Martina Oriano1,2,3, Andrea Gramegna1,2, Leonardo Terranova1,2, Giovanni Sotgiu4, Imran Sulaiman5, Luca Ruggiero6, Laura Saderi4, Benjamin Wu5, James D Chalmers7, Leopoldo N Segal5, Paola Marchisio1,6, Francesco Blasi1,2, Stefano Aliberti1,2. 1. University of Milan, Dept of Pathophysiology and Transplantation, Milan, Italy. 2. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine Dept, Respiratory Unit and Adult Cystic Fibrosis Center, Milan, Italy. 3. Dept of Molecular Medicine, University of Pavia, Pavia, Italy. 4. Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari, Sassari, Italy. 5. Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, NY, USA. 6. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Paediatric Highly Intensive Care Unit, Milan, Italy. 7. University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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-1 (median 3.82, interquartile range 2.20-4.96) versus neutrophil elastase <20 µg·mL-1 (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR. CONCLUSIONS: High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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-1 (median 3.82, interquartile range 2.20-4.96) versus neutrophil elastase <20 µg·mL-1 (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR. CONCLUSIONS: High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection.
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Authors: Martina Oriano; Francesco Amati; Andrea Gramegna; Anthony De Soyza; Marco Mantero; Oriol Sibila; Sanjay H Chotirmall; Antonio Voza; Paola Marchisio; Francesco Blasi; Stefano Aliberti Journal: Int J Mol Sci Date: 2021-06-01 Impact factor: 5.923