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.

中文翻译：

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来自 COPD 和健康受试者的痰的抗性分析揭示了目标基因的细菌负荷相关流行

背景抗生素耐药性是一个主要的全球威胁。我们假设慢性阻塞性肺疾病 (COPD) 气道是与微生物组特异性 COPD 亚组相关的抗菌素耐药基因 (ARG) 的储存库。目的确定COPD患者和健康志愿者呼吸道样本中的耐药基因谱。方法 使用针对 279 个特定 ARG 的定量 PCR 来分析 COPD 患者在稳定、恶化和恢复就诊（n = 55；COPD-BEAT 研究）、有（n = 7）或没有（n = 22) 在前 12 个月（EXCEED 研究）和来自 COPD（n=8）和健康对照（n=7）（EvA 研究）的支气管刷样本中暴露于抗生素。结果在稳定的 COPD 样本中，ARG 平均值 (SEM) 患病率更高 (35.2 (1. 6)) 高于健康对照 (27.6 (1.7)；p=0.004) 并与总细菌丰度相关 (r2=0.23；p<0.001)。个体中 ARG 阳性信号的流行与 COPD 症状、肺功能或其恶化时的变化无关。在指定为高 γProteobacteria 和 High Firmicutes 的 COPD 亚组中，ARG 患病率在稳定状态下没有差异，但在前者中从稳定到恶化到恢复显着下降 (p=0.011)，而总细菌丰度没有变化。在过去 12 个月内，COPD 与健康、COPD 微生物组亚组以及痰和支气管镜样本之间的 ARG 模式相似，与抗生素暴露无关。结论 ARGs 在痰液中高度流行，与健康和 COPD 受试者的细菌丰度大致成正比。因此，