Sputum Neutrophil Elastase associates with microbiota and P. aeruginosa in bronchiectasis
- 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 and
- Stefano Aliberti1,2
- 1University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy
- 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory unit and Adult Cystic Fibrosis Center, Milan, Italy
- 3Department of Molecular Medicine, University of Pavia, Pavia, Italy
- 4Clinical Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- 5Division of Pulmonary, Critical Care, & Sleep Medicine, New York University School of Medicine, NY
- 6Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Paediatric Highly Intensive Care Unit, Milan, Italy
- 7University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
- Stefano Aliberti, University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory unit and Adult Cystic Fibrosis Center, Milan, Italy. E-mail: stefano.aliberti{at}unimi.it
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 lung microbiome in bronchiectasis is still unexplored. We aimed at understanding if active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics.
Methods An observational, cross-sectional study was conducted at the Bronchiectasis Program 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 through real time PCR and clinical data collected.
Measurements and Main Results Among 185 patients enrolled, decreasing alpha diversity, evaluated through the Shannon entropy (rho: −0.37; p-value <0.00001), Pielou’ evenness (rho: −0.36, p<0.00001) and richness (rho: −0.33; p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon was detected between patients with neutrophil elastase ≥20 µg·mL−1 [3.82 (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 and with Streptococcus in the low elastase group. Further confirmation of the association of P. 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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Gramegna has nothing to disclose.
Conflict of interest: Dr. Sotgiu has nothing to disclose.
Conflict of interest: Sr. SULAIMAN has nothing to disclose.
Conflict of interest: Dr. Chalmers reports grants and personal fees from Glaxosmithkline, grants and personal fees from Insmed, grants and personal fees from Astrazeneca, personal fees from Zambon, grants from Gilead, grants and personal fees from Boehringer ingelheim, grants from Grifols, outside the submitted work.
Conflict of interest: Prof. Marchisio has nothing to disclose.
Conflict of interest: Dr. Oriano has nothing to disclose.
Conflict of interest: Dr. Ruggiero has nothing to disclose.
Conflict of interest: Dr. Terranova has nothing to disclose.
Conflict of interest: Dr. Wu has nothing to disclose.
Conflict of interest: Dr. Blasi reports grants and personal fees from astrazeneca, grants from bayer, grants and personal fees from chiesi, grants and personal fees from gsk, personal fees from guidotti, personal fees from grifols, grants and personal fees from insmed, personal fees from menarini, personal fees from mundipharma, personal fees from novartis, grants and personal fees from pfizer, personal fees from zambon, outside the submitted work.
Conflict of interest: Dr. Saderi has nothing to disclose.
Conflict of interest: L. Segal.
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- Received March 19, 2020.
- Accepted May 19, 2020.
- Copyright ©ERS 2020