Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease
Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease
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DOI：
10.1097/cm9.0000000000000677
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发表时间：
2020-03-05
影响因子：
6.1
通讯作者：
He, Zhi-Yi
中科院分区：
文献类型：
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作者：
Qi, Yu-Jing;Sun, Xue-Jiao;He, Zhi-Yi
背景：嗜酸性慢性阻塞性肺疾病（COPD）对皮质类固醇更为敏感。痰微生物组已被证明影响COPD预后，但其在嗜酸性COPD急性加重中的作用尚不清楚。本研究旨在探讨嗜酸性粒细胞性慢阻肺急性加重患者气道微生物组的动态变化。方法：选取2017年6月~ 2018年6月广西医科大学第一附属医院慢性阻塞性肺病急性加重期患者57例，分为两组。外周静脉血嗜酸性粒细胞>= 300个细胞/ μ L的患者分为嗜酸性粒细胞组（Eos），其余为非嗜酸性粒细胞组（Noneos）。所有患者均按照指南接受了包括吸入布地奈德在内的类似治疗。采用16S核糖体RNA （rRNA）法，于治疗第1天和第7天对诱导痰微生物组进行分析。测定血浆中白细胞介素(IL)-6和IL-8的水平，并测定分离的外周血单个核细胞对皮质类固醇的敏感性。两组间定量资料比较采用独立样本t检验或Mann-Whitney U检验。分类资料采用卡方检验或Fisher精确检验进行评价。结果：Eos组26例，Noneos组31例。治疗前，Eos组和Noneos组的α多样性（Shannon指数）（2.65 +/- 0.63 vs. 2.56 +/- 0.54, t = 0.328, P = 0.747）和痰菌群结构相似。处理7 d后，两组α多样性均有所增加，而微生物组丰富度（Ace指数）显著低于Eos组（561.87 +/- 109.13 vs. 767.88 +/- 148.48, t = -3.535, P = 0.002）。同时，Eos组IL-6 （12.09 +/- 2.85 pg/mL vs. 15.54 +/- 2.45 pg/mL, t = -4.913, P < 0.001）和IL-8 （63.64 +/- 21.69 pg/mL vs. 78.97 +/- 17.13 pg/mL, t = -2.981, P = 0.004）降低更为显著，且10(-8)~ 10(-6)mol/L地塞米松浓度下，Eos组IL-8的抑制率显著高于Noneos组（均P < 0.05）。结论：与非Eos患者相比，Eos患者治疗后诱导痰菌群丰富度下降更为明显。较低的血浆炎症因子水平和较高的IL-8抑制百分比可能是由于Eos患者较高的皮质类固醇敏感性。
Background: The eosinophilic chronic obstructive pulmonary disease (COPD) is known to be more sensitive to corticosteroid. The sputum microbiome has been shown to affect COPD prognosis, but its role in acute exacerbations of eosinophilic COPD is unclear. This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD. Methods: Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups. Patients with eosinophils >= 300 cells/mu L in the peripheral venous blood were assigned to the eosinophilic group (Eos) and the rest to the non-eosinophilic group (Noneos). All patients received similar treatment including inhaled budesonide according to the guidelines. The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA (rRNA) method. The levels of interleukin (IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells. Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test. Categorical data were evaluated using Chi-squared test or Fisher's exact test. Results: Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group. Prior to treatment, the alpha diversity (Shannon index) (2.65 +/- 0.63 vs. 2.56 +/- 0.54, t = 0.328, P = 0.747) and the structure of the sputum microbiome were similar in the Eos group and the Noneos group. After 7 days of treatment, alpha diversity increased in both groups, while the microbiome richness (Ace index) was significantly lower in the Eos group (561.87 +/- 109.13 vs. 767.88 +/- 148.48, t = -3.535, P = 0.002). At the same time, IL-6 (12.09 +/- 2.85 pg/mL vs. 15.54 +/- 2.45 pg/mL, t = -4.913, P < 0.001) and IL-8 (63.64 +/- 21.69 pg/mL vs. 78.97 +/- 17.13 pg/mL, t = -2.981, P = 0.004) decreased more significantly in the Eos group, and the percentages of inhibition of IL-8 at dexamethasone concentrations 10(-8) to 10(-6) mol/L were significantly higher in the Eos group than those in the Noneos group (all P < 0.05). Conclusions: The induced sputum microbiome richness decreased more significantly following treatment in the Eos patients compared to the Noneos patients. The lower plasma inflammatory factor levels and the higher percentage of inhibition of IL-8 might be due to higher corticosteroid sensitivity in Eos patients.