Department of Respiratory Medicine, Galway University Hospital, Newcastle Road, Galway, Ireland.
Department of Respiratory Medicine, Cork University Hospital, Galway, Ireland.
Respir Res. 2022 Mar 14;23(1):58. doi: 10.1186/s12931-022-01947-5.
Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators.
There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies.
Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
尽管 COPD 患者遵循 GOLD 指南 D 级推荐治疗方案，但仍有许多患者病情恶化。急性加重会导致症状加重、肺功能下降和死亡率增加。本综述的目的是检索任何针对 GOLD 级 D 类患者的预防性抗菌治疗试验，这些患者对推荐治疗“失败”，并讨论 COPD 表型、肺和肠道微生物群以及合并症在制定针对高频急性加重患者的抗菌治疗方案中的作用。
迄今为止，发表的文献中缺乏大型、精心设计的研究。单中心、研究设计、缺乏明确的对照组、入组患者数量不足和随访时间短等因素是许多研究的重要限制因素。一项涉及 1000 多名患者的安慰剂对照研究显示，这些患者在前一年中有 2 次或更多次中度加重，与安慰剂相比，5 天疗程的莫西沙星（moxifloxacillin）重复治疗（间隔 8 周）可使加重减少 19%，但结果无统计学意义。在铜绿假单胞菌（Pa）定植的 COPD 患者中，使用妥布霉素、多粘菌素和庆大霉素进行吸入性抗菌治疗可显著降低加重的频率。病毒常导致 COPD（AECOPD）急性加重，无论是作为原发性感染因子还是作为协同因子。然而，除了流感疫苗接种外，没有抗病毒治疗试验能对减少 AECOPD 产生积极影响。确定影响加重频率和严重程度的临床表型和共存条件对于提供个体化治疗和靶向治疗至关重要。肺部和肠道微生物群的作用越来越受到重视，鉴定致病细菌可能在个体化抗菌治疗中发挥重要作用。
尽管患者遵循指南指导的治疗方案，但仍有抗菌治疗选择有限。对患者进行表型分析、确定共存条件和评估微生物群是个体化抗菌治疗的关键。鉴于病毒对 AECOPD 的影响，抗病毒治疗药物和靶向抗病毒疫苗应成为未来研究的重点。
