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吸入性皮质类固醇高、低剂量治疗哮喘患者的气道微生物组。

The airways microbiome of individuals with asthma treated with high and low doses of inhaled corticosteroids.

机构信息

The Asthma Centre, Nottingham Respiratory Research Unit, University of Nottingham, Nottingham City Hospital, Nottingham, United Kingdom.

Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Institute of Pharmaceutical Science, King's College London, London, United Kingdom.

出版信息

PLoS One. 2020 Dec 30;15(12):e0244681. doi: 10.1371/journal.pone.0244681. eCollection 2020.

Abstract

BACKGROUND

Inhaled corticosteroids (ICS) are the mainstay of asthma treatment, but evidence suggests a link between ICS usage and increased rates of respiratory infections. We assessed the composition of the asthmatic airways microbiome in asthma patients taking low and high dose ICS and the stability of the microbiome over a 2 week period.

METHODS

We prospectively recruited 55 individuals with asthma. Of these, 22 were on low-dose ICS and 33 on high-dose ICS (16 on budesonide, 17 on fluticasone propionate). Sputum from each subject underwent DNA extraction, amplification and 16S rRNA gene sequencing of the bacterial component of the microbiome. 19 subjects returned for further sputum induction after 24 h and 2 weeks.

RESULTS

A total of 5,615,037 sequencing reads revealed 167 bacterial taxa in the asthmatic airway samples, with the most abundant being Streptococcus spp. No significant differences in sputum bacterial load or overall community composition were seen between the low- and high-dose ICS groups. However, Streptococcus spp. showed significantly higher relative abundance in subjects taking low-dose ICS (p = 0.002). Haemophilus parainfluenzae was significantly more abundant in subjects on high-dose fluticasone propionate than those on high-dose budesonide (p = 0.047). There were no statistically significant changes in microbiota composition over a 2-week period.

DISCUSSION

Whilst no significant differences were observed between the low- and high-dose ICS groups, increased abundance of the potential pathogen H. parainfluenzae was observed in patients taking high-dose fluticasone propionate compared to those taking high-dose budesonide. The microbiota were stable over fourteen days, providing novel evidence of the established community of bacteria in the asthmatic airways.

CLINICAL TRIAL REGISTRATION

ClinicalTrials.gov NCT02671773.

摘要

背景

吸入性皮质类固醇(ICS)是哮喘治疗的主要手段,但有证据表明 ICS 使用与呼吸道感染率增加之间存在关联。我们评估了使用低剂量和高剂量 ICS 的哮喘患者的哮喘气道微生物组的组成,以及在两周内微生物组的稳定性。

方法

我们前瞻性招募了 55 名哮喘患者。其中,22 名患者使用低剂量 ICS,33 名患者使用高剂量 ICS(16 名使用布地奈德,17 名使用丙酸氟替卡松)。每位受试者的痰液均进行 DNA 提取、扩增和微生物组细菌成分的 16S rRNA 基因测序。19 名受试者在 24 小时和 2 周后返回进行进一步的痰液诱导。

结果

总共 5615037 个测序读数揭示了哮喘气道样本中的 167 种细菌分类群,其中最丰富的是链球菌属。低剂量和高剂量 ICS 组之间的痰液细菌负荷或总体群落组成没有显著差异。然而,在使用低剂量 ICS 的患者中,链球菌属的相对丰度显著更高(p = 0.002)。与使用高剂量布地奈德的患者相比,使用高剂量丙酸氟替卡松的患者中流感嗜血杆菌的丰度显著更高(p = 0.047)。在两周内,微生物组组成没有统计学上的显著变化。

讨论

尽管在低剂量和高剂量 ICS 组之间没有观察到显著差异,但与使用高剂量布地奈德的患者相比,使用高剂量丙酸氟替卡松的患者中潜在病原体流感嗜血杆菌的丰度增加。在十四天内,微生物组是稳定的,为哮喘气道中已建立的细菌群落提供了新的证据。

临床试验注册

ClinicalTrials.gov NCT02671773。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d802/7773270/11a33e5ffbb2/pone.0244681.g001.jpg

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