVE:

To determine the resistance gene profiles in respiratory samples from COPD patients and healthy volunteers.

METHODS:

Quantitative PCR targeting 279 specific ARGs was used to profile the resistomes in sputum from subjects with COPD at stable, exacerbation and recovery visits (n=55; COPD-BEAT study), healthy controls with (n=7) or without (n=22) exposure to antibiotics in the preceding 12 months (EXCEED study) and in bronchial brush samples from COPD (n=8) and healthy controls (n=7) (EvA study).

RESULTS:

ARG mean (SEM) prevalence was greater in stable COPD samples (35.2 (1.6)) than in healthy controls (27.6 (1.7); p=0.004) and correlated with total bacterial abundance (r²=0.23; p<0.001). Prevalence of ARG positive signals in individuals was not related to COPD symptoms, lung function or their changes at exacerbation. In the COPD subgroups designated High γProteobacteria and High Firmicutes, ARG prevalence was not different at stable state but significantly declined from stable through exacerbation to recovery in the former (p=0.011) without changes in total bacterial abundance. The ARG patterns were similar in COPD versus health, COPD microbiome-subgroups and between sputum and bronchoscopic samples independent of antibiotic exposure in the last 12 months.

CONCLUSIONS:

ARGs are highly prevalent in sputum, broadly in proportion to bacterial abundance in both healthy and COPD subjects. Thus, COPD appears to be an ARG reservoir due to high levels of bacterial colonisation.

       https://thorax.bmj.com/content/75/1/8.long