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肺部微生物群失调在慢性阻塞性肺疾病急性加重中的影响:皮质类固醇和抗生素治疗的争议性应用以及嗜酸性粒细胞作为疾病标志物的作用。

Influence of the Lung Microbiota Dysbiosis in Chronic Obstructive Pulmonary Disease Exacerbations: The Controversial Use of Corticosteroid and Antibiotic Treatments and the Role of Eosinophils as a Disease Marker.

作者信息

Toraldo Domenico Maurizio, Conte Luana

机构信息

Department of Rehabilitation, Respiratory Care Unit, ASL/Lecce, Italy.

Both authors contributed equally to this manuscript.

出版信息

J Clin Med Res. 2019 Oct;11(10):667-675. doi: 10.14740/jocmr3875. Epub 2019 Oct 4.

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease associated with loss of lung function, poorer quality of life, co-morbidities, significant mortality, and higher health care costs. Frequent acute exacerbations of COPD are sudden worsening of symptoms, the nature of which is associated with bacterial or viral infections. However, one-third of exacerbations remain of undetermined origin. Although it is largely discussed and controversial, current guidelines recommend treatment of exacerbations with bronchodilators, antibiotics, and systemic corticosteroids; this is despite being associated with limited benefits in term of reducing mortality, side effects and without paying attention to the heterogeneity of these exacerbations. Increasing evidence suggests that the lung microbiota plays an important role in COPD and numerous studies have reported differences in the microbiota between healthy and disease states, as well as between exacerbations and stable COPD, leading to the hypothesis that frequent acute exacerbation is more likely to experience significant changes in lung microbiota composition. These findings will need further examination to explain the causes of lung dysbiosis, namely microbial composition, the host response, including the recruitment of eosinophils, lifestyle, diet, cigarette smoking and the use of antibiotics and corticosteroids. It is now important to assess: 1) Whether alterations in the lung microbiota contribute to disease pathogenesis, especially in exacerbations of unknown origin; 2) The role of eosinophils; and 3) Whether the microbiota of the lung can be manipulated therapeutically to improve COPD exacerbation event and disease progression. In summary, we hypothesize that the alterations of the lung microbiota may explain the undetermined origins of exacerbations and that there is an urgent need to facilitate the design of intervention studies that aim at conserving the lung microbial flora.

摘要

慢性阻塞性肺疾病(COPD)是一种使人衰弱的肺部疾病,与肺功能丧失、生活质量较差、合并症、高死亡率以及更高的医疗成本相关。COPD的频繁急性加重是症状的突然恶化,其本质与细菌或病毒感染有关。然而,三分之一的加重病因仍不明确。尽管对此进行了大量讨论且存在争议,但当前指南仍推荐使用支气管扩张剂、抗生素和全身性皮质类固醇治疗加重期;尽管这在降低死亡率方面益处有限,还存在副作用,且未关注这些加重期的异质性。越来越多的证据表明,肺部微生物群在COPD中起重要作用,许多研究报告了健康状态与疾病状态之间以及加重期与稳定期COPD之间微生物群的差异,从而提出了频繁急性加重更可能经历肺部微生物群组成显著变化的假说。这些发现需要进一步研究以解释肺部生态失调的原因,即微生物组成、宿主反应,包括嗜酸性粒细胞的募集、生活方式、饮食、吸烟以及抗生素和皮质类固醇的使用。现在评估以下几点很重要:1)肺部微生物群的改变是否有助于疾病发病机制,尤其是在病因不明的加重期;2)嗜酸性粒细胞的作用;3)肺部微生物群是否可以通过治疗手段进行调控以改善COPD加重事件和疾病进展。总之,我们假设肺部微生物群的改变可能解释加重期病因不明的情况,并且迫切需要推动旨在保护肺部微生物群落的干预研究设计。

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