Sputum neutrophil elastase associates with microbiota and Pseudomonas aeruginosa in bronchiectasis.

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.
Competing Interests: Conflict of interest: M. Oriano has nothing to disclose. Conflict of interest: A. Gramegna has nothing to disclose. Conflict of interest: L. Terranova has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: I. Sulaiman has nothing to disclose. Conflict of interest: L. Ruggiero has nothing to disclose. Conflict of interest: L. Saderi has nothing to disclose. Conflict of interest: B. Wu has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Insmed, AstraZeneca and Boehringer Ingelheim, personal fees from Zambon, grants from Gilead and Grifols, outside the submitted work. Conflict of interest: L.N. Segal reports personal fees for consultancy from Beyond Air, grants from NIH, outside the submitted work. Conflict of interest: P. Marchisio has nothing to disclose. Conflict of interest: F. Blasi reports grants and personal fees from AstraZeneca, Chiesi, GSK, Insmed and Pfizer, grants from Bayer, personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis and Zambon, outside the submitted work. Conflict of interest: S. Aliberti reports grants and personal fees from Bayer Healthcare, Aradigm Corporation, Grifols, Chiesi and INSMED, personal fees from AstraZeneca, Basilea, Zambon, Novartis, Raptor, Actavis UK Ltd and Horizon, outside the submitted work.
(Copyright ©ERS 2020.)