Oriano Martina, Gramegna Andrea, Terranova Leonardo, Sotgiu Giovanni, Sulaiman Imran, Ruggiero Luca, Saderi Laura, Wu Benjamin, Chalmers James D, Segal Leopoldo N, Marchisio Paola, Blasi Francesco, Aliberti Stefano
University of Milan, Dept of Pathophysiology and Transplantation, Milan, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Dept, Respiratory Unit and Adult Cystic Fibrosis Center, Milan, Italy.
Eur Respir J. 2020 Oct 22;56(4). doi: 10.1183/13993003.00769-2020. Print 2020 Oct.
Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics.
An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected.
Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ -0.37, p<0.00001) and Pielou's evenness (ρ -0.36, p<0.00001) and richness (ρ -0.33, p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL (median 3.82, interquartile range 2.20-4.96) neutrophil elastase <20 µg·mL (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with in the high-elastase group and with in the low-elastase group. Further confirmation of the association of with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR.
High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to infection.
中性粒细胞炎症是支气管扩张病理生理学的主要驱动因素，中性粒细胞弹性蛋白酶活性是迄今为止在痰液中评估的最有前景的生物标志物。在支气管扩张中，活性中性粒细胞弹性蛋白酶与肺部微生物群之间的关系仍未得到探索。我们旨在了解活性中性粒细胞弹性蛋白酶是否与低微生物多样性和独特的微生物群特征相关。
在意大利米兰综合医院的支气管扩张项目中进行了一项观察性横断面研究，2017年3月至2019年3月期间纳入了成年支气管扩张患者。在稳定状态下收集痰液，测量活性中性粒细胞弹性蛋白酶，通过16S rRNA基因测序分析微生物群，通过实时PCR进行呼吸道病原体的分子评估，并收集临床数据。
在纳入的185例患者中，通过香农熵（ρ -0.37，p<0.00001）、皮洛均匀度（ρ -0.36，p<0.00001）和丰富度（ρ -0.33，p<0.00001）评估的α多样性降低与弹性蛋白酶升高显著相关。中性粒细胞弹性蛋白酶≥20μg·mL的患者（中位数3.82，四分位间距2.20 - 4.96）与中性粒细胞弹性蛋白酶<20μg·mL的患者（4.88，3.68 - 5.80；p<0.0001）之间检测到的香农熵中位数水平存在显著差异。在这两组中发现了不同的微生物群，主要特征是高弹性蛋白酶组中 富集，低弹性蛋白酶组中 富集。基于标准培养和靶向实时PCR进一步证实了 与活性中性粒细胞弹性蛋白酶升高的关联。
高水平的活性中性粒细胞弹性蛋白酶与低微生物群多样性相关，特别是与 感染相关。
